Severe combined immunodeficiency in children: possible causes, symptoms and treatments. Severe combined immunodeficiency. X-linked type

Severe combined immunodeficiencies (SCID, SCID) - a group of primary immunodeficiencies. In SCID, as a result of one or another genetic disorder, the production and/or functioning of both B-lymphocytes and T-lymphocytes is severely impaired. Accordingly, both main types of immunity are undermined: both the production of antibodies, for which B-lymphocytes are “responsible”, and cellular immunity, in which key role played by T lymphocytes. From birth, patients are practically defenseless against infections, and until recently the only way to prolong their lives was to keep them in a completely sterile environment.

There are a number of types of SCID.
* X-linked severe combined immunodeficiency(X-SCID) – the most common SCID (about 50% of all cases). The body produces B lymphocytes that are unable to function normally; however, the number of T-lymphocytes is very small.
* Adenosine deaminase deficiency(about 15% of SCID cases) is a serious disorder of the immune system. With this disease, there is an accumulation of substances leading to the destruction of lymphocytes; There is a deficiency of mature B and T lymphocytes in the blood, especially the latter.
* Omenn syndrome- a disease in which the level of B lymphocytes is sharply reduced and T lymphocytes function abnormally, causing symptoms similar to an autoimmune disease or graft-versus-host disease.
*Other types of SCID are known, including reticular dysgenesis(in the blood there is a deficiency of not only lymphocytes, but also other leukocytes - monocytes and neutrophils), naked lymphocyte syndrome and etc.

Incidence and risk factors

The total incidence of SCID is about 1-2 cases per 100 thousand newborns. It may be elevated in communities where consanguineous marriages are common.

All SCID are hereditary diseases. As the name suggests, the inheritance of X-linked SCID is X-linked recessive. This means that the disease occurs exclusively in boys, but is inherited from the mother, who is clinically healthy, but is a carrier of the “defective” gene. In the sons of such a carrier woman, the probability of the disease is 50%. The inheritance of the remaining SCID is autosomal recessive, that is, a child (boy or girl) can be born sick only if both the father and mother are carriers of the genetic defect; the probability of having a sick child is 25%.

For families who have already had children with SCID, consultation with a geneticist is recommended.

Signs and symptoms

Manifestations of SCID are primarily associated with immune disorders. Children experience constant severe infections from the very first months of life: chronic diarrhea, inflammation of the lungs (pneumonia caused by protozoa - pneumocystis is especially typical), severe fungal infections (candidiasis of the skin and mucous membranes, especially the oral cavity), inflammation of the ear, manifestations of herpes, etc. Children grow slowly and gain weight poorly; their appetite is reduced and their temperature is often elevated.

For some types of SCID, such as Omenn's syndrome, symptoms similar to graft-versus-host disease (GVHD) may also occur, such as rash, redness, and peeling of the skin.

Diagnostics

If a child, from the first months of life, constantly experiences severe infections that threaten his life and prevent him from growing and developing, then this is a reason to assume congenital immunodeficiency, including, possibly, SCID. Particularly typical for SCID are pneumonia caused by pneumocystis ( Pneumocystis jiroveci), and severe fungal infections of the mucous membranes - candidiasis (thrush, moniliasis).

Laboratory diagnosis of SCID involves measuring the levels of various lymphocytes and antibodies in the blood. Molecular genetic testing can be used to detect a specific genetic defect. Other studies are also being carried out.

Since it is advisable to begin treatment of children with SCID as early as possible, the introduction of screening programs for all newborns is being discussed in the United States. There is a relatively simple test for the presence of specific substances (by-products of T-lymphocyte maturation - so-called TREC), which in many cases can distinguish between healthy newborns and children with SCID. However, this technique has not yet been fully developed.

Treatment

Once a child is diagnosed with SCID, treatment must begin immediately. Patients are given intravenous immunoglobulin and medications are used to treat and prevent infections. In addition, in order to avoid infection with any infectious diseases, the patient is kept in an isolated sterile box.

However, these are all only temporary measures that allow for some time to avoid a sharp deterioration in the patient’s condition. For most forms of SCID, including the X-linked form, Omenn syndrome, etc., the main treatment method is bone marrow transplantation, and it is advisable to do it as early as possible. The donor's bone marrow will restore normal hematopoiesis, and functional lymphocytes will appear in the blood. If the production of antibodies by B lymphocytes is insufficient even after transplantation, intravenous infusions of immunoglobulin can be used.

In transplantations for SCID, one of the parents relatively often becomes the bone marrow donor (haploidentical transplantation). The type of conditioning depends on the disease; in some forms of SCID, transplantation is possible without intensive preliminary chemotherapy, since the patient’s body is not capable of rejecting the transplant due to its very low own immunity.

Standing somewhat apart is this form of SCID, such as adenosine deaminase deficiency: Here the main form of treatment is replacement therapy with this enzyme. Bone marrow transplantation is also possible. There are examples of successful use of gene therapy. Clinical trials of gene therapy are also underway. X-linked SCID.

It must be remembered that vaccination with “live” vaccines is contraindicated for patients with SCID: for example, BCG vaccination administered in a maternity hospital can cause a severe systemic disease.

Forecast

Without treatment, children born with one or another SCID usually die within the first 1-2 years of life (in some forms of the disease, within the first months). However, bone marrow transplantation, if successful, leads to recovery. The proportion of successful transplantations in these patients is quite high, especially if their general condition before transplantation was quite safe: up to 80% of children recover. If B-lymphocyte function (antibody production) remains insufficient after transplantation, intravenous immunoglobulins may be administered.

Specific defect. Impaired differentiation of stem cells into B and T lymphocytes. Autosomal recessive type. Specific defect. Mutation of the tyrosine kinase gene ZAP-70, a signal transducer in T-lymphocytes necessary for their proliferation. Characteristic absence of CD8+ cells in peripheral blood. Clinical features. Recurrent infectious diseases, emaciation, developmental delay. Lymphopenia and hypoplasia of the thymus are characteristic. The number and function of T lymphocytes are reduced. Hypogammaglobulinemia, decreased level of B-lymphocytes. Skin tests and antibody production are reduced. Patients die in the first 1-2 years of life from a viral, bacterial, protozoal infection or mycosis.

Louis-Bar syndrome, ataxia - telangiectasia with an autosomal recessive type of inheritance.Specific defect. Dysfunction of T- and B-lymphocytes. The level of Ig A, Ig E and IgG is reduced. Hypoplasia of the thymus, spleen, lymph nodes, tonsils. Clinical features. Telangiectasia of the skin and eyes; progressive cerebellar ataxia; recurrent infection of the paranasal sinuses and lungs of a viral and bacterial nature; bronchiectasis; increased alpha-fetoprotein levels. In the long term - damage to the nervous, endocrine, vascular systems, malignant tumors. The disease is most often diagnosed at 5-7 years of age, equally often in boys and girls. Half of the patients have mental retardation, adynamia, and limited interests. Some patients live up to 20 or even 40 years.

