Antibody deficiency syndromes (humoral immunodeficiencies)

They make up 50-75% of all primary immunodeficiencies. This group includes deficiencies of immunoglobulins of one or more classes.

The clinical picture of antibody formation defects is milder than that of combined immune deficiency, however, in some cases, these are serious diseases with a serious, often unfavorable prognosis. Symptoms appear, as a rule, from the second half of the child’s life, since in the first 4-6 months of life the child is protected by maternal antibodies.

The main symptom is recurrent respiratory tract infections. Bacterial infections caused by encapsulated bacteria predominate: staphylo-, pneumo-, streptococci, Haemophilus influenzae. Sensitivity to enterococci and gram-negative bacteria is less pronounced. The upper and lower respiratory tract are primarily affected.

Bruton’s disease (X-linked agammaglobulinemia, hereditary agammaglobulinemia) (1-5: 1000 0000). X-linked disease.

Reason: mutation of the Btk gene on the X chromosome leads to a deficiency of the enzyme tyrosine kinase with a delay in the proliferation and differentiation of B-lymphocytes.

Age of manifestation : 4 months-2 years, gender : male

Key clinical and laboratory features:

1. Recurrent sinopulmonary infections (8 or more otitis media/year, 2 or more severe sinusitis/year, 2 or more pneumonia/year)

2. Persistent diarrhea (Giardia lamblia, Campylobacter jeunii)

3. Purulent infections of the skin and soft tissues (furunculosis, abscesses, phlegmon)

4. Hypoplasia of palatine tonsils, lymph nodes

5. A persistent decrease in the concentrations of all immunoglobulins – IgG, IgA, IgM, IgD, IgE. IgG<2.0 g/l, IgA, IgM<0.2 g/l. The sum of immunoglobulins is less than 2 g/l.

6. A sharp decrease in the fraction of gamma globulins (<10%)

7. Profound B-lymphocyte deficiency (CD19 + <1-2%)

The disease manifests itself at the age of 4 months-2 years, the leading in the clinical picture are recurrent sinopulmonary infections (otitis media, sinusitis, bronchitis, pneumonia) caused by pneumococcus, Haemophilus influenzae, Staphylococcus aureus . By the age of 3-5, most patients develop chronic sinusitis, chronic pneumonia, and subsequently bronchiectasis. 1/3 of patients develop chronic gastroenteritis (Giardia lamblia, Campylobacter jeunii). Arthritis of mycoplasmal etiology is possible. Resistance to viral infections is preserved, some patients develop enteroviral meningoencephalitis, post-vaccination poliomyelitis. Neoplasias are rare.

Treatment: antibacterial drugs, if necessary – permanent or intermittent AB therapy. Patients with chronic bronchopulmonary infections are shown daily vibration massage and postural drainage, with exacerbations – sanation bronchoscopy. The main method of treatment is lifelong replacement therapy with immunoglobulin preparations (Gamunex, Octagam, Intraket, Gamimun). In children with a newly diagnosed diagnosis, substitution therapy is carried out in a saturation mode of 0.1-0.2 g / kg 2 times a week. When the IgG level is not lower than 4.0-6.0 g/l, they switch to a maintenance dose of 0.1-0.2 g/kg once a month. Domestic preparations of immunoglobulins are not recommended due to poor purification and the inability to administer a therapeutic dose.

Prognosis: Relatively favorable with early diagnosis and regular replacement therapy.

Common Variable Immunodeficiency (CVID) (Acquired Agammaglobulinemia) (1:50,000 – 1:200,000). Various types of inheritance are possible: autosomal recessive, autosomal dominant, X-linked, sporadic cases.

Reason: not fully known. The disease is accompanied by a violation of the maturation of B-lymphocytes into cells that synthesize antibodies (plasma cells).

Age of onset : any age with early peaks, ages 6-10 and 26-30, sex : both

Key clinical and laboratory features:

1. Recurrent sinopulmonary infections (H.influenzae, Str. pneumoniae)

2. Persistent diarrhea (Giardia lamblia, Campylobacter jeunii)

3. Purulent infections of the skin and soft tissues (furunculosis, abscesses, phlegmon)

4. A persistent decrease in the concentration of immunoglobulins – IgG<2.5 g/l, a decrease - IgA, IgM. Their sum is less than 3 g/l.

5. The level of B-lymphocytes (CD19 + ) is normal or moderately reduced

The main symptoms are similar to Bruton’s disease. Recurrent infections of the upper respiratory tract and respiratory tract are characteristic. Most patients develop chronic bronchitis with copious purulent sputum and a continuous course, chronic pneumonia, chronic purulent sinusitis or maxillary etmoiditis. Infectious and inflammatory diseases of the skin and subcutaneous tissue (streptoderma, furunculosis) are characteristic. 1/3 of patients have a persistent diarrheal syndrome. Resistance to viral infections is generally preserved, however, there are cases of severe enteroviral polyradiculoneuritis and post-vaccination poliomyelitis.

Differences from Bruton’s disease : increased frequency of lymphomas, autoimmune diseases (SLE, autoimmune thrombocytopenia, arthritis, thyroiditis).

Treatment: antibacterial drugs in high doses for up to 21 days, if necessary – for a long time. Patients suffering from chronic bronchopulmonary infections are shown daily vibration massage and postural drainage, with exacerbations – sanitation bronchoscopy. The main method of treatment is lifelong replacement therapy with immunoglobulin preparations (Gamunex, Octagam, Intraket, Gamimun). With newly diagnosed CVID, substitution therapy is carried out in the saturation mode of 0.1-0.2 g/kg 2 times a week. When the IgG level is not lower than 4.0-6.0 g/l, they switch to a maintenance dose of 0.1-0.2 g/kg once a month.

Prognosis: Relatively determined by the presence of autoimmune pathology, severe infections and malignant neoplasms. With regular replacement therapy, the prognosis is relatively favorable.

Selective deficiency of immunoglobulin A (1:500-1:1000 in the Caucasoid population, 1:4000-1:20,000 in the Mongoloid). Most cases are sporadic.

Reason : The exact genetic defect is not known. Plasma cells secreting IgA are not formed. Perhaps the formation of autoantibodies to IgA.

Age : no clear onset. Gender: both.

Key clinical and laboratory features:

1. In some cases, it is asymptomatic

2. Repeated SARS, nasopharyngitis, bronchitis, infections of the upper respiratory tract

3. Normal cellular immunity (CD3 + , CD4 + , CD8 + )

4. IgA decrease less than 0.05 g/l, IgM, IgG levels are normal

Patients with selective IgA deficiency may be clinically healthy, but in a significant proportion of cases they suffer from recurrent viral and bacterial infections of the upper and middle respiratory tract, which are much milder than in patients with total AT deficiency. There may be repeated infections of the skin in the form of boils, barley, felons. An increased frequency of allergic diseases is characteristic – atopic dermatitis, hay fever, food allergies. In most patients with age, compensation of immune deficiency and a decrease in respiratory morbidity are noted. Some patients develop autoimmune diseases – juvenile RA, scleroderma, thyroiditis, vitiligo.

Treatment: the disease belongs to uncorrected primary IDS. Secondary complications of an infectious, allergic and autoimmune nature are treated. According to the indications, activation of the preserved links of immunity (bacterial lysates) is carried out. Replacement therapy with IV immunoglobulins is not recommended. Since patients often have anti-IgA autoantibodies, the administration of immunoglobulin preparations can cause hypersensitivity reactions.

Forecast for life : favorable

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