Rau R, Herborn G, Zueger S, Fenner H
Department of Rheumatology, Evangelisches Fachkrankenhaus Ratingen, Germany.
J Rheumatol. 2000 Nov;27(11):2566-75.
To investigate the relationship between radiographic disease progression in the presence or absence of rheumatoid arthritis (RA) linked HLA-DRB1 alleles after early introduction of disease modifying antirheumatic drug therapy in patients with RA over a study period of 6 years.
One hundred nine patients of a trial comparing intramuscular (im) gold sodium thiomalate (GSTM) and im methotrexate (MTX) in early erosive RA were followed for 6 years with regular assessments of clinical and laboratory data and yearly radiographs of hands and feet, and they were typed for HLA-DRB1 genes. Radiographic progression was analyzed for an influence of rheumatoid factor (RF) status and HLA-DRB1 genes.
Twenty-seven patients (25%) were positive for two, 46 (42%) for one, and 36 (33%) for none of the disease linked alleles. A decrease of the rate of radiographic disease progression with treatment in this group of patients was reflected by the decline in the slope of the radiographic score. Seropositive patients (n = 71, 68%) had a significantly more destructive disease course than RF negative patients. In seropositive disease, patients with a "double dose" of RA linked alleles showed a tendency to greater progression during the first 12-24 mo of treatment, but no significant difference in the longterm radiographic outcome could be detected between subgroups defined by the presence or absence of HLA-DRB1 genes. There was no significant difference throughout the study period with respect to the clinical disease course as assessed by joint swelling, C-reactive protein, and erythrocyte sedimentation rate. The majority of the seronegative population (n = 38, 32%) had a benign disease course with the exception of patients (n = 6) with the double allele; they had radiographic disease progression comparable with the seropositive patients.
Our data do not provide evidence for a more aggressive disease course in patients bearing double RA linked HLA-DRB1 alleles.
在一项为期6年的研究中，调查类风湿关节炎（RA）患者在早期引入改善病情抗风湿药物治疗后，存在或不存在与RA相关的HLA - DRB1等位基因时，影像学疾病进展之间的关系。
一项比较肌肉注射硫代苹果酸金钠（GSTM）和肌肉注射甲氨蝶呤（MTX）治疗早期侵蚀性RA的试验中的109例患者，接受了为期6年的随访，定期评估临床和实验室数据，并每年拍摄手足X线片，同时对他们进行HLA - DRB1基因分型。分析类风湿因子（RF）状态和HLA - DRB1基因对影像学进展的影响。
27例患者（25%）携带两个与疾病相关的等位基因呈阳性，46例（42%）携带一个呈阳性，36例（33%）携带零个呈阳性。该组患者治疗后影像学疾病进展速率的降低通过影像学评分斜率的下降得以体现。血清阳性患者（n = 71，68%）的疾病进程比RF阴性患者更具破坏性。在血清阳性疾病中，携带“双倍剂量”RA相关等位基因的患者在治疗的前12 - 24个月有进展更快的趋势，但根据是否存在HLA - DRB1基因定义的亚组之间，长期影像学结果未发现显著差异。在整个研究期间，通过关节肿胀、C反应蛋白和红细胞沉降率评估的临床疾病进程没有显著差异。大多数血清阴性人群（n = 38，32%）的疾病进程较为良性，但携带双等位基因的患者（n = 6）除外；他们的影像学疾病进展与血清阳性患者相当。
我们的数据没有提供证据表明携带两个与RA相关的HLA - DRB1等位基因的患者疾病进程更具侵袭性。
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