Genetic regulation of serum cytokines in systemic lupus erythematosus

Transl Res. 2010 Mar;155(3):109-17. doi: 10.1016/j.trsl.2009.08.012. Epub 2009 Sep 25.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Child
  • Cytokines / blood*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Interferon-alpha / blood
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Osteopontin / blood
  • Osteopontin / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics
  • STAT4 Transcription Factor / genetics
  • Sex Factors
  • Tumor Necrosis Factor-alpha / blood


  • Cytokines
  • Interferon-alpha
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • Tumor Necrosis Factor-alpha
  • Osteopontin
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22