Van Jaarsveld C H, Otten H G, Jacobs J W, Kruize A A, Brus H L, Bijlsma J W
Rheumatic Research Foundation Utrecht, Department of Rheumatology and Clinical Immunology, University Hospital Utrecht, The Netherlands.
Br J Rheumatol. 1998 Apr;37(4):411-6. doi: 10.1093/rheumatology/37.4.411.
The clinical expression of rheumatoid arthritis (RA) varies considerably among individual patients. Genetic variations in human leucocyte antigen (HLA) may influence clinical expression. We re-examined the association of HLA-DR with susceptibility to and clinical expression of RA using genomic tissue typing, since most studies were based on (less reliable) serological techniques. Seventy-eight patients with recent-onset RA, all participating in a clinical trial on therapeutic strategies, were HLA-DR typed by means of low-resolution genomic typing. Cumulative disease activity within the first 3 yr of disease was measured. Of the RA patients, 54% expressed DR4 (DR4+) vs 26% of healthy controls. Rheumatoid factor (RF)-positive patients had a higher cumulative disease activity than RF-negative patients. Patients who were either DR1+ or DR4+ had a higher cumulative disease activity than those who expressed neither DR1 nor DR4. This association was less obvious after correction for RF status. The association of DR52+ (DR3, 5, 6) and a lower cumulative disease activity could also not be demonstrated after correction for RF status. Among RF-negative patients, DR51+ (or DR2+) was associated with a higher cumulative disease activity. Other HLA-DR types (including DR1 and DR4 separately) were not associated with the severity of RA. DR4 was associated with susceptibility to RA in our patients; HLA-DR low-resolution genomic tissue typing did not yield additional information to RF status for the clinical identification of individual patients with a poor prognosis.
类风湿关节炎（RA）的临床表现因个体患者而异。人类白细胞抗原（HLA）的基因变异可能会影响临床表现。由于大多数研究基于（可靠性较低的）血清学技术，我们使用基因组组织分型重新审视了HLA - DR与RA易感性及临床表现之间的关联。78例近期发病的RA患者均参与了一项治疗策略临床试验，通过低分辨率基因组分型对其进行HLA - DR分型。测量了疾病最初3年内的累积疾病活动度。在RA患者中，54%表达DR4（DR4 +），而健康对照者中这一比例为26%。类风湿因子（RF）阳性患者的累积疾病活动度高于RF阴性患者。DR1 +或DR4 +的患者比既不表达DR1也不表达DR4的患者累积疾病活动度更高。校正RF状态后，这种关联不太明显。校正RF状态后，也未证实DR52 +（DR3、5、6）与较低的累积疾病活动度之间存在关联。在RF阴性患者中，DR51 +（或DR2 +）与较高的累积疾病活动度相关。其他HLA - DR类型（包括单独的DR1和DR4）与RA的严重程度无关。在我们的患者中，DR4与RA易感性相关；HLA - DR低分辨率基因组组织分型对于临床识别预后不良的个体患者，并未提供超出RF状态的额外信息。
