Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Neurology, Brain and Nerve Center, Fukuoka Central Hospital, 2-6-11 Yakuin, Chuo-ku, Fukuoka, 810-0022, Japan.
Sci Rep. 2021 Jan 12;11(1):607. doi: 10.1038/s41598-020-79833-7.
HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype-phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB104:05, DRB115:01 and DPB103:01 correlated with MS susceptibility and DRB101:01, DRB109:01, DRB113:02 and DPB104:01 were protective against MS. HLA-DRB115:01 was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. HLA-DRB104:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB103:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB101:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB109:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB113:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB108:02 and DPB105:01 were associated with susceptibility and DRB109:01 was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and HLA-DRB1*15:01 as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype-phenotype correlations are unclear in NMOSD.
HLA 基因型-临床表型相关性尚未在多发性硬化症 (MS) 和视神经脊髓炎谱系疾病 (NMOSD) 中建立。我们使用日本 MS/NMOSD 生物库材料研究了 528 例 MS 和 165 例 NMOSD 病例中的 HLA-DRB1/DPB1 基因型-表型相关性。HLA-DRB104:05、DRB115:01 和 DPB103:01 与 MS 易感性相关，而 DRB101:01、DRB109:01、DRB113:02 和 DPB104:01 则对 MS 具有保护作用。HLA-DRB115:01 与视神经炎和小脑受累增加以及视觉和锥体功能评分恶化相关，导致更高的进展指数值。HLA-DRB104:05 与发病年龄较早、视觉 FS 评分较高以及视神经炎发展倾向较高相关。HLA-DPB103:01 增加了脑干和小脑 FS 评分。相比之下，HLA-DRB101:01 降低了脊髓受累和感觉 FS 评分，HLA-DRB109:01 降低了年复发率、脑干受累和肠膀胱 FS 评分，而 HLA-DRB113:02 降低了脊髓和脑干受累。在 NMOSD 中，HLA-DRB108:02 和 DPB105:01 与易感性相关，而 DRB109:01 具有保护作用。多变量分析显示，在 MS 和 NMOSD 中，发病年龄较大、疾病持续时间较长和多次复发是独立的残疾风险因素，而 HLA-DRB1*15:01 仅在 MS 中是独立的风险因素。因此，易感和保护等位基因都可以影响 MS 的临床表现，而在 NMOSD 中，这种基因型-表型相关性尚不清楚。
