Background Several studies have reported that the 6.7-kb LILRA3 deletion was associated with multiple sclerosis (MS) and SS in Caucasians [1-3]. However, whether the 6.7-kb LILRA3 deletion also contributes to autoimmune susceptibility in other ethnicityspecific population(s), and whether the variant is a novel genetic risk for other autoimmune diseases, e.g. SLE, has not been determined. We undertook the current study to investigate the possible association between LILRA3 deletion and pSS or SLE in Han population. Unexpectedly, we found that the non-deleted (functional) LILRA3 rather than deleted (nonfunctional) LILRA3 was strongly associated with both pSS and SLE in Han population. To our knowledge, this is the first study we demonstrated that the functional LILRA3 is a novel susceptibility factor for autoimmune diseases, i.e. pSS and SLE.
Objectives The 6.7-kb deletion of leukocyte immunoglobulin-like receptor A3 (LILRA3) has conferred susceptibility to Sjögren's syndrome (SS) in Caucasians. Our initial aim was to investigate whether LILRA3 deletion was associated with primary SS in Han population and whether LILRA3 deletion was a novel genetic risk for systemic lupus erythematosus (SLE).
Methods The LILRA3 deletion and its tagging SNP rs103294 were genotyped in 403 pSS patients, 1099 SLE patients and 2169 healthy controls. Association analyses were performed as whole dataset or clinical/serologic subsets. The impact of LILRA3 on SLE activity and LILRA3 expression were evaluated.
Results Unexpectedly, a higher frequencies of the non-deleted (functional) LILRA3 were observed in both pSS (11.4%, P=1.40×10-3, OR=2.32) and SLE patients (12.7%, P=3.51×10-7, OR=2.03), compared with healthy individuals (6.2%). Functional LILRA3 was associated with almost all of clinical/serologic features in SLE, especially with leucopenia (P=4.09×10-7, OR=2.19) and thrombocytopenia (P=1.68×10-5, OR=1.70). It appeared highly associate with leucopenia (P=4.39×10-4, OR=3.25), anti-Ro/SSA-positive (P=4.54×10-3, OR=2.34) and anti-La/SSB-positive subphenotypes in pSS (P=0.012, OR=2.49). Functional LILRA3 conferred higher disease activity in SLE (P=0.044) and higher LILRA3 expression in both SLE (P=5.57×10-8) and pSS (P=1.49×10-7).
Conclusions Our study provides the first evidence that the functional LILRA3 is a novel genetic risk for pSS and SLE. It appears to highly predispose to certain phenotypes such as leucopenia and thrombocytopenia in SLE, and may confer increased disease activity in SLE and higher risk to leucopenia and autoantibody-positive subphenotypes in pSS.
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Acknowledgements We thank all the members and staff for recruiting patients and healthy controls and the technical assistance from Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing, China. We wish to thank the patients and healthy volunteers for their cooperation and for giving consent to participate in this study
Disclosure of Interest None declared