Primary immunodeficiencies

According to the latest classification of the International Union of Immunological Communities (IUIS) by the congenital immunity errors committee, all PIDs are divided into 9 classes ^[2] :

1. Combined immunodeficiencies
2. Combined PID associated with syndromic manifestations
3. Mostly antibody defects
4. PID with immune dysregulation
5. Congenital defects in the number and function of phagocytes
6. Defects of innate immunity
7. Autoinflammatory syndromes
8. Complement defects
9. Phenocopies

The primary diseases of cellular immunity include the following diseases:

1. Dee Georgie's Syndrome
2. Duncan's Syndrome
3. Purinucleoside phosphorylase deficiency
4. Orotaciduria
5. Biotin-dependent fermentopathies.

Dee Georgie Syndrome

The basis of Di George syndrome ( Di George ) is hypoplasia of the thymus. The syndrome was described in 1965. It is believed that this disease is not hereditary, it occurs as a result of an acquired violation of organogenesis in the III – V branchial arches (pharyngeal pockets) at 6–8 weeks of gestation. Therefore, in addition to the thymus defect, defects of the parathyroid glands, heart and large vessels, as well as orofacial defects (microstomy, micrognathia, hypertelorism, a low location of the auricles) are noted.

The result of hypoplasia of the parathyroid glands is a deficiency of parathyroid hormone and persistent hypocalcemia, as a result of which a convulsive syndrome develops, which can occur even in the first hours of life (neonatal tetany). The cause of death in older children is the complications associated with heart defects.

Disorders affecting T-lymphocytes can be either very deep or barely noticeable. In any case, the function of T cells with age is restored and by 5 years, if the child remains alive, it is not possible to detect their insufficiency. The antigen-independent stage of T-cell maturation in this case occurs outside the thymus - in stratified squamous epithelium, primarily in the epidermis. One effective way to treat Dee Georges syndrome is to transplant embryonic thymus tissue.

Duncan Syndrome

Duncan syndrome (X-linked lymphoproliferative syndrome) - immunodeficiency, characterized by increased sensitivity to the Epstein-Barr virus . The gene for hypersensitivity to the virus is localized on the X chromosome, the type of inheritance of the disease is recessive, so boys get sick. Patients who have undergone infectious mononucleosis develop a prolonged febrile state, lymphadenopathy (enlarged lymph nodes), peripheral blood lymphocytosis, hepato- and splenomegaly. Later, B-cell lymphoma forms, more often in the terminal sections of the small intestine, from which patients die. Lethal outcomes are also caused by destructive hepatitis caused by the Epstein-Barr virus.

Purine nucleoside phosphorylase deficiency

Purine nucleoside phosphorylase (PNP) deficiency is inherited in an autosomal recessive manner. Children suffer from hypoplastic anemia and extremely reduced T-cell function.

Orotaciduria

Orotaciduria is a hereditary disease of the synthesis of pyrimidines, which is manifested by increased excretion of orotic acid ( orotate ) with urine, T-lymphocyte deficiency, megaloblastic anemia, and mental and physical development retardation. In this disease, the activity of the orotidyl pyrophosphorylase and orotidyl decarboxylase enzymes, which convert orotic acid to nucleotide-orotidine monophosphate , necessary for the synthesis of nucleic acids, is reduced .

Biotin-dependent fermentopathy

Biotin-dependent fermentopathies are also accompanied by the development of cellular immunodeficiency (hereditary defects of biotinidase and biotin-dependent enzymes of pyruvate carboxylase and propionate carboxylase involved in the metabolism of branched chain amino acids - valine, leucine, isoleucine). The disease manifests itself already in the neonatal period with episodes of ketoacidosis, neurological symptoms, alopecia, skin rashes and protein intolerance (vomiting, maldigestion, dehydration). Urine contains a large amount of organic acids. Children lag behind in physical development. Of the infectious processes, candidiasis and keratoconjunctivitis most often develop. Biotin gives a good therapeutic effect.

