Blanco Y, Ercilla-González G, Llufriu S, Casanova-Estruch B, Magraner M J, Ramió-Torrentá Ll, Mendibe-Bilbao M M, Uclés-Sánchez A J, Casado-Chocán J L, López de Munain A, Ramo-Tello C, Santos-Lasaosa S, Fernández-Bolaños Porras R, Segura-Bruna N, Sepulveda-Gázquez M, Villoslada P, Graus F, Saiz A
Servicio de Neurología, Hospital Clínicm, Barcelona, España.
Rev Neurol. 2011 Aug 1;53(3):146-52.
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 back-ground differs between patients with NMO or MS in non-Caucasians populations. Our study was aimed to analyze HLA-DRB1 distribution in Caucasians NMO patients.
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.
In the Spanish cohort, NMO was associated with increased frequency of DRB110 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 DRB103 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 was associated with increased frequency of DRB115 allele (OR = 2.09; 95% CI = 1.62-2.68; p < 0.0008) and decreased frequency of DRB107 allele (OR = 0.58; 95% CI = 0.44-0.78; p < 0.0008).
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.
水通道蛋白4抗体（AQP-4-ab）的存在已明确视神经脊髓炎（NMO）和多发性硬化症（MS）是不同的疾病。尽管HLA-DRB1等位基因会增加患MS的风险，但最近的研究表明，在非白种人群中，NMO或MS患者的HLA背景存在差异。我们的研究旨在分析白种人NMO患者中HLA-DRB1的分布情况。
我们从西班牙招募了一组22名NMO患者（73%为AQP-4-ab阳性）、228名MS患者和225名健康对照者，并对HLA-DRB1基因座进行基因分型。然后，我们使用来自法国白种人群的45名NMO患者（53%为AQP-4-ab阳性）、156名MS患者和310名健康对照者的报告数据进行汇总分析。
在西班牙队列中，与MS相比，NMO患者中DRB110等位基因的频率增加（优势比，OR = 15.1；95%置信区间，95%CI = 3.26 - 69.84；p = 0.012）。在汇总分析中，与健康对照相比，NMO与DRB103等位基因频率增加相关（OR = 2.27；95%CI = 1.44 - 3.58；p < 0.0008），这与AQP-4-ab血清阳性相关（OR = 2.74；95%CI = 1.58 - 4.77；p < 0.0008）。相比之下，MS与DRB115等位基因频率增加相关（OR = 2.09；95%CI = 1.62 - 2.68；p < 0.0008），而与DRB107等位基因频率降低相关（OR = 0.58；95%CI = 0.44 - 0.78；p < 0.0008）。
白种人NMO和MS患者具有不同的HLA-DRB1等位基因分布。DRB1*03等位基因似乎与NMO血清阳性有关。需要多中心合作努力，以充分解决基因对NMO易感性的影响。
