Albani S, Ravelli A, Massa M, De Benedetti F, Andree G, Roudier J, Martini A, Carson D A
Department of Medicine, University of California, San Diego 92093-0663.
J Pediatr. 1994 Apr;124(4):561-5. doi: 10.1016/s0022-3476(05)83134-8.
Patients with juvenile rheumatoid arthritis frequently have abnormal immune responses to the hsp65 class of bacterial heat shock proteins. However, lymphocytes from children with other inflammatory diseases may also recognize hsp65, and the role of these antigens in juvenile rheumatoid arthritis remains controversial. We have studied humoral and cellular immune responses to a distinct, recently described bacterial heat shock protein, designated dnaJ. The Escherichia coli dnaJ gene was cloned and expressed, and the purified recombinant protein was used as an antigen. Neither normal children nor children with various chronic inflammatory diseases had lymphocyte proliferative responses to recombinant dnaJ. However, lymphocytes from patients with polyarticular, pauciarticular, and systemic manifestations of juvenile rheumatoid arthritis responded strongly to the antigen. Cellular immune responses to dnaJ were higher in synovial fluid than in blood and higher in children with active disease than in children in remission. These data show that increased immune reactivity to dnaJ is characteristic of juvenile rheumatoid arthritis and that the magnitude of the immune response is linked to disease activity. The results suggest that an abnormal immune response to antigens on commensal gut bacteria may contribute to the generation of chronic inflammation in juvenile rheumatoid arthritis.
青少年类风湿性关节炎患者对细菌热休克蛋白hsp65类常常有异常的免疫反应。然而,患有其他炎症性疾病的儿童的淋巴细胞也可能识别hsp65,并且这些抗原在青少年类风湿性关节炎中的作用仍存在争议。我们研究了对一种独特的、最近描述的细菌热休克蛋白(称为dnaJ)的体液免疫和细胞免疫反应。克隆并表达了大肠杆菌dnaJ基因,纯化的重组蛋白用作抗原。正常儿童和患有各种慢性炎症性疾病的儿童对重组dnaJ均无淋巴细胞增殖反应。然而,患有青少年类风湿性关节炎多关节、少关节和全身表现的患者的淋巴细胞对抗原有强烈反应。对dnaJ的细胞免疫反应在滑液中高于血液,在患有活动性疾病的儿童中高于缓解期儿童。这些数据表明,对dnaJ的免疫反应性增加是青少年类风湿性关节炎的特征,并且免疫反应的程度与疾病活动相关。结果表明,对共生肠道细菌上的抗原的异常免疫反应可能有助于青少年类风湿性关节炎中慢性炎症的产生。