TY - JOUR
T1 - Genetic regulation of serum cytokines in systemic lupus erythematosus
AU - Kariuki, Silvia N.
AU - Niewold, Timothy B.
N1 - Funding Information:
Supported by National Institutes of Health Grant K08 AI083790 , NIAID Clinical Research Loan Repayment Grant AI071651 , Arthritis National Research Foundation Eng Tan Scholar Award , University of Chicago CTSA Core Subsidy Grant and Collaborative University of Chicago/Northshore University Health System Translational Research Pilot Grant RR024999 from UL1.
PY - 2010/3
Y1 - 2010/3
N2 - Genetic association studies in systemic lupus erythematosus (SLE) have been extremely successful in recent years, identifying several loci associated with disease susceptibility. Much work remains to integrate these loci into the functional pathogenic pathways that characterize the disease. Our working hypothesis is that many genetic variations linked to SLE and autoimmunity mediate the risk of disease by altering cytokine profiles or responses to cytokine signaling. Genetic polymorphisms that affect cytokine signaling could alter thresholds for immune responses, resulting in proinflammatory 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 response/nonresponse 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.
AB - Genetic association studies in systemic lupus erythematosus (SLE) have been extremely successful in recent years, identifying several loci associated with disease susceptibility. Much work remains to integrate these loci into the functional pathogenic pathways that characterize the disease. Our working hypothesis is that many genetic variations linked to SLE and autoimmunity mediate the risk of disease by altering cytokine profiles or responses to cytokine signaling. Genetic polymorphisms that affect cytokine signaling could alter thresholds for immune responses, resulting in proinflammatory 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 response/nonresponse 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.
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U2 - 10.1016/j.trsl.2009.08.012
DO - 10.1016/j.trsl.2009.08.012
M3 - Review article
C2 - 20171594
AN - SCOPUS:76549136591
SN - 1931-5244
VL - 155
SP - 109
EP - 117
JO - Translational Research
JF - Translational Research
IS - 3
ER -