Wiskott-Aldrich syndrome ( SVO, ID is linked to the X chromosome ) - primary immunodeficiency state of the X-linked type, manifested by a triad of symptoms that are determined in boys from an early age: 1) increased susceptibility to infectious diseases (frequent acute respiratory infections, bronchopulmonary infections, infections of the ENT organs, skin, mucous membranes, urinary tract and gastrointestinal tract); 2) hemorrhagic syndrome caused by thrombocytopenia; 3). atopic dermatitis and eczema. Specific defect. Activation of CD4+ and CD8+ cells is impaired. Impaired production of IgM to capsular bacteria (pneumococci). IgG level is normal. The level of IgA and IgE is increased. Isohemagglutinins are reduced or absent. The number of B lymphocytes is usually normal. Clinical features. The first manifestations are possible from 2 to 5 months of age, a triad is observed - eczema, thrombocytopenia, frequent pyogenic infectious diseases. Subsequently develop autoimmune diseases, malignant neoplasms, hemorrhagic syndrome (melena, purpura, nosebleeds). With age, the condition may stabilize.

Nymegen syndrome is a form of combined immunodeficiency endemic to Ukraine. An autosomal recessive type of inheritance is characteristic - a mutation of a gene that is located on chromosome 8. Impaired repair leads to the accumulation of DNA damage. Children with Nymegen syndrome are often of Slavic origin. Clinical picture: microcephaly, which progresses with age. Brain damage: subarachnoid cysts, agenesis of the corpus callosum, hydrocephalus; “bird-like” face - low forehead, prominent cheekbones, large nose, relatively large and dysplastic ears. Delayed physical development, delayed formation of secondary sexual characteristics, mental retardation. Disturbance of pigmentation in the form of “café au lait” spots. Sometimes telengectasia, pigmented nevi, capillary or cavernous hemangiomas. Premature gray hair. Anomalies in the development of other systems. Recurrent infections respiratory tract, from the formation of bronchiectasis. The cause of death was malignant tumors: lymphoma, acute lymphoblastic leukemia, lymphogranulomatosis. primary immunodeficiency genetic complement

Immunodeficiency with elevated levels of immunoglobulin M (X-linked). An X-linked form of immune deficiency with CD40 ligand abnormality and hyperimmunoglobulinemia M is a combined primary immunodeficiency. Specific defect. Absence of CD40 ligand on T helper cells. Interaction T and B lymphocytes due to the contact of CD40 ligand - CD40 molecules, this is a critical event necessary for the switch of B cells from IgM synthesis to the synthesis of immunoglobulins of other isotypes and the formation of plasma cell clones of appropriate specificity. Low levels IgG, Ho and E. Clinical features. Boys are sick. Characteristic recurrent bacterial infections, increased frequency of opportunistic infections, in particular due to Pneumocystis carinii.

Good's syndrome is a severe combined immunodeficiency disorder. The inheritance type has not been established. Histologically - delayed development of the thymus. Clinical picture: recurrent bacterial, viral and fungal infections; tendency to malignant tumors.

Metaphyseal chondrodysplasia McC-Uzik (short-legged dwarf syndrome, cartilaginous-hairy hypoplasia syndrome). Immunodeficiency with short-legged dwarf syndrome is characterized by an autosomal recessive type of inheritance. Clinical features: disproportionate physique from the moment of birth, limbs are short and thick, short stature, pronounced around the neck and limbs skin folds, small teeth, irregular shape, flattening of vertebral bodies, lumbar lordosis, flattening chest, curvature of the lower ribs outward, curvature lower limbs, joint hypermobility, which is accompanied by an increase in range of motion, defects in hair formation. Intestinal malabsorption syndrome, celiac disease, recurrent infectious diseases.

Chediak-Steinbrink-Higashi syndrome. Specific defect. Neutrophils lose the ability to release lysosomal enzymes while maintaining the ability to fuse phagosomes and lysosomes. Violation of chemotaxis. Clinical features. It is characterized by albinism, photosensitivity of the skin and severe recurrent pyogenic infections, which are caused primarily by streptococci and staphylococci. In such patients, neutrophils contain giant lysosomes, which retain the ability to fuse with phagosomes, but lose the ability to release the enzymes they contain. As a consequence of this, a violation of the digestive ability of microorganisms develops.

Hyperimmunoglobulinemia E syndrome (Job syndrome). Specific defect. Reduced production of interferon gamma by T-helper type 1. Increased production of IgE >1000 IU/ML in the presence of a history of dermatitis and repeated deep purulent infections with a “cold” course; histamine is released which disrupts neutrophil chemotaxis. Clinical features. It is characterized by recurrent, so-called cold abscesses of the skin and subcutaneous tissue, lymph nodes, repeated purulent otitis media with a cold course, and chronic eczema. Abscesses are called cold abscesses due to the lack of a normal inflammatory response. Severe episodes are especially dangerous acute pneumonia, incl. destructive (in 50%) with the outcome in pneumocele (in 50%), liver abscesses. Characteristic somatic signs are atypical “ atopic dermatitis”, dysplastic facial features, spontaneous fractures of tubular bones (Table 8).

Experience in treating patients with primary immunodeficiencies has made it possible to establish the existence of certain associations between the type of immunodeficiency, the pathogen and clinical manifestations. Deficiency of the humoral and phagocytic immune systems is characterized by the presence of extracellular bacterial infection, and for a deficiency of cellular immunity - intracellular bacterial infection, as well as viral, protozoal infection and mycosis.

Physiological immunodeficiency of early childhood The imperfection of the immune system in children in the first years (especially the first months) of life has become the reason for the identification of physiological immunodeficiency in early childhood, which affects, to one degree or another, all parts of the immune system.

It has been established that maternal malnutrition during intrauterine development the fetus leads to disruption of the development of the immune system (primarily this is reflected in the size and functions of the thymus), which after birth and in adulthood can cause negative consequences for a person.

During the period of fetal development beyond 22 weeks of gestation, under the influence of maternal food allergens, the embryo may develop sensitization, which may in the future turn out to be atopic reactions to this particular allergen.

During the period of early postnatal maturation, the child’s immune system is under the beneficial influence of breast milk, which contains, in addition to essential nutrients, various cytokines and hormones that control the proper development of the newborn’s immune system. These include, in particular, prolactin. A lack of vitamins, mineral salts, trace elements and antioxidants in the mother’s diet during this period can lead to the development of a deficiency of the newborn’s immune system.

In the period after weaning, under the influence of food products, polarization of the function of T-helper types 1 and 2 occurs, tolerance to food products develops, and the basis for the manifestations of atopy is laid.