The primary deficiencies of humoral immunity include the following main syndromes:

1. Bruton's syndrome ( Bruton type agammaglobulinemia )
2. West syndrome ( IgA deficiency )
3. IgG deficiency
4. Transcobalamin II deficiency
5. Hyper IgM Syndrome
6. Hyper-IgE syndrome ( Job syndrome, Staphylococcus aureus syndrome with hyper-IgE )
7. Hyper-IgD Syndrome ( Van der Meer Syndrome )
8. Late immune start .

Hereditary deficits of humoral immunity, with the exception of Bruton's syndrome and late immune start, are combined by the general term dysammaglobulinemia . In some forms of dysammaglobulinemia, a normal or even elevated level of immunoglobulins in the blood and mucous membrane secrets is determined.

Bruton Syndrome

Bruton's syndrome ( Bruton type agammaglobulinemia ) - immunoglobulin deficiency of all classes. The disease was the first studied immunodeficiency of hereditary nature (OG Bruton, 1952 ). Type of inheritance - recessive, linked to the X chromosome. In the first years of life, infectious complications develop, mainly bacterial. At the same time, viral infections occur in patients, as a rule, easily. The first signs of immunodeficiency become noticeable in the second year of life, although recurrent infections can occur in both an 8-month-old infant and a 3-year-old child. About a third of patients develop sluggish arthritis, similar to rheumatoid arthritis, with a sterile effusion in the cavity of one of the large joints.

In the event that substitution therapy (administration of immunoglobulin preparations) is started before repeated infections cause serious morphological changes (for example, bronchiectasis, chronic pneumonia and respiratory failure), the immediate prognosis is very good. However, in adolescence and youth, a gradually progressing neurological disease often develops, resembling a slow viral infection and manifesting as a dermatomyositis syndrome with severe edema and perivascular lymphohistioplasmacytic infiltrates. This severe systemic disease is fatal. It is believed that it is caused by enterovirus infection (enteroviruses were repeatedly isolated from the blood and cerebrospinal fluid of patients and deceased). In general, it should be noted the high sensitivity of these patients to enteroviruses. So, children with Bruton's syndrome are more likely to suffer from polio , and it is more difficult for them.

Selective Immunoglobulin Deficiency

Selective immunoglobulin deficiency is manifested by a persistent deficiency of immunoglobulins of one or more classes (primarily IgA and IgG).

West syndrome - a deficiency of class A immunoglobulins. The disease is manifested by frequent infectious lesions of the conjunctiva, respiratory and gastrointestinal tracts.

Secretory phase deficiency is a primary intestinal IgA deficiency.

Cases of hereditary insufficiency of the synthesis of kappa chains of immunoglobulins have been identified.

Selective Immunoglobulin M Deficiency

Main article Immunoglobulin M deficiency

Transcobalamin II deficiency

Transcobalamin II deficiency is manifested by B12-achrestic anemia with characteristic signs of megaloblastic anemia in the form of atrophy of the mucous membranes and funicular myelosis (atrophic processes in the tissue of the spinal cord, accompanied by the development of paresis, paralysis and sensitivity disorders). In addition, terminal differentiation of B-lymphocytes suffers. They are not able to transform into plasma cells and synthesize immunoglobulins.

Hyper IgM Syndrome

Hyper-IgM syndrome is a hereditary disease in which there is a deficiency of IgA and IgG, but a high level of IgM. A similar dysfunction of humoral immunity was found in adults suffering from frequent respiratory infections with the development of bronchiectasis, as well as in children with congenital rubella. In some patients, γ- and α-plasmocytes are completely absent, and then only IgM is produced in the body.

