Congenital disorders of immune regulation

The term diseases of immune dysregulation is an umbrella term for various diseases which stand out due to autoimmunity and/or lymphoproliferation of secondary lymphoid organs. The investigation of these diseases linked to single-gene defects provides an insight into different pathomechanisms of immune dysregulation or rather autoimmune phenomena. A defect of lymphocyte apoptosis in ALPS syndromes and an impairment of cellular cytotoxicity in hemophagocytic lymphohistiocytosis syndromes lead to lymphoproliferation, hepatosplenomegaly and autoimmune cytopenia. In addition a dysfunction in the development of immune tolerance causes autoimmune disease often with the involvement of endocrine organs. The APECED syndrome is caused by a disruption of central tolerance and shows in addition to autoimmune polyendocrinopathy a chronic mucocutaneous candidiasis. The defect in the development of peripheral tolerance in IPEX syndrome leads to a severe enteropathy in early childhood. The discovery of the responsible gene defects of these diseases and studies using the corresponding mouse models make an important contribution to the understanding of immune dysregulation and can possibly help in the development of new therapeutic strategies for these patients.