Immunodeficiencies are independent diseases (nosological forms) and concomitant syndromes characterized by insufficiency of the immune system. Frequency
- 1 in 500 babies are born with a compromised immune system
- A much larger number of individuals acquire transient or permanent immunodeficiency during their lifetime. Risk factors
- A burdened family history
- Almost all bad habits
- Primary – congenital (genetic) damage to the immune system (see.
- Primary immunodeficiency, WHO classification
- , Appendix 5.)
- Secondary – deficiency develops due to endogenous and exogenous effects on the normal immune system (for example, within 90% of all viral infections is accompanied by transient immunosuppression)
- Selective – caused by selective damage to various populations of immunocompetent cells
- Non-specific – defect(s) of non-specific resistance mechanisms (non-specific immunity), phagocytes and complement
- Combined – combined damage to cellular and humoral mechanisms (for example, B- and T-lymphocytes).
- Primary immunodeficiencies (manifested by the development of infectious lesions soon after birth, but may not have clinical manifestations until later age) – gene and chromosomal damage (numerous immunodeficiencies of various types)
- Secondary immunodeficiencies
- Immunosuppressive products (including phenytoin [difenin], penicillamine, glucocorticoids)
- Malnutrition or intestinal absorption
- Drugs and exposure to toxic substances
- Radiation therapy, chemotherapy
- Malignant tumors
- Viral infections (for example, HIV)
- Conditions that cause protein loss (eg, nephrotic syndrome)
- Asplenia. separate forms. There are many individual entities of immunodeficiency with extremely confusing terminology (see also Appendix 2. Hereditary diseases: mapped phenotypes).
- Severe combined immunodeficiency. In the classical version, both humoral (no AT) and cellular immunity (no T-cells and natural killers – NK-cells) are absent; alymphoplasia or lymphopenia (applies to both B-lymphocytes and T-lymphocytes). Unconditional susceptibility to bacterial, fungal, protozoal, viral infections; the introduction of live vaccines should be excluded; death begins by the end of the first year of life (unless a bone marrow transplant is performed). Approximately 70% of patients have B-lymphocytes (including with mutations in the IL genes, adenosine deaminase deficiency, naked lymphocyte syndrome). Types:
- Adenosine deaminase deficiency (EC 22.214.171.124, 3 isoforms, defective variants –
- 102700, 20ql2-ql3.ll, ADA gene defect, at least 30 alleles are known, R) is the cause of 50% of cases of severe combined immunodeficiency, the enzyme deficiency itself (recessive inheritance) is milder forms. Clinically: B- and T-cell immunodeficiency, CO4+-lymphopenia, thrombocytopenic purpura, hepatosplenomegaly, recurring bacterial, viral, fungal infections (mainly bronchopulmonary), all kinds of bone skeletal dysplasia are frequent.
- Swiss-type agammaglobulinemia (see Agammaglobulinemia).
- Purine nucleoside phosphorylase deficiency (see Enzyme Deficiency).
- Deficiency of transcobalamin II (*275350, 22ql2-ql3, damage to the TCN2, TC2, p genes), vitamin B12 transport protein. Clinically: severe megaloblastic anemia, agranulocytosis, thrombocytopenia, hemorrhagic diathesis, severe diarrhea, ulcerative stomatitis, repeated infections, agammaglobulinemia.
- Naked lymphocyte syndrome (#209920, 600005, 600006, 601863, 601861, including damage to the MHC2TA, RFX5, RFXAP, C2TA genes, all p). The term is used in relation to severe combined immunodeficiency with a lack of expression of a number of genes of the major histocompatibility complex class II (absence of HLA Ag on the plane of lymphoid cells). Clinically: persistent diarrhea, malabsorption syndrome, candidiasis, bacterial infections, interstitial pneumonia. Laboratory: panhypogammaglobulinemia, no antigen-stimulated lymphocyte proliferation and cell-mediated cytotoxicity.