Hyper IgE Syndrome

Hyper-IgE syndrome ( Job syndrome, Staphylococcus aureus syndrome with hyper-IgE ) was described in 1966. The eponymous term includes the name of the patient. Boys get sick more often (60-70% of cases). In the first months of life, various infectious processes occur, caused mainly by Staphylococcus aureus ( S. aureus ). Eosinophilia, sometimes significant, and neutrophilic granulocytosis with a shift of the formula to the left are detected in the blood. Despite the high levels of IgE and histamine, no manifestations of anaphylaxis and atopy are observed. Among IgE antibodies, antistaphylococcal idiotypes predominate. Often cold abscesses form in the subcutaneous tissue.

Hyper IgD Syndrome

Hyper-IgD syndrome with intermittent fever ( van der Meer syndrome ). The disease was described in 1984. It manifests itself in relapsing febrile states, leukocytosis of up to 10-20 thousand cells per μl, headaches, an increase in tonsils and a significant increase in the concentration of IgD in the blood.

Late Immune Start

Transient immunoglobulin deficiency in the first months of life. In a newborn and an infant in the first 3-4 months. life there is a low concentration of immunoglobulins in the blood, especially IgG. After birth, the IgG level, provided by passive penetration through the placenta from the mother, rapidly falls during the first month of life, stabilizes in the second, and then begins to grow. Since this feature is detected in almost every child, it is not considered pathological, but is regarded as a transient borderline state . If the active synthesis of immunoglobulins in the infant begins after 4-6 months. life, then this condition is already referred to as pathological and is designated as a late immune start .

Normally, antibody formation in the baby’s body begins after birth, but if after the 20th week. pregnancy, the fetus is infected with rubella virus, cytomegalovirus, treponema pallidum, toxoplasma or other microorganisms, then antibody formation begins in the prenatal period. Detection of elevated levels of immunoglobulins in a newborn, especially IgM, indicates a prenatal infection (the concentration of IgM in the blood of the umbilical cord or in a newborn 200 mg / l or more can be considered evidence of antenatal infection).

Primary combined immunodeficiency states are divided into three groups: (1) severe combined immunodeficiencies , (2) combined immunodeficiencies with a mild defect in the immune response, and (3) minor immunodeficiency states .

Severe Combined Immunodeficiencies

Severe combined immunodeficiencies are immunodeficiency conditions in which a child dies in the first months or in the first years of life (such children rarely live more than 1-2 years). The only treatment option for these diseases is bone marrow transplantation.

The following diseases belong to this group:

1. Reticular dysgenesis
2. Syndrome of “naked lymphocytes”
3. Wiskott-Aldrich Syndrome [severe]
4. Gitlin's syndrome
5. Glanzman's disease — Rinicker’s ( Swiss type agammaglobulinemia )
6. Good's syndrome ( immunodeficiency with thymoma )
7. Nezelof's syndrome ( French type agammaglobulinemia )
8. Omenn's Syndrome
9. Adenosine deaminase deficiency [severe forms].

Reticular Dysgenesis

Reticular dysgenesis is manifested by aplasia of the hematopoietic tissue. The differentiation block in this disease is localized already at the level of the hematopoietic stem cell. Children die antenatally or shortly after birth from infectious-septic complications or malignant neoplasms.

Naked Lymphocyte Syndrome

Syndrome of “naked” lymphocytes is a severe combined immunodeficiency in which body cells, including lymphocytes, do not express HLA-I molecules. In this case, a T-dependent immune response becomes impossible. The number of T and B lymphocytes in the blood is normal. The disease manifests at the age of 3-6 months. in the form of various infections. Growth retardation is characteristic.

Wiscott — Aldrich Disease

Wiskott — Aldrich Disease — Immunodeficiency with thrombocytopenia and eczema. Type of inheritance - recessive, linked to the X chromosome. Infectious processes in this disease develop, as a rule, at the end of the first year of life. The results obtained in the study of the pathogenesis of Wiskott-Aldrich syndrome confuse researchers. In the early stages of the disease, the organs of the immune system are not changed, however, as it progresses, lymphocytes begin to disappear from the thymus and lymph nodes of the lung roots (!). The most pronounced changes occur in the T-system of immunity. The humoral response suffers less - IgM production decreases.

