Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Immunodeficiency Disorders

Extrapolations suggest that in Europe approx. 1.5 million individuals live with an inherited, primary immunodeficiency (PID). Despite modern antibiotic treatment, affected patients suffer from frequent infections which are hard to control. In Germany alone, the estimated number of affected persons exceeds 100,000; however, only approximately 2,000 patients have so far been diagnosed. Among all European countries, Germany ranks only second last regarding the percentage of diagnosed PID, although establishing a diagnosis early would be crucial to enhance the prognosis and life quality of patients significantly. By now, new diagnostic procedures and improved treatment (e.g. regular administration of antibodies, enzyme replacement therapy, modern antibiotics or antimycotics, the transplantation of stem cells from the bone marrow or peripheral blood or gene-based therapeutic approaches) have become available.

The term immune disorder (synonym: immunodeficiency) describes various disorders of the immune system. They are characterized by temporary or irreversible disorder of the body’s defence system. An immune disorder is termed inherited or primary if the immunodeficiency - for example due to a genetic variant or mutation - is congenital, runs in the family and/or is inherited. Secondary immunodeficiency, however, is an acquired disorder of the immune system; a common example is AIDS (acquired immune deficiency syndrome).

During the last few years, progress in the sector of molecular genetics and immunology has led to an increase in the identification of genes causing PID. Currently, we know of more than 150 different primary immunodeficiency disorders. According to the International Union of Immunological Societies (IUIS), there are 8 categories:

  1. Immunodeficiency with a severe lack in antibodies (e.g. agammaglobulinemia, common variable immunodeficiency [CVID])
  2. T and B cell defects (e.g. Severe Combined Immunodeficiency [SCID])
  3. Other well defined immunodeficiency syndromes (e.g. Wiskott Aldrich syndrome)
  4. Disorders of the immune regulation (e.g. X-bound lymphoproliferative syndrome, APECED syndrome)
  5. Defects of the number and function of phagocytes (e.g. severe congenital neutropenia)
  6. Defects of the natural immunity (e.g. chronic mucocutaneous candidiasis)
  7. complement deficiencies
  8. autoinflammatory diseases: they do not, however, display the major signs and symptoms of increased susceptibility (e.g. periodic fever syndromes)

Laboratory diagnostics initially involve a number of tests, including hematological and cytometric examinations of the blood. The chromosomal locations as well as the responsible genes of the majority of the inherited immunodeficiencies have by now been characterized (e.g. IL-2Rγ chain in position Xq13.1) and can therefore be directly analyzed. Some disorders cause a reduction or an increase in the expression of the gene product (e.g. CD45); these changes can be analyzed by immunoassays and/or flow cytometry. Today, there is a wide range of diagnostic options available at DNA as well as RNA and protein level. Therefore, in most cases, the exact diagnosis of an immunodeficiency can be established.