The Many Causes Of Immune Deficiency

The many different causes leading to defects of the immune system describes Congress President Professor Reinhold E. Schmidt, Clinic for Immunology and Rheumatology at Hanover Medical School, at the 2nd European Congress of Immunology in Berlin.

The most common causes worldwide include malnutrition, poor sanitary conditions and human immune deficiency virus (HIV) infection. Other causes of temporary or permanent damage to the immune system include old age, medications (e.g. cortisone, cytostatic drugs), radiotherapy, stress after surgery and malignant tumors of the bone marrow and the lymph nodes. Innate deficiencies of the immune system are comparatively rare. However, as experiments of nature, they allow insights into the structure and functioning of the human immune system. Innate immune deficiencies are estimated to occur in one out of 500 individuals.

Body surfaces serve as a reliable barrier to fend off most pathogens. Behind this barrier, there is an innate immune system (consisting of white blood cells such as macrophages, granulocytes, NK cells, dendritic cells), which uses a systematic search to identify various pathogens as dangerous and responds by immediately triggering an inflammatory reaction (swelling, redness, pain, fever). The overwhelming majority of pathogens will not survive this response. Only the most aggressive among them overcome the barrier of the innate immune system. To fight these off successfully, the body will need to resort to what is called the adaptive immune system (consisting of white blood cells of T cells and B cells). This is a back-up system, which not only eliminates specific pathogens but also develops a memory for future protection.

Over the past few years, a European registry for primary (innate) immunodeficiency diseases (PID) has been compiled supported by several national registries. By now, it contains anonymized information about more than 9,000 patients. These data are made available upon request for scientific analyses. About 65% of these innate immunodeficiencies are related to defects in antibody formation; 15-20% are severe combined immune defects caused by defects of T cell development and functioning. The rest are less prevalent defects of innate immunity cells and the complement system.

More than 150 different genetic defects (mutations, deletions, insertions and others) have already been described in innate immune deficiency patients; these are directly responsible for the occurrence of a defective immune response. New deficiencies are found almost every day. At the 2nd European Immunology Congress in Berlin (September 13-16, 2009), as many as four new genetic defects causing severe T cell malfunctions will be presented at the workshop “T cell deficiencies“.

In addition, there will be two satellite symposia on innate immunodeficiencies, one on Sunday afternoon, September 13, funded by CSL-Behring; the other on Tuesday afternoon, September 15, funded by Baxter. Many of these severe innate T cell deficiencies can be cured today using stem cell transplants. B cell deficiencies, which usually take a milder course, can be treated by regular administration of antibody preparations from the blood of healthy plasma donors to reduce susceptibility to infection dramatically.

The scientifically interesting PIDs are by far outnumbered by acquired immune deficiencies, caused by factors such as chronic viral infections (such as HIV or hepatitis C), undernutrition, polytrauma, stress after surgery, diabetes, cancer of the lymph nodes, anesthesia influences and others. Many of these secondary immunodeficiencies are treatable today. The ECI congress in Berlin will present many new findings in this area.

Finally, boundaries between immunodeficiency diseases and autoimmune diseases are blurred, because a number of T cell and B cell deficiencies cause not only increased susceptibility to infection, but also autoimmune phenomena. In order to find out more about these complex interconnections and to make a gradual transfer to the clinical routine, specialized centers are needed in which interdisciplinary teams of pediatricians, internal medicine specialists, immunologists, molecular biologists, infectiologists, hematologists, and pathologists work closely together both to study the causes of PID and to develop novel treatment methods. Such an integrated research and treatment Center for Chronic Immunodeficiency (CCI) is currently being established with the support of the Federal Ministry for Education and Research (BMBF) at Freiburg University Hospitals. Other immunodeficiency centers are located in Hanover, Ulm, Dresden, Krefeld, Munich, and Berlin.