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Influence of histocompatibility genes on disease susceptibility and treatment response in patients with relapsing-remitting multiple sclerosis treated with interferon β-1a

机译:组织相容性基因对干扰素β-1a治疗复发缓解型多发性硬化患者疾病易感性和治疗反应的影响

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摘要

Multiple sclerosis (MS) is the most common, non-traumatic cause of neurological disability in young adults. The aim of this study was to investigate the influence of HLA class II alleles DRB1* and DQB1* on susceptibility to relapsing-remitting (RR) MS and response to interferon (IFN) β-1a treatment. A prospective observational study was conducted. Seventeen patients with clinically definite RRMS, attending a tertiary referral center for multiple sclerosis in Israel and receiving treatment with subcutaneous IFN β-1a, 22 mcg three times weekly were recruited between December 1998 and February 2000 and observed for 12 months. HLA genotyping was performed and clinical characteristics (relapse rate and disability progression) assessed at baseline and after 12 months. HLA data for a healthy control group were also used for comparison. HLA and the success of treatment with IFN β-1a in this group of RRMS patients were assessed. The frequency of DRB1*03 was six times higher in patients treated with IFN β-1a than in the healthy control group (n=100): 29% (5/17) versus 5% (5/100), respectively. Additionally, DQB1*03 and DQB1*02 were present in 82% (14/17) and 41% (7/17) of RRMS patients, but in only 33% (33/100) and 18% (18/100) of control patients, respectively. A better response to IFN β-1a treatment was seen in patients carrying these alleles than in patients without these alleles. Our results indicated that DRB1*03, DQB1*03 and DQB1*02 alleles may contribute to MS susceptibility and IFN β-1a responsiveness, and warrant further verification in a larger population.
机译:多发性硬化症(MS)是年轻人中神经功能障碍的最常见,非创伤性原因。这项研究的目的是调查HLA II类等位基因DRB1 *和DQB1 *对复发-缓解(RR)MS的易感性以及对干扰素(IFN)β-1a治疗的反应的影响。进行了一项前瞻性观察研究。 1998年12月至2000年2月,共招募了17名临床上确定的RRMS患者,他们在以色列的多发性硬化三级转诊中心就诊,每周3次接受皮下IFNβ-1a(22 mcg)治疗,每周三次,观察12个月。在基线和12个月后进行HLA基因分型,并评估临床特征(复发率和残疾进展)。健康对照组的HLA数据也用于比较。评估了这组RRMS患者的HLA和IFNβ-1a治疗的成功率。用IFNβ-1a治疗的患者DRB1 * 03的频率是健康对照组(n = 100)的六倍:分别为29%(5/17)和5%(5/100)。此外,DRMSB1 * 03和DQB1 * 02存在于RRMS患者的82%(14/17)和41%(7/17)中,但仅在33%(33/100)和18%(18/100)的RRMS患者中存在分别控制患者。携带这些等位基因的患者比没有携带这些等位基因的患者对IFNβ-1a治疗的反应更好。我们的结果表明,DRB1 * 03,DQB1 * 03和DQB1 * 02等位基因可能对MS易感性和IFNβ-1a反应性有贡献,并需要在更大的人群中进一步验证。

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