类风湿关节炎患者外周血与滑膜液Ⅰ、Ⅱ、Ⅸ、Ⅹ、Ⅺ型胶原反应性B细胞频率的比较

Frequencies of autoreactive B cells toⅠ,Ⅱ,Ⅸ,Ⅹ and Ⅺ collagens in patients with rheumatoid arthritis

目的 探讨抗不同类型胶原B细胞反应在类风湿关节炎(RA)出现的意义。方法 以EL4OUrBUr/rIL2/PMA作为刺激系统,应用酶联斑点技术,检测抗Ⅰ、Ⅱ、Ⅸ、Ⅹ、Ⅺ型胶原免疫球蛋白分泌细胞(antiHCⅡISC)。结果 28例RA患者外周血及滑膜液中21例出现antiHCⅡISC,Ⅰ、Ⅸ、Ⅹ、Ⅺ型胶原反应性B细胞阳性者分别为5、6、11及9例。虽然对某种胶原的反应水平与抗其它型胶原反应水平并不一致,但抗Ⅰ、Ⅸ、Ⅹ、Ⅺ型胶原反应多与Ⅱ型胶原反应同时存在。结论 Ⅰ、Ⅱ、Ⅸ、Ⅹ、Ⅺ型胶原特异性B细胞均参与RA的免疫病理反应。

Objective To analyse the frequencies of B cell reactions to collagen types Ⅰ、Ⅱ、Ⅸ、Ⅹ and Ⅺ in patients with rheumatoid arthritis (RA) and osteoathritis (OA). Methods Peripheral blood mononuclear cells (PBMC) and the corresponding synovial fluid mononuclear cells (SFMC) of 28 patients and 15 OA controls were quantified for anti HC Ⅰ,Ⅱ,Ⅸ,Ⅹand Ⅺ immunoglobulin (Ig) secreting cells (ISC) with enzyme linked immunospot assay (ELISPOT) after stimulation with the EL 4 thymoma cell line (clone OU r BU r), recombinant human IL 2 and PMA. Results Anti HC Ⅱ B cell response was most frequent, it was present in 21 RA patients. Autoreactive B cells to collagen typesⅠ,Ⅸ, and Ⅺ were observed less frequently, and found only in 5,6 and 9 RA patients, respectively. The B cell response specific for collagen Ⅹ which is only synthesized by hypertrophic chondrocytes was present in the synovial fluids of 11 RA patients. Although changes in the levels of B cell response to one collagen type were not necessarily linked to changes in the levels of B cell response to other collages, anti HC Ⅰ,Ⅸ,Ⅹand Ⅺ B cell reactions nearly always occurred together with the presence of anti HC ⅡB cell reaction. No correlation was found between collagen specific B cell response and clinic features. Conclusions B cell responses to different collagen molecules, as a result of different antigenic epitopes being exposed by cartilage degradation at different times throughout the disease, might be associated with the degrees of cartilage destruction or the different stages of disease progression. However, anti collagen Ⅹ immune response is not simply represent epiphenomena resulted from cartilage destruction, like the RA group, all patients of OA control group have undergone joint surgery due to severe cartilage destruction.