- Atypical form (269840, p). Absent: CD8
- T-lymphocytes, their response to mitogens, AT to the T-cell receptor. The content of Ig is normal or increased, lymphadenopathy.
- X-linked form (#312863, mutations in the y-chain of the interleukin-2 receptor, N recessive). Weak development of lymphoid tissue, multiple genesis of infection; normal content of Ig, B- and NK-cells, reduced number of CD4+ and CD8
- T-lymphocytes, their weak proliferative response to antigen and mitogens.
- B- and T-cell-negative forms (#600802, 600173, 176947, including deficiency of Janus kinase-3, tyrosine kinase ZAP-70, p).
- B-cell-negative form (#601457, damage to the L4C gene).
- Variable general immunodeficiency (*240500) — immunodeficiency of multifactorial etiology; observed at any age in both sexes; the total number of Ig is traditionally less than 300 mg%, the number of B-lymphocytes is often within the normal range, there are no plasma cells; cellular immunity (T-lymphocytic), as a rule, is not changed; accompanied by frequent purulent infections, sometimes autoimmune diseases develop. Options:
- With severe diarrhea (125890, R): malabsorption of fats, vitamin B12, xylose
- Family form ®: with a lack of IgG and IgA, the content of IgM is increased
- With centromeric instability (*242860, chromosomes 1, 2, 9, 16; p): T- and NK-cell deficiency, reduced IgA content, facial dysmorphism, persistent infections, mental retardation
- X-linked hypogammaglobulinemia with GH deficiency (*307200), reduced number of B-lymphocytes, short stature, delayed onset of puberty, high susceptibility to infections.
- Nezelof’s syndrome (*242700, p, probable). A group of sporadic diseases, usually of unknown etiology, associated with repeated bacterial, fungal, protozoal, and viral infections; observe hypoplasia of the thymus gland, inhibition of cellular
(T-lymphocytic) and humoral (B-lymphocytic) immunity, although the content of Ig may be within the normal range. Synonyms: thymic alymphoplasia of the non-zelophic type, cellular immunodeficiency with impaired Ig synthesis, thymus aplasia.
- DiGeorge Syndrome
- Hyperimmunoglobulinemia syndrome M (*308230, Xq26, CD40 ligand defect, R, p). Neutropenia, hemolytic anemia, thrombocytopenia, frequent infections, deficiency of IgA, IgG, absence of IgE, increased content of IgM; the structure of lymphoid follicles is disturbed.
- Hyperimmunoglobulinemia syndrome E (147060,R; variants). Clinically: bacterial infections, candidiasis, osteoporosis, defective neutrophil chemotaxis, increased IgE content.
- Job syndrome (243700, p). High IgE, low IgA, skin hypersusceptibility to Ag Staphylococcus aureus and Candida albicans, eosinophilia, damage to leukocyte chemotaxis, persistent staphylococcal skin infections (cold abscesses, dermatitis), candidiasis of the skin and mucous membranes, other infections.
- Selective deficiency of IgA (137100, including with deletion 18q-, various types of inheritance). Secretory IgA is required for local protection at the mucosal plane. Clinically: frequent infections, autoimmune, atonic disorders, malabsorption.
- Lack of adhesion of leukocytes (#116920, 21q22.3, p2 mutations in the integrin gene chain [Ar CD18/CD11, 600065, within 10 defective alleles], p): bacterial infections, poor wound healing, damage to neutrophil phagocytosis and chemotaxis, treatment – transplantation bone marrow. Associated disease is juvenile rheumatoid arthritis.
- Other immunodeficiencies: Wiskott-Aldrich syndrome, ataxia-telangiectasia, chronic candidiasis of the skin and mucous membranes, chronic granulomatous diseases, albinism, AIDS, agammaglobulinemia.
