title: Impact of the leucocyte immunoglobulin-like receptor A3 (LILRA3) on susceptibility and subphenotypes of systemic lupus erythematosus and Sjögren's syndrome.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Dermatology, Institute of Dermatology, No 1 Hospital, Anhui Medical University, Hefei, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Rheumatology and Immunology, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
authors.forename: Cainan
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Fanlei
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Institute of Dermatology, No 1 Hospital, Anhui Medical University, Hefei, China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Dermatology, Institute of Dermatology, No 1 Hospital, Anhui Medical University, Hefei, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Department of Rheumatology and Immunology, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Institute of Dermatology, No 1 Hospital, Anhui Medical University, Hefei, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007970:Leukopenia / Q000097:blood / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics*; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000097:blood / Q000235:genetics* / Q000276:immunology; D013921:Thrombocytopenia / Q000097:blood / Q000235:genetics
chemical_list: D000974:Antibodies, Antinuclear; C530062:LILRA3 protein, human; D011971:Receptors, Immunologic; C035356:SS-A antibodies; C035357:SS-B antibodies
keywords: Gene Polymorphism; Sjögren's Syndrome; Systemic Lupus Erythematosus