Genetic Regulation of Serum Cytokines in Systemic Lupus Erythematosus

摘要

Genetic association studies in systemic lupus erythematosus (SLE) have been extremely successful in recent years, identifying a number of loci associated with disease susceptibility. Much work remains to integrate these loci into the functional pathogenic pathways which characterize the disease. Our working hypothesis is that many of the genetic variations linked to SLE and autoimmunity mediate risk of disease by altering cytokine profiles or responses to cytokine signaling. Genetic polymorphisms affecting cytokine signaling could alter thresholds for immune responses, resulting in pro-inflammatory presentation of self antigens and the subsequent misdirection of adaptive immunity against self which is observed in autoimmune disease. SLE is clinically heterogeneous and genetically complex, and we expect that individual genes and cytokine patterns will be more or less important to different disease manifestations and subgroups of patients. Defining these genotype-cytokine-phenotype relationships will increase our understanding of both initial disease pathogenesis as well as subsequent responseon-response to various therapies. In this review we summarize some recent work in the area of SLE cytokine genetics, and describe the implications for SLE, autoimmunity, and immune system homeostasis which are revealed by these investigations.