Gitlin Syndrome

Gitlin's syndrome is a combination of severe combined immunodeficiency with insufficient production of growth hormone. Patients with dwarf growth. The disease is also accompanied by immaturity of the thymus. The arrest of its development in Gitlin's syndrome is also associated with growth hormone deficiency.

Glanzman's disease — Rinicker

Glanzman-Rinicker disease is a severe immunodeficiency, described in 1950 by Swiss doctors, whose names the disease is named. Death in the absence of active therapy occurs in most cases in the second half of the first year of life, when mother's milk begins to be displaced from the baby’s diet by other products. In the first months, the baby receives antibodies with breast milk, while it is protected by passive immunity. Thymus mass reduced by 5-10 times.

Hood Syndrome

Hood's syndrome ( immunodeficiency with thymoma ) is the primary immunodeficiency, which is characterized by immaturity of the thymus ( fetal thymus ), in which a tumor later develops from stromal epithelial cells ( thymoma ). Malignant variants of this tumor occasionally occur. Hypoplastic anemia is characteristic.

Nezelof's Syndrome

Nezelof's syndrome is a primary immunodeficiency caused by thymus hypo- or dysplasia. Moreover, as a result of its functional insufficiency, a differentiation of T-lymphocytes occurs.

Omenn's Syndrome

Omenn's syndrome is described in 1965 (GS Omenn) under the name of family reticuloendotheliosis with eosinophilia . It is manifested by severe immunodeficiency, skin lesions of the type of erythroderma and eczema, alopecia, chronic diarrhea, lymphadenopathy, hepatosplenomegaly, recurrent respiratory infections, leukocytosis (up to 25 thousand cells per μl) and blood eosinophilia. Thymus hypoplasia is characteristic. The prognosis is usually poor.

The pathogenesis of the syndrome is associated with the destruction of the tissues and organs of the child by maternal lymphocytes proliferating in his body. Typically, single maternal lymphocytes enter the blood of the fetus, but if there are a significant number of such cells and they make up a significant amount of lymphoid tissue, then the graft versus host reaction ( GVHD ) develops. В качестве трансплантата при этом синдроме выступают материнские лимфоциты. Особенно тяжёлые изменения развиваются в печени и в селезёнке, где под влиянием материнских лимфоцитов развиваются множественные мелкоочаговые некрозы . Синдром Оменна можно рассматривать как перинатальную форму РТПХ наряду со взрослой ( гомологичная болезнь ) и детской ( рант-болезнь ) формами.

Недостаточность аденозин-дезаминазы

Фермент аденозин-дезаминаза (АДА) у млекопитающих встречается во всех тканях, но наибольшая его концентрация выявляется в тимусе (в 10—15 раз больше, чем в других тканях). Поэтому дефицит или дефект этого энзима сопровождается прежде всего нарушениями в функционировании тимуса.

Комбинированные иммунодефициты с умеренновыраженным дефектом иммунитета

К комбинированным иммунодефицитам с умеренновыраженным дефектом иммунитета (при этих заболеваниях больные живут несколько десятилетий) относятся следующие синдромы:

1. Атаксия-телеангиэктазия Луи-Бар
2. Наследственная недостаточность цинка
3. Синдром Мак-Кьюсика ( метафизарная хондродисплазия , «гипоплазия хрящей и волос» ).

Атаксия-телеангиэктазия Луи-Бар

Atyxia-telangiectasia Louis-Bar is a hereditary disease in which, as a rule, severe immunodeficiency does not occur, so patients on average live up to 30-40 years. The most persistent symptom — a low level or lack of IgA — occurs in approximately 70% of patients. The disease is described in 1941 .

