{Reference Type}: Journal Article
{Title}: HLA-DR3 ~ DQ2 associates with sensory neuropathy in paraneoplastic neurological syndromes with Hu antibodies.
{Author}: Muñiz-Castrillo S;Villagrán-García M;Peris Sempere V;Farina A;Pinto AL;Picard G;Rogemond V;Honnorat J;Mignot E;
{Journal}: J Neurol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 11
{Factor}: 6.682
{DOI}: 10.1007/s00415-024-12534-7
{Abstract}: <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>Patients with anti-Hu PNS show different HLA profiles according to clinical presentation and, probably, cancer status, suggesting pathophysiological differences.