RESUMEN
Introducción. Los anticuerpos contra la aquaporina-4 (Ac-AQP-4) permitieron identificar como enfermedades diferentes a la neuromielitis óptica (NMO) y la esclerosis múltiple (EM). Estudios recientes sugieren que los alelos HLA-DRB1 contribuyen de forma diferente en la NMO y la EM en poblaciones no caucásicas. Nuestro objetivo fue analizar la distribución HLA-DRB1 en pacientes con NMO de origen caucásico. Sujetos y métodos. Se incluyó una cohorte de 22 pacientes con NMO (el 73% con Ac-AQP-4), 228 con EM y 225 controles sanos de origen español, y se genotipificó el locus HLA-DRB1. Posteriormente, los resultados se combinaron con los descritos en una población caucásica francesa: 45 pacientes con NMO (el 53% con Ac-AQP-4), 156 con EM y 310 controles sanos. Resultados. En la cohorte española, la NMO, en comparación con la EM, se asociaba a una mayor frecuencia del alelo DRB1*10 (odds ratio, OR = 15,1; intervalo de confianza del 95%, IC 95% = 3,26-69,84; p = 0,012). En el análisis combinado, y comparado con controles sanos, la NMO se asociaba a una mayor frecuencia del alelo DRB1*03 (OR = 2,27; IC 95% = 1,44-3,58; p < 0,0008), y esto se relacionaba con tener Ac-AQP-4 (OR = 2,74; IC 95% = 1,58-4,77; p < 0,0008). Por el contrario, la EM se asociaba a una mayor frecuencia del alelo DRB1*15 (OR = 2,09; IC 95% = 1,62-2,68; p < 0,0008) y a una menor frecuencia del alelo DRB1*07 (OR = 0,58; IC 95% = 0,44-0,78; p < 0,0008). Conclusiones. Los pacientes caucásicos con NMO y EM presentan una distribución alélica HLA-DRB1 diferente. El alelo DRB1*03 parece contribuir a ser IgG-NMO seropositivo. Son necesarios estudios multicéntricos colaborativos para conocer mejor la contribución genética en la susceptibilidad a padecer NMO (AU)
Introduction. The existence of antibodies to aquaporin-4 (AQP-4-ab) has identified neuromyelitis optica (NMO) and multiple sclerosis (MS) as different diseases. Although HLA-DRB1 alleles contribute to MS risk, recent studies suggest that HLA background differs between patients with NMO or MS in non-Caucasians populations. Our study was aimed to analyze HLA-DRB1 distribution in Caucasians NMO patients. Subjects and methods. We recruited a cohort of 22 NMO patients (73% were AQP-4-ab positive), 228 MS patients and 225 healthy controls from Spain and we genotyped the HLA-DRB1 locus. Then, we performed a pool analysis using reported data from 45 NMO patients (53% were AQP-4-ab positive), 156 MS patients and 310 healthy controls from Caucasian French population. Results. In the Spanish cohort, NMO was associated with increased frequency of DRB1*10 allele compared with MS (odds ratio, OR = 15.1; 95% confidence interval, 95% CI = 3.26-69.84; p = 0.012). In the pooled analysis, by comparison with healthy controls, NMO was associated with increased frequency of DRB1*03 allele (OR = 2.27; 95% CI = 1.44-3.58; p < 0.0008) which was related to AQP-4-ab seropositivity (OR = 2.74; 95% CI = 1.58-4.77; p < 0.0008). By contrast, MS as associated with increased frequency of DRB1*15 allele (OR = 2.09; 95% CI = 1.62-2.68; p < 0.0008) and decreased frequency of DRB1*07 allele (OR = 0.58; 95% CI = 0.44-0.78; p < 0.0008). Conclusions. Caucasian patients with NMO and MS have a different HLA-DRB1 allelic distribution. DRB1*03 allele seems to contribute to NMO seropositivity. Multicenter collaborative efforts are needed to adequately address the genetic contribution to NMO susceptibility (AU)