In addition to immunodeficiency, the following syndromes develop:

• Cerebellar hypoplasia (underdevelopment of cerebellum tissue) is manifested by impaired coordination of movements ( ataxia ); gait disturbance develops, as a rule, from the age of 4 and gradually progresses.
• Insufficiency of DNA repair enzymes in the cells of various organs, as a result of which the frequency of somatic mutations ( genome instability ) increases and malignant tumors often arise.
• Teleangiectasias are multiple foci of dilated small vessels of the conjunctiva and skin (detected by the end of the first year of life).
• Genital underdevelopment due to hypogonadism (sex hormone deficiency).
• Early graying of hair.

Hereditary Zinc Dependent Immunodeficiency

With hereditary zinc-dependent immunodeficiency, zinc ions are not absorbed into the small intestine due to a defect in a specific transport protein. In addition to combined immunodeficiency, enteropathic acrodermatitis develops with severe skin lesions, alopecia, gastrointestinal disorders and neurological disorders, thymic hypoplasia and plasma tissue lymph nodes. The introduction of zinc sulfate parenterally or orally in large doses restores the structure of the thymus gland, eliminates the above symptoms and prevents the fatal outcome of the disease. Zinc is a cofactor of many enzymes, including alkaline phosphatase, which is so common in body tissues. With a deficiency of zinc from the organs of the immune system, primarily the thymus suffers.

McCusick Metaphysial Chondrodysplasia

McCusick’s metaphysical chondrodysplasia ( “cartilage and hair hypoplasia” ) is characterized by short limbs due to impaired growth and maturation of cartilage, thin meager, pigment -free hair and moderately severe (rarely severe) combined immunodeficiency. Chickenpox is especially difficult in these patients, although they are relatively resistant to other viral infections. Some patients develop hypoplastic anemia .

Minor combined immunodeficiencies

The main disease in this group is general variable immune deficiency .

General variable immune deficiency (AVIN) - immunodeficiency, in which the production of various classes of immunoglobulins by plasma cells, as well as the activity of the T-link of immunity, is reduced. The disease is hereditary, but appears some time after birth, sometimes in the second or third decade of life. Clinically, AVIN is accompanied by chronic and frequent acute inflammatory processes in the ENT organs and respiratory tract.

Genetic defects that cause dysfunction of macrophages (histiocytes) and microphages (neutrophilic granulocytes) are the basis of the following diseases and syndromes:

I. Hereditary neutropenia

1. Kostman Agranulocytosis
2. Cyclic neutropenia
3. Hereditary acyclic ( permanent ) neutropenia .

II. Hereditary defects of chemotaxis, phagocytosis and bactericidal activity of scavenger cells

1. Chronic granulomatous disease in children
2. Miller's “lazy white blood cell” syndrome
3. Schwahman's syndrome
4. Chediak's syndrome - Higashi .

They are manifested by recurrent infections caused by pyogenic microflora (primarily staphylococci and intestinal bacteria). Most often, skin, lungs and mucous membranes of the oral cavity and intestines are affected.

Hereditary Neutropenia

Among hereditary neutropenia, Kostman's fatal agranulocytosis, cyclic and permanent neutropenia are distinguished. By neutropenia is meant a decrease in the content of neutrophilic granulocytes in peripheral blood of less than 1,500 cells per μl. However, this figure, acceptable for the population as a whole, is nonetheless conditional, as some people are characterized by a low level of neutrophils without any pathological changes in the body (this suggests that usually neutrophilic granulocytes are produced more than is required for effective antibacterial protection )

Costman Agranulocytosis

Kostman agranulocytosis is a serious disease in which myeloid tissue is not capable of producing granulocytes, especially neutrophilic ones. Since neutrophilic granulocytes are the central element of the body’s antibacterial defense, with Kostman’s disease, emerging bacterial infections are difficult and fatal in the first months of a child’s life.

