Serum Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3) Is Increased in Patients with Multiple Sclerosis and Is a Strong Independent Indicator of Disease Severity; 6.7kbp LILRA3 Gene Deletion Is Not Associated with Diseases Susceptibility.
Serum Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3) Is Increased in Patients with Multiple Sclerosis and Is a Strong Independent Indicator of Disease Severity; 6.7kbp LILRA3 Gene Deletion Is Not Associated with Diseases Susceptibility.
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多发性硬化症患者血清白细胞免疫球蛋白样受体 A3 (LILRA3) 升高，是疾病严重程度的一个强有力的独立指标； 6.7kbp LILRA3 基因缺失与疾病易感性无关。
DOI：
10.1371/journal.pone.0149200
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Tedla N
中科院分区：
文献类型：
--
作者：
An H;Lim C;Guillemin GJ;Vollmer-Conna U;Rawlinson W;Bryant K;Tedla N
白细胞免疫球蛋白样受体A3 （LILRA3）是一种主要由单核细胞和巨噬细胞表达的可溶性免疫调节分子。一个6.7kbp的纯合子LILRA3基因缺失，去除其8个外显子中的前7个，预计会导致LILRA3蛋白缺乏，尽管这尚未得到实验证实。此外，在不同的欧洲人群中，关于LILRA3纯合基因缺失与多发性硬化症（MS）易感性之间的联系，存在相互矛盾的结果。本研究的目的是调查LILRA3基因缺失是否与北美欧洲血统队列中的MS易感性相关，并评估血清LILRA3蛋白水平是否为MS临床亚型和/或疾病严重程度的标志。共有456名MS患者和99名无关的健康对照，通过内部夹心ELISA检测了6.7kbp的LILRA3基因缺失和血清中LILRA3蛋白水平。我们发现LILRA3基因缺失与MS易感性无关，也不影响发病年龄、临床亚型或疾病严重程度。然而，我们首次发现纯合子LILRA3基因缺失导致LILRA3蛋白缺乏产生。重要的是，与对照组相比，MS患者血清中LILRA3蛋白水平显著升高，特别是在更严重的原发性进行性MS中，多因素回归分析显示，血清中LILRA3蛋白水平是MS疾病严重程度最强的独立标志物之一，有可能作为诊断标志物。
Leukocyte immunoglobulin-like receptor A3 (LILRA3) is a soluble immune regulatory molecule primarily expressed by monocytes and macrophages. A homozygous 6.7kbp LILRA3 gene deletion that removes the first seven of its eight exons is predicted to lead to lack of LILRA3 protein, although this has not been experimentally confirmed. Moreover, there are conflicting results with regards to the link between the LILRA3 homozygous genetic deletion and susceptibility to multiple sclerosis (MS) in different European populations. The aim of this study was to investigate whether LILRA3 gene deletion is associated with MS susceptibility in a North American cohort of European ancestry and assess if serum LILRA3 protein level is a marker of clinical subtype and/or disease severity in MS. A total of 456 patients with MS and 99 unrelated healthy controls were genotyped for the 6.7kbp LILRA3 gene deletion and levels of LILRA3 protein in sera determined by in-house sandwich ELISA. We showed that LILRA3 gene deletion was not associated with MS susceptibility and did not affect the age of disease onset, clinical subtype or disease severity. However, we discovered for the first time that homozygous LILRA3 gene deletion results in lack of production of LILRA3 protein. Importantly, LILRA3 protein level was significantly increased in sera of patients with MS when compared with control subjects, particularly in more severe type primary progressive MS. Multiple regression analysis showed that LILRA3 level in serum was one of the strongest independent markers of disease severity in MS, which potentially can be used as a diagnostic marker.