Impact of the leucocyte immunoglobulin-like receptor A3 (LILRA3) on susceptibility and subphenotypes of systemic lupus erythematosus and Sjögren's syndrome.

BACKGROUND:Recently, our research group identified the non-deleted (functional) leucocyte immunoglobulin-like receptor A3 (LILRA3) as a new genetic risk for rheumatoid arthritis. OBJECTIVES:To further investigate whether the functional LILRA3 is a new susceptibility factor for other autoimmune diseases-for example, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). METHODS:The LILRA3 deletion polymorphism and its tagging single nucleotide polymorphism rs103294 were genotyped for 1099 patients with SLE, 403 patients with pSS and 2169 healthy controls. Association analyses were performed in whole dataset or clinical/serological subsets. The impact of LILRA3 on SLE activity and LILRA3 expression was evaluated. RESULTS:The functional LILRA3 conferred high susceptibility to both SLE (p=3.51×10(-7), OR=2.03) and pSS (p=1.40×10(-3), OR=2.32). It was associated with almost all the clinical/serological features in SLE, especially with leucopenia (p=4.09×10(-7), OR=2.19) and thrombocytopenia (p=1.68×10(-5), OR=1.70). In pSS, functional LILRA3 was specifically associated with leucopenia (p=4.39×10(-4), OR=3.25), anti-Ro/SSA-positive subphenotypes (p=4.54×10(-3), OR=2.34) and anti-La/SSB-positive subphenotypes (p=0.012, OR=2.49). Functional LILRA3 conferred higher disease activity in patients with SLE (p=0.044) and higher LILRA3 expression in both SLE (p=5.57×10(-8)) and pSS (p=1.49×10(-7)) than in controls. CONCLUSIONS:Functional LILRA3 is a new susceptibility factor for SLE and pSS. It highly predisposes to certain phenotypes such as leucopenia and thrombocytopenia in SLE, and may confer increased disease activity in SLE and a higher risk of leucopenia and autoantibody-positive subphenotypes in pSS.

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