Cyclic neutropenia

Cyclic neutropenia is a hereditary disease in humans and the gray Scottish Shepherd Dog, manifested in cyclical changes in the intensity of hematopoiesis. In this case, periodic fluctuations in the level are detected for all formed elements of the blood, including neutrophilic granulocytes. Moreover, neutrophils with their long maturity and short life time are characterized by the most obvious deviations in the form of 21-day ups and downs. The monocyte cycle has an inverse relationship - the number of these cells reaches a peak during a decrease in the number of neutrophils. An increase and decrease in the concentration of red blood cells and platelets is barely noticeable due to the significantly longer life span.

Chronic acyclic neutropenia

Hereditary chronic acyclic neutropenia manifests itself immediately after birth, that is, it is congenital . It is inherited in some cases as an autosomal dominant trait, in others as an autosomal recessive trait. May be accompanied by monocytosis and eosinophilia (alone or in combination). Acquired variants should be distinguished from hereditary variants of chronic acyclic neutropenia, in particular, autoimmune neutropenia (as a manifestation of autoimmune agranulocytosis or other autoimmune diseases), cirrhosis due to hypersplenism and transient neonatal neutropenia that develops when the mother responds to neutrophilic granulomas. In some cases, against the background of neutropenia, myeloid leukemia or aplastic anemia occurs.

Chemotaxis, Phagocytosis, and Bactericidal Defects

A number of hereditary diseases are characterized by a violation of chemotaxis, phagocytosis and bactericidal activity of neutrophilic granulocytes and macrophages. These defects are the basis of chronic granulomatous disease in children, Miller's syndrome and several other diseases.

Chronic granulomatous disease in children

Chronic granulomatous disease in children is a hereditary deficiency of the bactericidal function of phagocytes. Migration activity of cells and the ability to phagocytosis, as a rule, are not impaired. The disease was described in 1957. Microorganisms absorbed by cells do not break down in the phagolysosomes, remain viable and actively multiply ( endocytobiosis ). The defect in the bactericidal function of macrophages and neutrophils is due to the lack of enzymes for the synthesis of active oxygen radicals - NADP * H-oxidases , without which the phagocyte is not able to destroy the microbial cell. For the same reason (absence or low concentration of oxygen metabolites), the purulent exudate formed in the damaged tissue does not have lytic properties, therefore, for chronic granulomatous disease of children, diffuse purulent inflammation ( phlegmon ) is not characteristic, but abscesses occur, often multiple microabscesses (pustules and apostems) . In tissue sections stained with hematoxylin and eosin, many granules of golden pigment ( ceroid ) are detected in the cytoplasm of macrophages. Pigmented histiocytes help diagnose.

Miller's Lazy White Blood Cell Syndrome

Miller's “lazy white blood cell” syndrome is a combination of hereditary defects of neutrophilic granulocyte function:

• Insufficiency of migration activity (delayed chemotaxis)
• Decreased phagocytosis intensity (delayed chemotaxis and sluggish phagocytosis are the result of a dysfunction of the cytoskeleton, which provides cell locomotion and phagocytosis)
• Deficiency of bactericidal function, primarily due to a defect in the oxygen mechanism.

Syndrome of “lazy white blood cells” in combination with congenital insufficiency of exocrine pancreatic function is called Schwahman’s disease (Shreckman’s disease), with complete albinism - Chediak-Higashi’s disease (in this disease, giant cells are found in the cytoplasm of neutrophils, macrophages, monocytes and lymphocytes, granulocytes and lymphocytes there is a pathological aggregation of melanosomes underlying albinism).

Phagocytic Enzyme and Cytoskeletal Defects

In addition, hereditary defects of phagocytic enzymes and selective abnormalities in the functioning of cytoskeletal elements are described:

• Primary deficiency of myeloperoxidase and other enzymes
• Primary actin polymerization defect
• Tuftsin deficiency .