Deficiency of components of the complement system. Primary deficiency of components of the complement system is less common than other primary immunodeficiencies: their frequency is only 1% of the total number of primary immunodeficiencies. Genetic defects have been described for most complement components - Clq, Clr, Cls, C2, C4, C3, C5, C6, C7, C8 and C9. All of them are inherited in an autosomal recessive manner; heterozygotes can be detected during laboratory examination: their level of defective complement protein is reduced by half compared to the norm. The most common deficiency in the human population is C2: approximately one in 100 people is heterozygous for a defect in this protein. Clq deficiency is most common in Japanese ethnicity, with approximately one in fifty being heterozygous. The most common clinical symptom associated with defects in early complement components (C1, C2, C4) is immune complex disease. While congenital defects of late complement components (C5 to C8) are associated with recurrent gonococcal infection. SZ deficiency clinically appears to be a recurrent pyogenic infection. Thus, the clinical and immunological associations found confirm the importance of the complement system: 1) in the elimination and/or solubilization (destruction) of immune complexes; 2) in antibacterial protection; 3) in the mechanisms of opsonization. Clinically important are also congenital defects of complement system inhibitors: C1-inhibitor and C3b-inactivator (factor I). C1 inhibitor deficiency clinically appears to be congenital angioedema. Inherited in an autosomal dominant manner. Such patients are prone to recurrent attacks of subcutaneous edema, which can be localized in any part of the body. Table 5 shows the clinical manifestations associated with deficiency of various complement components.

Congenital angioedema One clinical example of a primary defect in the complement system is congenital angioedema caused by a deficiency of the inhibitor of the first complement component, C1-inhibitor (C1-ing). This disease is inherited in an autosomal dominant manner. The main clinical symptom of the disease is recurrent swelling of the skin and mucous membranes without signs of inflammation. The most common localization of edema: limbs, face, mucous membrane of the oral cavity, stomach and intestines. pharynx (pharynx), larynx. Clinical features congenital form of angioedema, distinguishing it from the allergic form of such edema: 1) limited area; 2) dense consistency; 3) white color; 4) relative painlessness when localized in the skin; pain, nausea and diarrhea due to swelling of the mucous membrane of the stomach and intestines; 5) absence of itching; 6) the rare presence of a maculopapular and erythematous rash that does not itch; 7) lack of association with urticaria.

Swelling of the mucous membrane of the intestines can cause obstruction, and swelling of the mucous membrane of the upper respiratory tract can lead to asphyxia.

Factors that provoke the development of edema include: 1) trauma: a) manipulation of teeth; b) tonsillectomy; c) endotracheal manipulations; d) accidental injury; 2) physical stress; 3) menstruation; 4) pregnancy; 5) emotional shock; 6) anxiety, stress. In 1/3 of the cases causal factors the development of edema has not been established. Quite often, patients indicate that several hours before the development of edema in this place, they feel a stabbing or sensation of compression.

The duration of angioedema is usually 24-72 hours. This feature can also be used to differential diagnosis with allergic angioedema, which is characterized by faster disappearance.

The incidence of edema varies among patients. Some patients do not have edema for several years, but after this they can experience it repeatedly for a short time. In others, edema develops constantly. Interestingly, angioedema does not develop in the last two trimesters of pregnancy and during childbirth.

Severe combined immunodeficiency

Severe combined immunodeficiency (SCID), (also known as alymphocytosis, Glyantsman-Riniker syndrome, severe combined immunodeficiency syndrome, and thymic alymphoplasia) is a genetic disease in which both types of "weapons" (B-lymphocytes and T-lymphocytes) of the adaptive immune system are damaged as a result of a defect in one from several possible genes. SCID is a severe form of hereditary immunodeficiency. SCID is also known as boy in a bubble syndrome, since patients are extremely vulnerable to infectious diseases and are forced to stay in a sterile environment. One of these patients was David Vetter. SCID is the result of such damage to the immune system that it is considered virtually non-existent.

Symptoms of SCID may include chronic diarrhea, ear infections, recurrent pneumocystosis, abundant oral candidiasis. Without treatment, unless a successful hematopoietic stem cell transplant has been performed, children with SCID usually die within the first year of life from severe recurrent infections.

Prevalence

The most commonly cited prevalence rate for SCID is approximately 1 in 100,000 births, although this is considered by some to be an underestimation of the true prevalence. In Australia, the incidence is reported as 1 in 65,000 births.

Recent studies have shown that in the Navajo population, 1 in every 2,500 children will inherit severe combined immunodeficiency. This is the cause of a significant percentage of morbidity and mortality among children of this nationality. Current research has revealed a similar pattern among the Apache tribes.

Types

Detection

Several US states are conducting pilot studies to diagnose SCID in newborns using recombinant T-lymphocyte excision. As of February 1, 2009, newborn screening for SCID is being conducted in Wisconsin and Massachusetts. SCID screening began in Michigan in October 2011. However, standardized testing for SCID is currently unavailable due to the diversity of the genetic defect in newborns. Some forms of SCID can be detected by sequencing fetal DNA if the condition is suspected. Otherwise, SCID is not diagnosed until approximately 6 months. As a rule, its presence can be indicated by recurrent infections. The delay in detection of SCID is due to the fact that maternal antibodies are present in newborns during the first few weeks of life, and children with SCID appear healthy.

Treatment

The most common treatment for SCID is hematopoietic stem cell transplantation, which is successful either with an unrelated donor or with a semi-matched donor, which can be one of the parents. The latest type of transplantation is called “haploidentical” and was improved at Memorial cancer center them. Sloan-Kettering in New York, as well as at Duke University Medical Center, where the greatest number similar transplants. In haploidentical bone marrow transplantation, donor bone marrow is required to avoid a homologous reaction when all mature T cells are used. Consequently, immune system functionality takes longer to develop in a patient receiving bone marrow. David Vetter, one of the first to undergo such an operation, eventually died from the Epstein-Barr virus, which infected the bone marrow transplanted from his sister. Today, transplants performed in the first 3 months of a child’s life have a high success rate. Doctors have also successfully performed intrauterine transplants done before the baby was born using umbilical cord blood rich in stem cells. Intrauterine transplantation allows the fetal immune system to develop in the sterile environment of the uterus. However, such a complication as a homologous disease is quite difficult to detect. More recently, gene therapy has been proposed as an alternative to bone marrow transplantation. In 1990, 4-year-old Ashanti de Silva became the first patient to successfully undergo gene therapy. The researchers collected Ashanti blood samples, isolated some of the white blood cells, and then used a virus to insert healthy adenosine deaminases (ADAs) into them. These cells were then reintroduced and began producing the normal enzyme. ADA deficiency was compensated by additional weekly injections. However, the tests were stopped. In 2000, it was discovered that 2 out of 10 patients with gene therapy developed leukemia as a result of the introduction of a gene carrying a retrovirus near an oncogene. In 2007, 4 out of 10 patients were also diagnosed with leukemia. Currently, work in the field of gene therapy is aimed at changing the viral vector to reduce the likelihood of tumorigenesis.

