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Impact of the leucocyte immunoglobulin-like receptor A3 (LILRA3) on susceptibility and subphenotypes of systemic lupus erythematosus and Sjögren's syndrome
  1. Yan Du1,
  2. Yin Su1,
  3. Jing He1,
  4. Yue Yang1,
  5. Yamei Shi2,
  6. Yong Cui3,
  7. Cainan Luo2,
  8. Xinyu Wu1,
  9. Xu Liu1,
  10. Fanlei Hu1,
  11. Xiaoxu Ma1,
  12. Li Zheng1,
  13. Jing Zhang1,
  14. Xianbo Zuo3,
  15. Yujun Sheng3,
  16. Lijun Wu2,
  17. Xuejun Zhang3,
  18. Jianping Guo1,
  19. Zhanguo Li1
  1. 1Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
  2. 2Department of Rheumatology and Immunology, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
  3. 3Department of Dermatology, Institute of Dermatology, No 1 Hospital, Anhui Medical University, Hefei, China
  1. Correspondence to Professor Jianping Guo, Department of Rheumatology and Immunology, Peking University People's Hospital, 11 South Xizhimen Street, Beijing 100044, China; jpguo99{at}gmail.com

Abstract

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.

  • Systemic Lupus Erythematosus
  • Sjögren's Syndrome
  • Gene Polymorphism

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