Primary myeloperoxidase deficiency of neutrophilic granulocytes and monocytes / macrophages is inherited in an autosomal recessive manner. In this case, there is no synthesis of other active oxygen metabolites (primarily the hydroxyl radical) and halogen-containing compounds from hydrogen peroxide. Eosinophilic granulocytes do not suffer. The clinical manifestations of the disease correspond to the chronic granulomatous disease of children , but they are much less severe, since the phagocytes do not lose the ability to form hydrogen peroxide . In addition, hereditary defects of NADH oxidase , glutathione peroxidase , glucose-6-phosphate dehydrogenase, neutrophilic granulocytes are known.

The primary defect in the actin polymerization in neutrophilic granulocytes is characterized by their loss of ability to locomotion and phagocytosis due to the blockade of the actin polymerization process necessary for the formation of pseudopodia and phagosomes.

An inherited defect in the formation of tafcin is manifested by chronic non-specific inflammatory diseases of the lungs and lymph nodes. The syndrome is inherited in an autosomal dominant manner. Tuftsin is a tetrapeptide (tyr-lys-pro-arg) released from the IgG molecule under the influence of specific proteases of phagocytes; it enhances the phagocytic activity of neutrophilic granulocytes.

The deficiency of complement proteins manifests itself in different ways depending on which (or which) proteins are absent.

There are three groups of diseases associated with primary complement deficiency:

1. Complement-dependent immunodeficiency syndromes
2. Complement-Associated Autoimmune Diseases
3. Quincke-Osler hereditary angioedema .

Complement Dependent Immunodeficiency Syndromes

Complement-dependent immunodeficiency syndromes are diseases accompanied by a lack of antibacterial protection of the body. They are manifested by frequent infectious processes in various organs and tissues. Since complement proteins, when activated, play the role of chemoattractants and opsonins, providing the effective function of phagocytic cells, secondary deficiency of macrophage and neutrophilic granulocyte function is formed when complement components are deficient. Especially often, infectious processes are caused by streptococci, in particular pneumococci, and Haemophilus influenzae . This group includes deficiency of a C3b inactivator, C3, C6 and C8 proteins.

Insufficiency of a C3b inactivator. The C3b inactivator plays the role of an inhibitor of an alternative complement activation pathway. In its absence, there is a rapid consumption of the C3 component ( secondary C3 deficiency ), which under normal conditions takes an active part in the antibacterial defense of the body. Protein C3 in patients in plasma is approximately 20% of the norm. However, it is 75% represented by the C3b fragment. The level of native C3 is only 5% of the norm. The rate of C3 cleavage in patients is increased by almost 5 times. It is shown that 2% after the injection of native C3, 40% of the introduced molecules undergo cleavage. In addition to secondary C3 deficiency, secondary C5 protein deficiency forms, however, it is less pronounced (approximately 40% of the normal level). The concentration of factor B is markedly reduced - 5% of the norm (factor B splitting occurs under the influence of factor D ). The level of properdine is slightly reduced. Patients with this disease suffer from various bacterial infections.

C3 deficiency. The insufficiency of the C3 component of complement is also manifested by various bacterioses. At the heart of the disease, in contrast to the deficiency of the C3b inactivator, is the primary deficiency of the C3 protein.

Complementary Autoimmune Diseases

Lack of complement proteins provokes the occurrence of autoimmune diseases , especially (1) lupus erythematosus , (2) the so-called lupus-like syndrome and (3) rheumatoid arthritis . Often, kidneys are affected by the type of glomerulonephritis. Patients also described Schonlein-Genoch purpura and polymyositis. These diseases include the deficiency of proteins C1, C2, C4 and C5. The genes of these proteins are linked to the genes of the immune response ( MHC genes ), so their defects are usually mutual.

Deficiency C2. C2 deficiency is the most common variant of primary complement protein deficiency. C2 is synthesized by fixed and vagus macrophages, whose phagocytic function is not impaired.

Quincke-Osler Hereditary Angioedema Edema

The third group of conditions associated with primary complement failure includes hereditary Quincke-Osler edema , which is based on C1-inhibitor deficiency. In some patients, autoimmune processes occur, especially lupus erythematosus.

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