There are also some non-medical treatments for SCID. Reverse isolation involves the use of laminar air flow and mechanical barriers (to avoid physical contact with other people) to isolate the patient from any harmful pathogenic microorganisms, present in external environment.

Notes

1. Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0
2. NEWBORN SCREENING FOR PRIMARY IMMUNODEFICIENCY DISEASE
3. Yee A, De Ravin SS, Elliott E, Ziegler JB (2008). "Severe combined immunodeficiency: A national surveillance study". Pediatr Allergy Immunol 19(4):298–302. doi:10.1111/j.1399-3038.2007.00646.x. PMID 18221464
4. a b "News From Indian Country - A rare and once-baffling disease forces Navajo parents to cope". Retrieved 2008-03-01
5. a b Li L, Moshous D, Zhou Y et al. (2002). "A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans." J. Immunol. 168(12):6323–9. PMID 12055248
6. Haq IJ, Steinberg LJ, Hoenig M et al. (2007). "GvHD-associated cytokine polymorphisms do not associate with Omenn syndrome rather than T-B-SCID in patients with defects in RAG genes." Clin. Immunol. 124(2):165–9. doi:10.1016/j.clim.2007.04.013. PMID 17572155
7. Pesu M, Candotti F, Husa M, Hofmann SR, Notarangelo LD, O"Shea JJ (2005). "Jak3, severe combined immunodeficiency, and a new class of immunosuppressive drugs." Immunol. Rev. 203: 127–42. doi :10.1111/j.0105-2896.2005.00220.x PMID 15661026
8. "Wisconsin First State in Nation to Screen All Newborns for Severe Combined Immune Deficiency (SCID) or "Bubble Boy Disease""
9. "NEWBORN SCREENING FOR PRIMARY IMMUNODEFICIENCY DISEASE"
10. "MDCH Adds Severe Combined Immunodeficiency (SCID) to Newborn Screening"
11. "Severe Combined Immunodeficiency (SCID): Immunodeficiency Disorders: Merck Manual Professional." Retrieved 2008-03-01
12. a b Chinen J, Buckley RH (2010). "Transplantation immunology: solid organ and bone marrow". J. Allergy Clin. Immunol. 125 (2 Suppl 2): ​​S324-35
13. Vickers, Peter S. (2009). Severe combined immune deficiency: early hospitalization and isolation. Hoboken NJ: John Wiley & Sons, 29-47. ISBN 978-0-470-74557-1
14. Buckley RH (2004). "Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution". Annu. Rev. Immunol. 22(1):625-655

Catad_tema Pathology of the immune system - articles

Severe combined immune deficiency in children

ICD 10: D81

Year of approval (revision frequency): 2016 (reviewed every 3 years)

ID: KR335

Professional associations:

• National Society of Pediatric Hematology and Oncology
• National Society of Experts on Primary Immunodeficiencies

Approved

National Society of Pediatric Hematologists and Oncologists

Agreed

Scientific Council of the Ministry of Health of the Russian Federation__ __________201_

Severe combined immune deficiency

Pneumocystis pneumonia

Maternal chimerism

Prenatal diagnosis

Hematopoietic stem cell transplantation

Intravenous immunoglobulin

List of abbreviations

ADA - adenosine deaminase

ADP - adenosine diphosphate

ALT - alanine aminotransferase

AR - autosomal recessive type of inheritance

AST - aspartate aminotransferase

ATG - antithymocyte globulin

ACD - anemia of chronic diseases

BCG - bacillus Calmette-Guerin

IVIG - intravenous immunoglobulins

GCS - glucocorticosteroids

G-CSF - granulocyte colony-stimulating factor

DNA - deoxyribonucleic acid

Gastrointestinal tract - gastrointestinal tract

IG - immunoglobulin

CIN - combined immune deficiency

BM - bone marrow

CT - computed tomography

Health care facility - medical and preventive institution

MOH - Ministry of Health

ICD-10 - International classification diseases 10th revision

MRI - magnetic resonance imaging

PNP - purine nucleoside phosphorylase

PCR - polymerase chain reaction

RCT - randomized controlled trials

RNA - ribonucleic acid

GVHD - graft versus host disease

RF - Russian Federation

DDS - DiGeorge syndrome

USA – United States of America

HSCT - hematopoietic stem cell transplantation

SCID - severe combined immune deficiency

Ultrasound - ultrasound examination

FSCC DGOI - Federal scientific and clinical center pediatric hematology, oncology and immunology

XС - X-linked type of inheritance

CVC - central venous catheter

CNS - central nervous system

ECG - electrocardiography

ADA - adenosine deaminase

CD - cluster of differentiation

CRP - C-reactive protein

eADA - erythrocyte adenosine deaminase

EBV - Epstein-Barre visrus - Epstein-Barr virus

GPPs - good practice points

HLA – human leukocyte antigens – human histocompatibility antigens

IL - interleukin

IUIS – International Union of Immunological Societies - International Union

immunological societies

NGS – next generation sequencing - next generation sequencing

PNP - purine-nucleoside phosphorylase - purine nucleoside phosphorylase

SIGN 50 - Scottish Intercollegiate Guidelines Network

TAP - transporter associated protein

WHN - winged helix nude С

ZAP - zeta associated protein

Terms and Definitions

Intravenous immunoglobulins – preparations containing predominantly normal human IgG. They are made from pooled plasma of thousands of healthy donors, using special purification and virus inactivation methods.

Polymerase chain reaction- a method of molecular biology that allows you to amplify (multiply) a specific section of DNA

Sequencing DNA - determination of its nucleotide sequence. As a result of sequencing, a description of the primary structure of linear DNA is obtained in the form of a nucleotide sequence in text form.

Hematopoietic stem cell transplantation – a method of treating some hereditary and acquired hematological, oncological and immune diseases, based on replacing the patient’s own pathological hematopoiesis with the normal hematopoiesis of the donor.

Autosomal recessive type of inheritance – inheritance of gene mutations, when for the disease to manifest, a mutation of a gene localized in the autosome must be inherited from both parents. The mutation appears only in the homozygous state, that is, when both copies of the gene located on homologous autosomes are damaged. If the mutation is in a heterozygous state, and the mutant allele is accompanied by a normal functional allele, then the autosomal recessive mutation does not manifest itself (carriage).

X-linked type of inheritance– inheritance of mutations of genes located on the X chromosome. In this case, females are usually asymptomatic carriers, and only males suffer from the disease.

TREC– circular DNA fragments formed during the development of T lymphocytes in the thymus, in particular, during the formation of the T cell receptor. Their concentration in the blood reflects the effectiveness of thymopoiesis. Used to screen for T cell immunodeficiencies.