Tactics of conducting
- Treatment is determined by the type of immunodeficiency
- Bone marrow transplantation is indicated for severe T-cell pathology
- In IgG deficiency, intravenous Ig injections
- Live vaccines should not be administered to immunocompromised patients and their families. With cellular immunodeficiency, transfusion of fresh blood and blood products is contraindicated. Before transfusion, blood and blood products will need to be irradiated (1500-3000 rad). Immunoglobulin and plasma should not be administered to patients with selective IgA deficiency. In thrombocytopenia, intramuscular injections (eg, immunoglobulins) should be avoided. Prescription of antibiotics is mandatory before surgical or dental interventions. Drugs of choice
- Almost all forms
- Antibiotics for the prevention and immediate treatment of infections
- Immunostimulants (eg, levamisole, ascorbic acid) to improve neutrophil function.
- In humoral and combined immunodeficiencies, Ig replacement therapy
- IV Ig (traditionally 200 mg/kg, then monthly at 100 mg/kg) raises serum IgG to 200 mg%
- If necessary, enter 400-800 mg/kg/month, maintaining the concentration of IgG in serum above 500 mg%
- With simultaneous insufficiency of IgA and IgG, the use is limited due to the risk of an anaphylactic reaction to exogenous IgA.
- In case of adenosine deaminase deficiency, replacement therapy with an enzyme conjugated with polyethylene glycol (Adagen) or gene therapy (corrected T-lymphocytes of the patient).
- For HIV infection, see HIV infection and AIDS. case management
- Condition control
- Careful monitoring of children with severe combined immunodeficiency is necessary, tk. exposure to any pathogenic factors can lead to death
- In patients with hypogammaglobulinemia, IgG levels should be monitored and maintained.
- Autoimmune diseases
- Development of serum sickness during treatment with y-globulin
- The development of malignant neoplasms (for example, with hypogammaglobulinemia, thymoma may develop)
- Severe infections
- Graft-versus-host disease, traditionally as a result of blood transfusion in patients with severe combined immunodeficiency. The course and prognosis significantly depend on the type and rate of progression of immunodeficiency.
Prevention. With primary immunodeficiencies, medical genetic counseling will be needed. Pregnancy. There is a transplacental transmission of HIV and the development of AIDS in the fetus. See also Agammaglobulinemia, Agranulocytosis, Autoimmune Polyglandular Syndrome, DiGeorge Syndrome, HIV infection and AIDS
- D80 Immunodeficiencies with predominant antibody deficiency
- D81 Combined immunodeficiencies
- D82 Immunodeficiencies associated with other significant defects
- D83 Common variable immunodeficiency
- D84 Other immunodeficiencies
Literature. Monafo WJ et al: A hereditary immunodeficiency characterized by CD8+ T-Iymphocyte deficiency and impaired lymphocyte activation. Clin. Exp. Immun. 90 390-393, 1992; Elder ME: Severe combined immunodeficiency due to a defect in the tyrosine kinase ZAP-70. Pediat. Res. 39: 743-748, 1996; Schwarz K et al. RAG mutations in human B cell-negative SCID. Science 274: 97-99, 1996; Nezelof C et al: L’hypoplasie hereditaire du thymus: sa place et sa responsabilite dans une observation d’aplasie lymphocytaire, normoplasmocytaire et normoglobulinemique du nourrisson. Arch. Franc. Pediat. 21: 897-920, 1964; Shuster DE et al: Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle. PNAS 89: 9225-9229, 1992
- The WHO classification of primary immunodeficiencies (Fudenberg HH et al: Classification of the primary immunodeficiency (WHO recommendation]. New Eng. J. Med. 283: 656-657, 1970) is now significantly outdated
- Job is a biblical character, in the book of Job (2:7) it is said
- Satan…hit Job with ulcers from the feet to the top of his head
- CD40 is a glycoprotein, expressed by B-lymphocytes, epithelial cells; a correlation was established between CD40 ligand expression and IgE production.