HLA-DR3 ~ DQ2 associates with sensory neuropathy in paraneoplastic neurological syndromes with Hu antibodies.
J Neurol
; 271(9): 6336-6342, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38990347
ABSTRACT
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*0501 (39% vs. 19%, OR = 2.8 [1.74-4.49]), DQB1*0201 (39% vs. 18%, OR = 2.88 [1.79-4.64]) and DRB1*0301 (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*0501 (OR = 3.12 [1.48-6.60]), DQB1*0201 (OR = 3.35 [1.57-7.15]) and DRB1*0301 (OR = 3.62 [1.64-7.97]); being even stronger in cases with sensory neuropathy, DQA1*0501 (OR = 4.41 [1.89-10.33]), DQB1*0201 (OR = 4.85 [2.04-11.53]) and DRB1*0301 (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.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Síndromes Paraneoplásicas do Sistema Nervoso
Limite:
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Neurol
Ano de publicação:
2024
Tipo de documento:
Article