1. Brief information

1.1 Definition

Severe combined immune deficiency (SCID) is a genetically determined (primary) immunodeficiency characterized by the almost complete absence of mature T-lymphocytes in the presence or absence of B- and NK-lymphocytes, which leads to early, extremely severe infections of viral, bacterial and opportunistic nature and, in the absence of pathogenetic therapy, death in the first two years of life.

1.2 Etiology and pathogenesis

SCID is caused by mutations in various genes responsible for the maturation and function primarily of T lymphocytes, and in some cases, other subpopulations of lymphocytes. Currently, the genetic nature of more than 15 forms of SCID is known (Table 3), some patients have still not verified genetic defects. The disease can be inherited either X-linked (in about a quarter of cases) or autosomal recessively. The estimated frequency of certain genetic defects, calculated based on data from perinatal screening for SCID in the United States, is presented in Fig. 1.

Figure 1. Frequency of detection of various defects in SCID.

As is known, T lymphocytes are the main effector and regulatory cells specific immunity. In their absence, the functions of antimicrobial and antiviral immunity suffer, and the formation of self-tolerance is disrupted. Even in cases where B lymphocytes are present in patients, the function of specific antibody formation also suffers significantly, since its implementation requires interaction between T and B lymphocytes.

1.3 Epidemiology

The birth rate of patients with SCID is 1:58,000 newborns (1:46,000-1:80,000); males predominate among patients.

1.4 Coding according to ICD-10

Combined immunodeficiencies(D81):

D81.0 - Severe combined immunodeficiency with reticular dysgenesis;

D81.1 - Severe combined immunodeficiency with low levels of T and B cells;

D81.2 - Severe combined immunodeficiency with low or normal B-cell counts;

D81.3 - Adenosine deaminase deficiency;

D81.4 - Nezeloff syndrome;

D81.5 - Purine nucleoside phosphorylase deficiency;

D81.6 - Deficiency of class I molecules of the major histocompatibility complex;

D81.7 - Deficiency of class II molecules of the major histocompatibility complex;

D81.8 - Other combined immunodeficiencies;

D81.9 - Combined immunodeficiency, unspecified.

1.5 Classification

According to the 2015 classification of PIDS, approved by the International Union of Immunological Societies (IUIS), there are 2 groups of SCID, depending on the presence or absence of B-lymphocytes: T-B- and T-B+. These two large groups can also be divided into subgroups depending on the presence or absence of NK cells: T-B-NK+, T-B-NK-, T-B+NK+, T-B+NK- (Table 1).

The clinical picture of the disease is practically independent of the genetic form of SCID.

Table 1. Type of inheritance and immunological disorders in the main forms of severe combined immune deficiency

2. Diagnostics

According to the European Society of Immunodeficiency (ESID) consensus, a combination of features is required to confirm the diagnosis of SCID:

• one of the following: invasive bacterial, viral, fungal or opportunistic infections; prolonged diarrhea with retarded physical development; family history of SCID;
• onset of symptoms at 1 year of life;
• exclusion of HIV infection;
• two of the following criteria: significantly reduced/absent CD3+ or CD4+ or CD8+ lymphocytes; reduced naïve CD4+ and/or CD8+ lymphocytes; increased g/d T lymphocytes; significantly reduced/absent proliferation in response to mitogens or TCR stimulation.

2.1 Complaints and anamnesis

The patient’s parents usually complain about loose stools that appeared in the first months of life, lack of weight gain, which are difficult to treat diaper dermatitis and thrush in the mouth. Sometimes parents report one or more severe infections (pneumonia, sepsis), but often the first respiratory infection is so severe that it suggests immunological deficiency.

When collecting a family history, one should pay attention to cases of repeated severe infections and deaths of children in early age with the clinic infectious diseases. The death of boys in several generations in the family suggests an X-linked nature of the disease. Consanguineous marriage among parents increases the likelihood of an autosomal recessive pathology.

When interviewing parents, it is necessary to clarify the characteristics of the child’s physical development, weight gain, timing of occurrence, frequency and severity of infectious diseases (diarrhea, fungal infections of the skin and mucous membranes, pneumonia and infections of other localizations). It is also necessary to find out whether BCG vaccination was carried out in the maternity hospital, whether changes were noted at the site of BCG vaccination and regional lymph nodes 3-4 months after vaccination.

2.2 Physical examination

Patients with SCID usually lose weight from the first months of life. Patients with SCID often experience “unmotivated” low-grade fevers and fever without an obvious source of infection at the time of presentation. However, the opposite situation often occurs - the absence of a temperature response to a severe, generalized infection.

It is important to pay attention to the presence of candidiasis of the skin and mucous membranes, the presence of maceration of the perianal area (due to chronic diarrhea). In the case of previous transfusion of non-irradiated red blood cells to patients or during the engraftment of maternal lymphocytes (maternal chimerism), a maculopapular polymorphic rash is possible, indicating the presence of graft-versus-host disease. Needs to be inspected left shoulder at the site of BCG vaccination to exclude local BCGitis and the rest of the skin for infiltrative polymorphic elements (generalized BCGitis).

In general, SCID patients are characterized by hypoplasia of peripheral lymphoid tissue, but in the case of BCGitis, left axillary lymphadenopathy may be observed.

Pneumonia in SCID often has an etiology of P.carinii. As is known, such pneumonia is accompanied by progressive respiratory failure with tachypnea, decreased oxygen saturation, and an abundance of crepitant wheezing.

Liver enlargement is often noted as a manifestation of toxic hepatitis due to defects in purine metabolism, liver form GVHD.

2.3 Laboratory diagnostics

Comments:Patients with SCID often have lymphopenia and may experience anemia of chronic inflammation.

It is recommended to determine biochemical blood parameters (urea, creatinine, bilirubin fractions, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase), as well as partial pressure of oxygen (pO2).

Comments:Determined to assess organ damage.

• A study of serum immunoglobulin levels is recommended.

Comments: In most cases, hypogammaglobulinemia is detected in patients with SCID from the first months of life. However, given the low age norms in children of the first year of life, assessment of the level of immunoglobulins is often uninformative in making a diagnosis of SCID. Don't forget also that high levels IgG in the first months of life is due to the persistence of maternal immunoglobulin obtained transplacentally and can occur in infants with SCID. Even with normal concentrations of immunoglobulins in SCID, their specificity suffers significantly, which can be determined by the low titer of post-vaccination antibodies in the case of vaccination of a child.

• Phenotyping of lymphocyte subpopulations is recommended.

Comments:During phenotyping, a significant decrease in T lymphocytes occurs in all forms of SCID, but the number of B lymphocytes and NK cells depends on the genetic defect underlying SCID.

