HLA 相关性在荷兰人群中枢神经系统 MOG-IgG 和 AQP4-IgG 相关疾病中的作用。
HLA association in MOG-IgG- and AQP4-IgG-related disorders of the CNS in the Dutch population.
机构信息
From the Department of Neurology (A.L.B., Y.Y.M.W., E.D.P., R.Q.H., R.F.N., B.H.A.W.), Erasmus University Medical Center, Rotterdam; and Department of Immunohaematology and Blood Transfusion (P.J.E.L., G.W.H., F.H.J.C.), Leiden University Medical Center, the Netherlands.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2020 Mar 20;7(3). doi: 10.1212/NXI.0000000000000702. Print 2020 May.
OBJECTIVE
To investigate the possible human leukocyte antigen (HLA) association of both myelin oligodendrocyte glycoprotein (MOG-IgG)-associated diseases (MOGAD) and aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) in the Dutch population with European ancestry to clarify similarities or differences in the immunogenetic background of both diseases.
METHODS
Blood samples from patients in the Dutch national MS/NMOSD expert clinic were tested for MOG-IgG and AQP4-IgG using a cell-based assay. HLA Class I and II genotyping was performed in 43 MOG-IgG-seropositive and 42 AQP4-IgG-seropositive Dutch patients with European ancestry and compared with those of 5,604 Dutch healthy blood donors.
RESULTS
No significant HLA association was found in MOG-IgG-seropositive patients. The AQP4-IgG-seropositive patients had a significant higher frequency of HLA-A01 (61.9% vs 33.7%, OR 3.16, 95% CI, 1.707-5.863, after correction [c] = 0.0045), HLA-B08 (61.9% vs 25.6%, OR 4.66, 95% CI, 2.513-8.643, c < 0.0001), and HLA-DRB1*03 (51.2% vs 27.6%, OR 2.75, 95% CI, 1.495-5.042, c = 0.0199) compared with controls.
CONCLUSIONS
The present study demonstrates differences in the immunogenetic background of MOGAD and AQP4-IgG-positive NMOSD. The strong positive association with HLA-A01, -B08, and -DRB1*03 is suggestive of a role of this haplotype in the etiology of AQP4-IgG-positive NMOSD in patients with European ancestry, whereas in MOGAD no evidence was found for any HLA association in these disorders.
目的
研究荷兰具有欧洲血统的人群中髓鞘少突胶质细胞糖蛋白（MOG）-IgG 相关疾病（MOGAD）和水通道蛋白 4 抗体（AQP4-IgG）阳性视神经脊髓炎谱系疾病（NMOSD）之间可能存在的人类白细胞抗原（HLA）关联，以阐明这两种疾病的免疫遗传背景的相似性或差异性。
方法
使用基于细胞的测定法，对荷兰国家多发性硬化症/NMOSD 专家诊所的患者血液样本进行 MOG-IgG 和 AQP4-IgG 检测。对 43 例 MOG-IgG 阳性和 42 例 AQP4-IgG 阳性的欧洲血统荷兰患者进行 HLA Ⅰ类和Ⅱ类基因分型，并与 5604 名荷兰健康献血者进行比较。
结果
在 MOG-IgG 阳性患者中未发现显著的 HLA 关联。AQP4-IgG 阳性患者 HLA-A01（61.9%比 33.7%，OR 3.16，95%CI，1.707-5.863，校正后[c] = 0.0045）、HLA-B08（61.9%比 25.6%，OR 4.66，95%CI，2.513-8.643，c < 0.0001）和 HLA-DRB1*03（51.2%比 27.6%，OR 2.75，95%CI，1.495-5.042，c = 0.0199）的频率显著更高。
结论
本研究表明 MOGAD 和 AQP4-IgG 阳性 NMOSD 的免疫遗传背景存在差异。与 HLA-A01、-B08 和 -DRB1*03 呈强烈正相关，提示该单倍型在具有欧洲血统的 AQP4-IgG 阳性 NMOSD 患者的病因中起作用，而在 MOGAD 中，这些疾病没有发现任何 HLA 相关性的证据。
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