Cambridge Geraldine, Leandro Maria J, Edwards Jonathan C W, Ehrenstein Michael R, Salden Martin, Bodman-Smith Mark, Webster Anthony D B
Centre for Rheumatology, University College London, Arthur Stanley House, 40-50 Tottenham Street, London W1T 4NJ, UK.
Arthritis Rheum. 2003 Aug;48(8):2146-54. doi: 10.1002/art.11181.
To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion in 22 patients with rheumatoid arthritis (RA).
B lymphocyte depletion was attained using combination therapy based on the monoclonal anti-CD20 antibody rituximab. Levels of a serologic indicator of inflammation, C-reactive protein (CRP), of antimicrobial antibodies, of autoantibodies including IgA-, IgM-, and IgG-class rheumatoid factors (RF), and of antibodies to cyclic citrullinated peptide (anti-CCP) were assayed.
The majority of patients showed a marked clinical improvement after treatment with rituximab, with benefit lasting up to 33 months. Levels of total serum immunoglobulins fell, although the mean values each remained within the normal range. Whereas the IgM-RF response paralleled the changes in total serum IgM levels, the levels of IgA-RF, IgG-RF, and IgG and anti-CCP antibodies decreased significantly more than did those of their corresponding total serum immunoglobulin classes. The kinetics for the reduction in CRP levels also paralleled the decreases in autoantibody levels. In contrast, levels of antimicrobial antibodies did not change significantly. B lymphocyte return occurred up to 21 months posttreatment. The time to relapse after B lymphocyte return was often long and unpredictable (range 0-17 months). Relapse was, however, closely correlated with rises in the level of at least one autoantibody. Increased autoantibody levels were rarely observed in the absence of clinical change.
Following B lymphocyte depletion in patients with RA, a positive clinical response occurred in correlation with a significant drop in the levels of CRP and autoantibodies. Antibacterial antibody levels were relatively well maintained. B lymphocyte return preceded relapse in all patients. There was also a temporal relationship between clinical relapse and rises in autoantibody levels. Although these observations are consistent with a role for B lymphocytes in the pathogenesis of RA, the precise mechanisms involved remain unclear.
探讨22例类风湿关节炎（RA）患者B淋巴细胞清除后血清学变量及临床疾病活动度的变化。
采用基于单克隆抗CD20抗体利妥昔单抗的联合疗法实现B淋巴细胞清除。检测炎症血清学指标C反应蛋白（CRP）、抗菌抗体、包括IgA、IgM和IgG类类风湿因子（RF）在内的自身抗体以及环瓜氨酸肽抗体（抗CCP）的水平。
大多数患者在接受利妥昔单抗治疗后临床症状显著改善，疗效可持续长达33个月。血清总免疫球蛋白水平下降，尽管各平均值仍在正常范围内。IgM-RF反应与血清总IgM水平变化平行，而IgA-RF、IgG-RF、IgG及抗CCP抗体水平下降幅度明显大于相应的血清总免疫球蛋白类别。CRP水平降低的动力学也与自身抗体水平下降平行。相比之下，抗菌抗体水平无显著变化。治疗后长达21个月出现B淋巴细胞回潮。B淋巴细胞回潮后复发时间通常较长且不可预测（0 - 17个月）。然而，复发与至少一种自身抗体水平升高密切相关。在无临床变化的情况下很少观察到自身抗体水平升高。
RA患者B淋巴细胞清除后，临床出现阳性反应，同时CRP和自身抗体水平显著下降。抗菌抗体水平相对维持良好。所有患者复发前均出现B淋巴细胞回潮。临床复发与自身抗体水平升高之间也存在时间关系。尽管这些观察结果表明B淋巴细胞在RA发病机制中起作用，但具体机制仍不清楚。
