Variable immunodeficiency syndrome

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Classification according to ICD-10
D83 Variable immunodeficiency (common variable immunodeficiency)
D83.0 Variable immunodeficiency with predominant deviations in the number and function of B cells
D83.1 Variable immunodeficiency with predominant immunoregulatory T-cell disorders
D83.2 Variable immunodeficiency with autoantibodies against B or T cells
D83.8 Other variable immunodeficiencies
D83.9 Variable immunodeficiency, unspecified
ICD-10 online (WHO version 2019)

The variable immunodeficiency syndrome (also antibody deficiency syndrome , English Common Variable Immunodeficiency; CVID ) is the most common congenital (primary) immune defect leading to a symptomatic disease in humans . It is mainly characterized by the lack of a certain class of antibodies , the immunoglobulin . The exact cause of the disease is unknown, but it is most likely a heterogeneous group of different individual diseases. Affected patients usually suffer from an accumulation of respiratory infections , along with a variety of other possible symptoms. In addition to infections of various parts of the body (mainly caused by bacteria), this also includes autoimmune phenomena and cancer. The disease is usually treated with immunoglobulin G infusions.

causes

According to the current state of research, the exact cause can only be determined in very few cases of variable immunodeficiency syndrome. Mutations in the TNFRSF13B gene on chromosome 17 gene locus p11.2, which are causally associated with the variable immunodeficiency syndrome, have been found in some of those affected . Both familial and sporadic forms of the disease occur.

Overall, it can be assumed that the variable immunodeficiency syndrome is a heterogeneous group of different individual diseases with different causes, most of which are not yet known.

Frequency and occurrence (epidemiology)

The frequency of variable immunodeficiency syndrome in Germany is estimated at 1 per 25,000 people, the estimates for industrialized nations are between 1: 10,000 and 1: 100,000. It is assumed that between 800 and 3,200 people are affected in Germany. Overall, it is a rare disease, even if it is one of the most common congenital immune defects.

There are two “peaks” in the age distribution at the time of diagnosis: the early form is usually found in toddlers, the late form in young adulthood.

Clinic and Symptoms

The symptoms of variable immunodeficiency syndrome can be assigned to the following groups: infections, disorders of the gastrointestinal tract, chronic respiratory diseases, skin symptoms, changes in lymphatic tissue, granulomas , autoimmune phenomena and tumors.

Infections:

Gastrointestinal disorders:

  • Diarrhea (about 1/3 of patients)
  • insufficient absorption of nutrients ( malabsorption )

Chronic respiratory diseases:

Changes in lymphoid tissue:

Granulomas:

  • Foci of inflammation with a certain structure in internal organs such as the liver, spleen, lungs and bone marrow

Autoimmune phenomena:

Skin symptoms:

Tumors :

diagnosis

Serum electrophoresis of a healthy person (schematic)
Serum electrophoresis of a CVID patient (schematic)

The suspicion of a variable immunodeficiency syndrome often results from recurring infections of the respiratory tract. However, it can also be an incidental finding that arises from serum electrophoresis or a determination of the immunoglobulins for other reasons. As a rule, a reduction in the gamma globulin fraction is already noticeable in the serum electrophoresis in affected patients.

First, the suspected diagnosis is made by quantitative determination of the immunoglobulins. The immunoglobulin G in the serum is always low, as a rule it is below 3 g / l. The immunoglobulins A and M are often also reduced. An essential component of the diagnosis is therefore a lack of antibodies in the blood.

In order to be able to make a definitive diagnosis of variable immunodeficiency syndrome, other possible causes of the antibody deficiency must be ruled out. These include B. a monoclonal increase of immunoglobulin light chains ( Bence Jones myeloma ), a strong loss of protein via the kidneys ( nephrotic syndrome ) or the intestine ( exudative enteropathy ).

In addition, some special immunological investigations are necessary, such as the determination of the immunoglobulin G subclasses, the flow cytometric analysis of the peripheral blood lymphocytes and the measurement of the specific antibody production.

Differential diagnosis

therapy

Treatment is only necessary for patients who suffer from symptoms from the disease. A preventive treatment in asymptomatic patients is not indicated. The regular intravenous or subcutaneous infusion of immunoglobulins (abbreviated IVIG or SCIG) is an effective treatment option. The intravenous infusions are administered every 2-6 weeks at a dose of 200 to 600 mg per kg of body weight. With subcutaneous infusions, much smaller amounts can be administered each week. The aim of this treatment is to keep the immunoglobulin G in the serum always above 5 g / l. In addition, all bacterial infections that occur as part of the disease are treated with antibiotics . The dosage of the antibiotic is much higher and the intake takes much longer than in normal patients.

forecast

Overall, it is not to be expected that patients with variable immunodeficiency syndrome will have a similar life expectancy as healthy people. However, the data on this is sparse. The following factors are mentioned in the literature that limit the prognosis of the disease: tumors, serious autoimmune phenomena and chronic respiratory diseases (bronchiectasis).

With the introduction of IVIG therapy, the prognosis for the disease has improved significantly over the past few decades.

literature

  • Mark Ballow: Primary immunodeficiency disorders: Antibody deficiency . In: J Allergy Clin Immunol . Vol. 109, No. 4, 2002, pp. 581-591, ISSN  0091-6749
  • Lennart Hammarström, Igor Vorechovský and David B. Webster: Selective IgA Deficiency (SIgAD) and common variable immunodeficiency (CVID) . In: Clin Exp Immunol . Vol. 120, 2000, pp. 225-231, ISSN  0009-9104
  • Hans-Hartmut Peter, Werner J. Pichler (Ed.): Clinical Immunology . 2nd Edition. Urban and Schwarzenberg, Munich; Vienna; Baltimore 1996, ISBN 3-541-14892-6
  • Fred S. Rosen et al .: Primary Immunodeficiency Diseases. Report of an IUIS Scientific Committee . In: Clin Exp Immunol . Vol. 118 (Suppl. 1), 1999, pp. 1-28, ISSN  0009-9104

Web links

Individual evidence

  1. ↑ Ulrich Salzer et al .: Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans . In: Nature Genetics . Vol. 37, 2005, pp. 820-828, ISSN  1061-4036