Impact of the leucocyte immunoglobulin-like receptor A3 (LILRA3) on susceptibility and subphenotypes of systemic lupus erythematosus and Sjogren's syndrome
Impact of the leucocyte immunoglobulin-like receptor A3 (LILRA3) on susceptibility and subphenotypes of systemic lupus erythematosus and Sjogren's syndrome
复制标题
白细胞免疫球蛋白样受体 A3 (LILRA3) 对系统性红斑狼疮和干燥综合征易感性和亚表型的影响
DOI：
10.1136/annrheumdis-2013-204441
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发表时间：
2015-11-01
影响因子：
27.4
通讯作者：
Li, Zhanguo
中科院分区：
文献类型：
--
作者：
Du, Yan;Su, Yin;Li, Zhanguo
目的进一步探讨功能性LILRA3是否是系统性红斑狼疮(SLE)和原发性干燥综合征(PSS)等自身免疫性疾病的新易感因素。方法对1099例SLE患者、403例PSS患者和2169例健康对照进行LILRA3基因缺失及其标记单核苷酸多态rs103294基因分型。关联分析在整个数据集或临床/血清学子集中进行。结果功能性LILRA3对SLE(p=3.51x10(-7)，OR=2.03)和PSS(p=1.40x10(-3)，OR=2.32)具有较高的易感性。它与SLE的几乎所有临床/血清学特征有关，尤其是白细胞减少(p=4.09x10(-7)，OR=2.19)和血小板减少(p=1.68x10(-5)，OR=1.70)。在pSS中，功能性LILRA3与白细胞减少症(p=4.39x10(-4)，OR=3.25)、抗Ro/SSA阳性亚型(p=4.54x10(-3)，OR=2.34)和抗La/sSb阳性亚型(p=0.012，OR=2.49)特异性相关。功能性LILRA3在系统性红斑狼疮患者中的疾病活动性较高(p=0.044)，在系统性红斑狼疮(p=5.57x10(-8))和pSS(p=1.49x10(-7))中的表达均高于对照组。它高度易感于SLE中的某些表型，如白细胞减少和血小板减少，并可能使SLE疾病活动性增加，在PSS中出现白细胞减少和自身抗体阳性亚型的风险更高。
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 Sjogren'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=3.51x10(-7), OR=2.03) and pSS (p=1.40x10(-3), OR=2.32). It was associated with almost all the clinical/serological features in SLE, especially with leucopenia (p=4.09x10(-7), OR=2.19) and thrombocytopenia (p=1.68x10(-5), OR=1.70). In pSS, functional LILRA3 was specifically associated with leucopenia (p=4.39x10(-4), OR=3.25), anti-Ro/SSA-positive subphenotypes (p=4.54x10(-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=5.57x10(-8)) and pSS (p=1.49x10(-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.