HLA-DR3 ~ DQ2 associates with sensory neuropathy in paraneoplastic neurological syndromes with Hu antibodies.

Autor: Muñiz-Castrillo S; Stanford Center for Sleep Sciences and Medicine, Stanford University, 3165 Porter Drive, Palo Alto, CA, 94304, USA., Villagrán-García M; French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Lyon, France.; MeLiS, UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France., Peris Sempere V; Stanford Center for Sleep Sciences and Medicine, Stanford University, 3165 Porter Drive, Palo Alto, CA, 94304, USA., Farina A; French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Lyon, France.; MeLiS, UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France., Pinto AL; French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Lyon, France.; MeLiS, UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France., Picard G; French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Lyon, France.; MeLiS, UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France., Rogemond V; French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Lyon, France.; MeLiS, UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France., Honnorat J; French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Lyon, France.; MeLiS, UCBL-CNRS UMR 5284, INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France., Mignot E; Stanford Center for Sleep Sciences and Medicine, Stanford University, 3165 Porter Drive, Palo Alto, CA, 94304, USA. mignot@stanford.edu.
Jazyk: angličtina
Zdroj: Journal of neurology [J Neurol] 2024 Sep; Vol. 271 (9), pp. 6336-6342. Date of Electronic Publication: 2024 Jul 11.
DOI: 10.1007/s00415-024-12534-7
Abstrakt: Objectives: 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.
Methods: 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.
Results: 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.
Discussion: Patients with anti-Hu PNS show different HLA profiles according to clinical presentation and, probably, cancer status, suggesting pathophysiological differences.
(© 2024. The Author(s).)
Databáze: MEDLINE
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