Also, a normal or close to normal number of T lymphocytes is observed with maternal chimerism. These lymphocytes have a memory cell phenotype CD3+CD4+CD45RO+.

All variants of SCID are characterized by a significant decrease in the proliferative activity of lymphocytes.

• A TREC study (T cell excision circles) is recommended.

Comments:TREC are a measure of the efficiency of T lymphocyte production in the thymus. TREC concentrations are significantly reduced in all types of SCID, regardless of the genetic defect.

• Molecular genetic research of the relevant genes is recommended.

Comments:The clinical and laboratory picture is usually sufficient to confirm the diagnosis of SCID. Due to the need for immediate stem cell transplantation in SCID, genetic confirmation of the diagnosis is not required for its implementation, but is necessary for family counseling. Identification of causative gene mutations is carried out using polymerase chain reaction and subsequent sequencing of the resulting products or using next generation sequencing (NGS) methods, followed by confirmation of the defect using PCR. Usually they start with a study of the IL2RG gene in males, if its sequence is normal and/or female field patient - all other genes depending on the patient’s immunophenotype and the frequency of occurrence of the defect (the use of NGS panels is possible).

In cases of suspicious symptoms, it is necessary to exclude deletion of the short arm of chromosome 22 (DiGeorge syndrome) using the FISH method.

• Microbiological and virological studies are recommended.

Comments: Serological tests in patients with SCID are not informative and should not be used. The virological status of the patient is characterized by quantitative (preferably) or qualitative determination of viruses using the polymerase chain reaction (PCR) method in blood, feces, cerebrospinal fluid, broncho-alveolar lavage, and biopsy material. It must be remembered that the absence of viremia is not evidence of a negative virological status; it is necessary to study the appropriate media in case of damage to certain organs (up to a biopsy). Cultures of biomaterial (for flora and fungi) with determination of antibiotic sensitivity from mucous membranes, from foci of infection (including culture of blood and urine with appropriate symptoms), as well as cultures of feces, bronchoalveolar lavage, cerebrospinal fluid and biopsy material must always be carried out in the presence of infectious foci.

• HLA typing is recommended

Comments:Since prompt hematopoietic stem cell transplantation (HSCT) for SCID is the only condition for preserving the life of these patients, HLA typing with siblings, parents (in the absence of siblings), or typing to find an unrelated donor should be carried out immediately after the diagnosis of SCID.

2.4 Instrumental diagnostics

Computed tomography of the lungs is necessary to assess damage to this organ. The interstitial lung lesions characteristic of SCID cannot be fully assessed by chest radiography, so a CT scan of the lungs should be performed even if the radiograph is normal.

Ultrasound examination is recommended for all patients abdominal cavity and retroperitoneal space to assess the involvement of internal organs.

Other instrumental studies are carried out if there are appropriate clinical indications.

2.5 Other diagnostics

Due to frequent viral eye infections in patients with SCID, an examination by an ophthalmologist, including a slit lamp examination, is necessary. If the lungs are affected, broncho-alveolar lavage is performed, if the central nervous system is affected, a lumbar puncture is performed, followed by microbiological and virological examination of the media.

Differential diagnosis should primarily be made with:

? manifestations of HIV infection;

? other (syndromic) combined immunodeficiencies, primarily DiGeorge syndrome (which is characterized by a combination varying degrees severity of symptoms: structural features of the facial skeleton, morphology of the ears, decoupling of the hard and soft palate, hypocalcemia due to hypotrophy of the parathyroid glands, conotruncal malformations of the heart, other developmental defects, mental retardation);

? septic condition, in which transient deep lymphopenia is often noted;

? defects of the lymphatic vessels, primarily intestinal lymphangiectsia, in which lymphopenia, hypogammaglobulinemia and hypoalbuminemia are often ignored.

3. Treatment

3.1 Conservative treatment

Goal of treatment: stabilization of the condition and prevention of new infectious episodes during the period of preparation for HSCT.

• Immediately after the diagnosis of SCID, it is recommended that the child be kept in gnotobiological conditions (sterile box).

Comments:SCID is a pediatric emergency.

• Continuing breastfeeding is not recommended due to the risk of infection, primarily CMV, and also due to increased diarrhea when using lactose-containing products. Recommended artificial feeding, based on hydrolyzed mixtures, dairy-free cereals and other age-appropriate products that have undergone thorough heat treatment.

• In the absence of infectious foci, constant preventive antimicrobial therapy with a broad-spectrum drug is recommended, antifungal therapy with fluconazole (when receiving cultures - according to sensitivity), prevention of Pneumocystis infection with co-trimoxazole (preventive dose 5 mg/kg, therapeutic dose 20 mg/kg of co-trimoxazole intravenously) , prevention of CMV infection with ganciclovir.

Comments:Since in Russia BCG vaccination is carried out in the first days of life, children with SCID in most cases become infected, and they develop BCG-itis of varying severity (from local to generalized infection). BCG infection requires long-term treatment intensive care no less than 3 antimycobacterial drugs. In case of infection, intensive antimicrobial, antiviral and antifungal therapy by sensitivity.

• If there are symptoms of GVHD and/or immune damage to organs, immunosuppressive therapy with glucocorticosteroids and other immunosuppressive drugs is recommended - individually.

• If transfusions of blood components (erythrocyte mass, platelet concentrate) are necessary, it is recommended to use only irradiated and filtered drugs. In case of transfusion of non-irradiated erythrocytes and platelets, post-transfusion GVHD develops.

• Due to massive immune damage to organs, immunosuppressive therapy in the form of glucocorticosteroids (GCS) 1-1.5 g/kg body weight is recommended until HSCT. In case of incomplete effect and/or development of significant side effects from GCS therapy, therapy with anti-thymocyte immunogloblin at a dose of 10 mg/kg for 3 days is recommended.

• Recommended preventive treatment using intravenous immunoglobulin transfusion (IVIG) from the moment of diagnosis until the restoration of immune function after HSCT, since all patients with OM, regardless of the level of serum immunoglobulins, have impaired antibody production.

Comments: In patients with OM, treatment is carried out weekly at a dose of 400–600 mg/kg. For the treatment of severe infections, IVIG is used at a dose of 1 g/kg, for the treatment of septic conditions - IVIG enriched with IgM (normal human immunoglobulin) at a dose of 3 ml/kg per day for 2-5 injections.

3.2 Hematopoietic stem cell transplantation

The goal of treatment is to save the patient's life.

• HSCT is recommended for all SCID patients

Comments: If SCID is diagnosed during the first month of life, before the onset of infectious complications, adequate therapy and allogeneic HLA identical or haploidentical stem cell transplantation (HSCT) ensures survival in more than 90% of patients, regardless of the form of immunodeficiency. In case of later diagnosis, severe infections develop that are difficult to treat, and patient survival rate drops sharply - to 40-50%. In any case, HSCT is the only curative treatment method for patients with SCID; without HSCT, mortality is 100% in the first 12-18 months of life.

