Pathogenese des systemischen Lupus erythematodes

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with an extremely complex pathogenesis. Due to a genetic predisposition the disease can be induced by multiple stress factors involving epigenetic mechanisms and under the influence of the innate immune system. Defective clearance of immune complexes and apoptotic material together with enhanced neutrophil extracellular trap formation (NETosis) as well as up-regulation of type 1 interferon in particular, drive the adaptive immune system to a breakdown of self-tolerance. The result is a B cell hyperactivity, which leads to the generation of a multitude of different autoantibodies that are not only directed against nuclear antigens. Autoantibodies are the initiators for the involvement of many organs, which enhances further inflammatory cells and cytokines by participation of effector T-cells. Finally, an autoreactive immunological (plasma cell) memory is formed, which contributes to chronification and is associated with therapy-refractive courses of the disease. The depletion of the autoreactive immunological memory by immunoablation can lead to induction of self-tolerance and long-term remission.

Impact of folic acid on regulatory B lymphocytes from patients with systemic lupus erythematosus in vitro

“…Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by the production of autoantibodies against a vast number of host antigens 1 . Although genetic susceptibility has undoubtedly a key role in the development of the disease, 2 recent evidence revealed the participation of DNA methylation in the pathogenesis of this disorder 3 …”

“…1 Although genetic susceptibility has undoubtedly a key role in the development of the disease, 2 recent evidence revealed the participation of DNA methylation in the pathogenesis of this disorder. 3 Of particular interest is the DNA methylation status of B lymphocytes as B cell autoreactivity could be a consequence from aberrant…”

Lате Onset of Sle in Males: A Misdiagnosed Disease

“…The exact etiology of SLE is unknown [1][2][3]. Multiple genes contribute to disease susceptibility.…”

“…SLE shows a strong familial aggregation, with a much higher frequency among the first degree relatives of patients. Moreover, in extended families, SLE may coexist with other organ specific autoimmune diseases, such as hemolytic anemia, immune thrombocytopenic purpura, and thyroiditis [3].…”

“…Defective immune regulatory mechanisms, such as the clearance of apoptotic cells and immune complexes, are important contributors to the development of SLE. The loss of immune tolerance, increased antigenic load, excess helper T cells, defective B cell suppression, and the shifting of T helper 1 (Th1) to T helper 2 (Th2) immune responses lead to B cell hyperactivity and to production of pathogenic autoantibodies [1][2][3]. Finally, certain environmental factors are probably required to trigger the disease [1].…”