目的 研究人类白细胞抗原 (HLA) 和副肿瘤性神经综合征 (PNS) 与 Hu 抗体之间的关联，以及根据临床表现和癌症状态的潜在特异性。四位数分辨率的 HLA 基因型是根据可用的全基因组关联数据估算的。使用由三个主要成分控制的逻辑回归，比较患者（整个队列，n = 100，并根据临床表现和癌症状态）和匹配的健康对照（n = 508）之间的等位基因携带频率。100个抗的临床表现-Hu 患者累及中枢神经系统（28 例，28%）、周围神经系统（36 例，36%）或两者结合（36 例，36%）。 75 人 (75%) 被确诊为癌症。 HLA关联分析显示，抗Hu PNS患者更频繁地携带DQA1*05:01（39% vs. 19%，OR = 2.8 [1.74-4.49]）、DQB1*02:01（39% vs. 18%） ，OR = 2.88 [1.79-4.64]）和 DRB1*03:01（41% vs. 19%，OR = 2.92 [1.80-4.73]）高于健康对照。值得注意的是，这种 DR3 ~ DQ2 关联在纯粹中枢受累的患者中不存在，但对于那些表现为外周受累的患者更具体：DQA1*05:01 (OR = 3.12 [1.48-6.60])、DQB1*02:01 (OR = 3.35[1.57-7.15]）和DRB1*03:01（OR = 3.62[1.64-7.97]）；在感觉神经病变的情况下，DQA1*05:01 (OR = 4.41 [1.89-10.33])、DQB1*02:01 (OR = 4.85 [2.04-11.53]) 和 DRB1*03:01 (OR = 5.79) 甚至更强[2.28-14.74]）。同样，DR3 ~ DQ2 关联仅在癌症患者中观察到。抗 Hu PNS 患者根据临床表现和可能的癌症状态显示出不同的 HLA 谱，表明病理生理学差异。© 2024。作者。

To investigate the association between human leukocyte antigen (HLA) and paraneoplastic neurological syndromes (PNS) with Hu antibodies, and potential specificities according to clinical presentation and cancer status.HLA genotypes at four-digit resolution were imputed from available genome-wide association data. Allele carrier frequencies were compared between patients (whole cohort, n = 100, and according to clinical presentation and cancer status) and matched healthy controls (n = 508) using logistic regression controlled by the three main principal components.The clinical presentation of 100 anti-Hu patients involved the central nervous system (28, 28%), the peripheral nervous system (36, 36%) or both combined (36, 36%). Cancer diagnosis was certain in 75 (75%). HLA association analyses revealed that anti-Hu PNS patients were more frequently carriers of DQA1*05:01 (39% vs. 19%, OR = 2.8 [1.74-4.49]), DQB1*02:01 (39% vs. 18%, OR = 2.88 [1.79-4.64]) and DRB1*03:01 (41% vs. 19%, OR = 2.92 [1.80-4.73]) than healthy controls. Remarkably, such DR3 ~ DQ2 association was absent in patients with pure central involvement, but more specific to those manifesting with peripheral involvement: DQA1*05:01 (OR = 3.12 [1.48-6.60]), DQB1*02:01 (OR = 3.35 [1.57-7.15]) and DRB1*03:01 (OR = 3.62 [1.64-7.97]); being even stronger in cases with sensory neuropathy, DQA1*05:01 (OR = 4.41 [1.89-10.33]), DQB1*02:01 (OR = 4.85 [2.04-11.53]) and DRB1*03:01 (OR = 5.79 [2.28-14.74]). Similarly, DR3 ~ DQ2 association was only observed in patients with cancer.Patients with anti-Hu PNS show different HLA profiles according to clinical presentation and, probably, cancer status, suggesting pathophysiological differences.© 2024. The Author(s).