It is carried out from a related compatible, unrelated compatible or haploidentical donor according to the methods used in a specific center. Depending on the infection status and developed complications, the presence and intensity of conditioning is determined. In the absence of a compatible related donor, the results of haplotransplantation are comparable to the results of an unrelated transplantation from a fully compatible donor, but haplotransplantation is possible in as soon as possible Therefore, if the patient's condition is unstable, transplantation from the parents is preferable.

3.3 Surgical treatment

It is carried out according to indications, depending on complications.

3.4 Gene therapy

Currently active clinical researches, which will make it possible to routinely use gene therapy for some forms of SCID.

4. Rehabilitation

From the moment of diagnosis until the start of restoration of immune function after HSCT, the patient should be in a hospital specializing in the management of patients with SCID.

5. Prevention and clinical observation

Preventive measures include medical genetic counseling of families and prenatal diagnosis, which is carried out using a molecular genetic study of chorionic villus sampling to identify mutations in the corresponding gene, which helps prevent the birth of other patients with this disease in SCID families.

Required prenatal diagnosis for all subsequent pregnancies of the mother in this marriage and in other marriages with an X-linked type of inheritance. With an X-linked type of inheritance, testing for carriage of the mutation is necessary for the patient’s sisters and all the mother’s sisters childbearing age, according to testimony - other female relatives.

Prenatal diagnosis is indicated only in consanguineous marriages. In other cases, the risk of the disease in the patient's children is less than 0.1%. All children of a patient with an autosomal recessive type of inheritance and all daughters of a patient with an X-linked type of inheritance are carriers of the mutated gene; they need family counseling.

6. Additional information affecting the course and outcome of the disease

With successful HSCT, the prognosis for quality and life expectancy is generally favorable; it is largely determined by the severity of chronic foci of infection and organ damage that have formed at the time of transplantation. Average duration The life expectancy of SCID patients without HSCT is currently 7 months.

Criteria for assessing the quality of medical care

Bibliography

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Appendix A1. Composition of the working group

Balashov Dmitry Nikolaevich- Doctor of Medical Sciences, member of the National Society of Experts in the Field of Primary Immunodeficiencies, member of the National Society of Pediatric Hematologists and Oncologists, member of the European Society of Immunodeficiencies

Rumyantsev Alexander Grigorievich - Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Medical Sciences, President of the National Society of Experts in the Field of Primary Immunodeficiencies, Member of the National Society of Pediatric Hematologists and Oncologists, Member of the European Society of Hematologists

Shcherbina Anna Yurievna- Doctor of Medical Sciences, Executive Director of the National Society of Experts in the Field of Primary Immunodeficiencies, member of the National Society of Pediatric Hematologists and Oncologists, member of the European Society of Immunodeficiencies

Conflict of interest: Sherbina A.Yu. over the past 5 years, she has been lecturing with the support of the companies CSL Behring, Kedrion, Biotest, RFarm, which are manufacturers\distributors of intravenous immunoglobulin preparations.

Hematologists 01/14/21;

Immunologists 03/14/09;

Pediatricians 01/14/08;

General practitioners 08/31/54.

Table P1– Levels of evidence

Table P2– Recommendation strength levels

Appendix B: Patient Information

Severe combined immune deficiency (SCID) is a genetically determined disease, which is based on a severe defect of the immune system. The disease is characterized by severe viral and bacterial infections and, in the absence of stem cell transplantation, death in the first two years of life.

SCID is caused by defects (mutations) in various genes responsible for the maturation and function primarily of T lymphocytes, and in some cases, other subpopulations of lymphocytes. Currently, the genetic nature of more than 15 forms of SCID is known; some patients have genetic defects that have not yet been verified. Patients with SCID are characterized by an early (in the first weeks or months of life) onset of clinical manifestations of the disease in the form of loose stools, persistent thrush, diaper dermatitis, and severe infections. If a child is vaccinated with BCG in the maternity hospital or later, the development of regional and/or generalized BCG infection is typical.

Against the background of severe infections, there is a lag in physical and motor development. It should be remembered that even with SCID, infants do not immediately develop all of the above symptoms and may grow and develop normally within a few months. Transplacental transfer of maternal lymphocytes can cause symptoms of graft-versus-host disease (GVHD), referred to as maternal-fetal GVHD. It manifests itself mainly in the form of a skin rash and/or damage to the liver and intestines.

HSCT is the only way to save the patient's life. HSCT is performed from a compatible brother/sister, or, in their absence, from an unrelated compatible donor or from parents. The outcomes of HSCT depend largely on the existing infectious status, damage to organs and systems.

The risk of having other children with SCID in this family is approximately 25%. It is recommended to conduct family counseling and prenatal/preimplantation diagnostics to exclude the birth of other children with this disease.

Phenotype: No acquired immunity; rudimentary thymus; few thymocytes and Hassell bodies.

Clinical manifestations: Skin infections, sepsis, pneumonia and diarrhea starting at 3 months of age; growth retardation; severe opportunistic infections (eg, Pneumocystis, Candida); hypoplasia of lymphoid tissue; chondrodysplasia; death is likely by age 2 years (without treatment).

immunodeficiency disease

Partial combined immunodeficiencies

Wiskott-Aldrich syndrome

Phenotype: Accelerated synthesis and catabolism of all Igs; congenital platelet defect.

Clinical manifestations: Eczema; thrombocytopenia; recurrent infections; Pneumocystis and herpetic infection in adolescence; malignant tumors in 10-12% of cases.

Ataxia-telangiectasia (Liu-Bar syndrome).

Phenotype: Thymic hypoplasia; few Hassell bodies; congenital defects of T- and B-lymphocytes.

Clinical manifestations: Progressive cerebellar ataxia; telangiectasia; recurrent infections; malignant neoplasms are common.

Defects of the mononuclear phagocyte and granulocyte system.

The presentation of antigenic substances to lymphocytes can be disrupted by insufficient activity of auxiliary A-cells - macrophages and biologically active substances, where complement is of primary importance.

A deficiency of the mononuclear phagocytic system is determined by a disorder in the ability of auxiliary cells to lyse bacteria, process and present antigens to T- and B-lymphocytes. One form of phagocyte system deficiency is described as Chediak-Higashi syndrome. It is manifested by defects in the structure of lysosomes, delayed formation of phagolysosomes, and ineffective lysis of bacteria. In sick people, the development of chronic bacterial infections, albinism due to defects in the pigment cells of the retina and skin, and photophobia are observed. In the early postnatal period, mortality is high.

Complement system defects

Genetic defects in almost all 9 components of the complement system and 5 inhibitors have been described. The most common hereditary complement defect is C1 inhibitor deficiency, inherited in an autosomal dominant manner. This deficiency is associated with the development of angioedema, or Quincke's disease.

