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Description: This document relates to materials and methods for diagnosing or predicting risk of systemic lupus erythematosus.BACKGROUND Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease characterized by antinuclear autoantibodies and deposition of immune complexes, leading to organ damage and early death (Alarcon-Segovia et al. (2005) ArthritisRheum. 52:1138-1147). SLE autoantibodies mediate organ damage by directly binding to host tissues and by forming immune complexes that deposit in vascular tissues and activate immune cells. Organs targeted in SLE include the skin, kidneys,vasculature, joints, various blood elements, and the central nervous system (CNS). The severity of disease, the spectrum of clinical involvement, and the response to therapy vary widely among patients. The type I interferon (IFN) pathway is activated in human SLE (Blanco et al. (2001) Science 294:1540-1543; Ronnblom and Alm (2001) J. Exp. Med. 194:F59-63; Baechler et al. (2003) Proc. Natl. Acad. Sci. USA 100:2610-2615). Type I IFN is acentral mediator of viral immunity (Isaacs and Lindenmann (1957) Proc. R. Soc. B 147:258-273), and many SLE patients strongly overexpress IFN-responsive genes in blood cells (Baechler et al. supra; Bennett et al. (2003) J. Exp. Med. 197:711-723;Kirou et al. (2004) Arthritis Rheum. 50:3958-3967). However, it is not known whether the IFN expression signature is a general biomarker of a dysregulated immune system, or rather reflects primary genetic variation causal to the pathogenesis of humanSLE. IFN regulatory factor 5 (IRF-5) is a member of a family of transcription factors that controls inflammatory and immune responses (Honda et al. (2005) Int. Immunol. 17:1367-1378). IRF-5 has a critical role in the production of thepro-inflammatory cytokines tumor necrosis factor-.alpha. (TNF-.alpha.), interleukin-12 (IL-12), and IL-6 following toll-like receptor (TLR) signaling as determined by knockout mouse studies (Takaoka et al.