The Mosaic of Autoimmunity: Genetic Factors Involved in Autoimmune Diseases - ד"ר אוריאל כץ, Yehuda Shoenfeld, Boris Gilburd, Mahmud Abu-Shakra, Howar

A combination of various genetic, hormonal, immune, and environmental factors make up “Mosaic of Autoimmunity”. A better understanding of abnormalities in chromosomes and genes, defects in cells of immune system, hormonal changes leading to autoimmunity and environmental factors was achieved. Some more factors are added to the list because of novel therapeutic interventions. Non-HLA genes like  immune regulatory and tissue-specific genes play a crucial role in inducing autoimmunity. A general but low risk autoimmunity gene, CTLA-4 is associated with Graves’ disease and type 1 diabetes. Genes like CD40 and NOD2 were found to be involved with high immunoglobulin E levels in asthma and Crohn’s disease. respectively. Tissue-specific like genes thyroid-stimulating hormone receptor gene and the major thyroid protein, thyroglobulin, have been found to be strongly associated with thyroid autoimmunity. The mechanism of the most common primary immunodeficiency in humans, selective IgA deficiency which is characterized by very low serum IgA levels and normal levels of all other immunoglobulins, has been elucidated in details. Also, secondary IgA deficiency is reported to be caused by drugs such as D-penicillamine, sulfasalazine and gold. Various autoimmune diseases accompanying selective IgA deficiency are SLE, rheumatoid arthritis, juvenile rheumatoid arthritis, Still’s disease, type I diabetes, myasthenia gravis, celiac disease and Crohn’s disease. The use of anti-IgA antibodies increases the risk of severe reactions to blood products. Since autoimmune disorders are seen to be occuring more frequently in individuals with selective IgA deficiency than in the general population, the treatment of patients with selective IgA deficiency should be directed to the accompanying disease. Also, levels of IgA should be determined in every patient with an autoimmune disease and specially in those individuals who are at the risk of developing an autoimmune condition in the future. The knowledge of all the factors mentioned above can help in achieving this goal successfully. Since IgA levels have been associated with the progression of different cancers also, the development of such ‘mosaic’ for cancer might give a new direction to the therapeutics.