Insufficiency of individual components of the complement system leads to loss or weakening of its main biological effects:

regulation and induction of the immune response;

stimulation of neutrophil chemotaxis;

immune adhesion - the initial phagocytosis;

immune cytolysis;

opsonization of bacteria;

conglutination reactions;

activation of the kinin coagulation system;

Diagnosis of primary immunodeficiencies

Since immunodeficiencies are often inherited, it is important to identify a family history of other children with similar diseases, and also to determine whether the parents are related to each other, since many of these diseases are transmitted as recessive trait. The specific diagnosis of immunodeficiency is determined by its nature, i.e., which part of the immune system is impaired: the system of T-, B-lymphocytes, macrophages, other cells of the immune system, or the biosynthesis of antibodies.

For this purpose, the following studies are carried out:

• 1. Full analysis blood with counting the total number of lymphocytes. If there are less than 2000 in 1 ml, then we can assume the presence of immunodeficiency. It is also important to install total separately B- and T-lymphocytes and high-quality composition the latter. Platelet counts can detect thrombocytopenia, which is often seen in these diseases.
• 2. Determination of the total level of immunoglobulins and their quantitative and qualitative ratio in blood serum. The content of immunoglobulins less than 400 mg% or IgG less than 200 mg% in 100 ml of blood gives reason to suspect immunodeficiency.
• 3. X-ray examination of the nasopharynx and neck in a lateral projection. The absence of a shadow of the thymus and lymphoid tissue indicates cellular immunodeficiency.
• 4. Test for delayed type hypersensitivity. Its absence is evidence of a defect in the number or functions of T-lymphocytes.
• 5. Determination of the mitogenic effect of phytohemagglutinin on lymphocytes or determination of the effect of blast transformation. Their absence or weak manifestation also indicates a deficiency of T cells.
• 6. Determination of phagocytic activity and activity of the complement system in experiments with live bacteria. In patients suffering from primary immunodeficiency, the functions of these systems are often suppressed, so they are susceptible to various infectious processes.
• 7. Use of other, more specialized tests used to study immune status.

Treatment of primary immunodeficiency

Depending on the severity of immunodeficiency and its type, treatment may have its own characteristics.

Important points are assessing the feasibility of using live vaccines, stopping smoking and drinking alcohol, prescribing broad-spectrum antibiotics for bacterial infections or modern antiviral drugs for diseases caused by viruses.

Immunocorrection is possible:

using bone marrow transplantation ( important body immune system);

replenishment of individual elements of the immune system, for example, immunoglobulins;

Secondary (acquired). They are a consequence of impaired immunoregulation, which is associated with injuries, infections, therapeutic effects and other reasons.

Secondary immunodeficiencies are acquired diseases of the immune system, as well as primary immunodeficiencies associated with weakened immunity and an increased incidence of infectious diseases. Perhaps the best known secondary immunodeficiency is AIDS resulting from HIV infection.

Secondary immunodeficiencies may be associated with infections (HIV, severe purulent infections...), medicines(prednisolone, cytostatics), radiation, some chronic diseases(diabetes).

That is, any action aimed at weakening our immune system can lead to secondary immunodeficiency. However, the rate of development of immunodeficiency and its inevitability can vary greatly, for example, with HIV infection, the development of immunodeficiency is inevitable, while not all people suffering from diabetes mellitus, may have an immunodeficiency state even years after the onset of the disease.

Secondary immunodeficiencies associated with HIV.

AIDS - it is known that its causative agent HIV is capable of selectively infecting and disabling only one of the list of subpopulations of T-lymphocytes, namely T-helpers. But even with such a selective defect, changes are noted both in the body’s humoral defense mechanisms and in the cellular ones, since T-helpers belong to the immunoregulatory subpopulations of T-lymphocytes. Typically, patients die from severe infections caused by various pathogenic and opportunistic microorganisms.

Secondary immunodeficiencies associated with antibiotic therapy.

It must be remembered that immune disorders may occur after any, even rational, antibiotic therapy. This group of patients is characterized by a high risk of developing infections caused by both pathogenic or opportunistic microorganisms that live in environment or part of the resident microflora.

Secondary immunodeficiencies associated with burns and tumors.

Burns of the skin lead to the free penetration of microorganisms into the body, and also disrupt the water and electrolyte balance. Second- and third-degree burns significantly reduce the severity of cellular reactions. With burns covering more than 20% of the body surface, a decrease in the ability of phagocytes for chemotaxis often develops. Patients with severe burns and sepsis are characterized by an increase in the number of T-suppressor cells in the peripheral blood. Disturbances in spleen function or splenectomy lead to a decrease in IgM synthesis.

A significant portion of IgM is formed in the lymphoid tissue of the spleen; The main function of AT of this class is opsonization of microorganisms that have a capsule. Patients are at increased risk of developing pneumonia, bacteremia, and meningitis. Hematopoietic disorders are accompanied by a rapid decrease in the number of circulating segmented neutrophils, which have a short life span. Leukopenia can progress until there is a complete absence of segmented neutrophils in the blood (agranulocytosis). Patients are susceptible to a variety of infections—pneumonia, bacteremia, and urinary tract infections are the most common. Malignant neoplasms of any type are accompanied by disturbances in the patient’s immune status. Suppression of cellular immune responses is observed in patients with solid epithelial tumors and chronic lymphoproliferative diseases. This principle of systematization of immunodeficiency states is based on an analysis of the immediate causes of their occurrence. Genetically determined immunodeficiency states are detected mainly in children in the first months of their life, and such children do not survive, most often up to one year, unless active treatment is carried out, in particular, replacement of detected defects.

Diagnosis of secondary immunodeficiencies.

A prerequisite for identifying immunodeficiency is a chronic (often recurrent) infection.

In most cases, the simplest tests can reveal serious damage to the immune system: the total (absolute) number of leukocytes, as well as their subtypes of neutrophils, lymphocytes and monocytes, the level of serum immunoglobulins IgG, IgA, IgM, testing for human immunodeficiency virus (HIV).

Much less often there is a need to diagnose more subtle elements of the immune system: phagocytic activity of macrophages, subtypes of B and T lymphocytes (determination of so-called CD markers) and their ability to divide, production of inflammatory factors (cytokines), determination of elements of the complement system, etc. .

Treatment of secondary immunodeficiency

The treatment of secondary immunodeficiency is based on the following general principles:

infection control;

vaccination (if indicated);

replacement therapy, for example, with immunoglobulins;

use of immunomodulators.

Prevention of immunodeficiencies

Due to the hereditary nature of primary immunodeficiencies, there is no prevention for this group of diseases.

Prevention of secondary immunodeficiencies mainly comes down to avoiding HIV infection (protected sex, use of sterile medical instruments, etc.).