Cambridge Geraldine, Stohl William, Leandro Maria J, Migone Thi-Sau, Hilbert David M, Edwards Jonathan C W
University College London, London, UK.
Arthritis Rheum. 2006 Mar;54(3):723-32. doi: 10.1002/art.21650.
To assess the effects of B lymphocyte depletion on serum B lymphocyte stimulator (BLyS; trademark of Human Genome Sciences, Rockville, MD) levels in patients with rheumatoid arthritis (RA), and to assess the relationship of serum BLyS levels with peripheral blood B cell depletion, levels of autoantibodies and antimicrobial antibodies, the return of peripheral blood B cells, and clinical relapse.
Fifteen patients with active RA underwent rituximab-based B cell depletion therapy (BCDT). Disease activity was assessed clinically, peripheral blood CD19+ B cell counts were determined by flow cytometry, and serum levels of BLyS, IgM, IgA, and IgG rheumatoid factors (RFs), anti-cyclic citrullinated peptide, and antimicrobial antibodies were assessed using enzyme-linked immunosorbent assays.
Peripheral blood B cell depletion was achieved in all 15 patients, and an American College of Rheumatology 20% response was achieved in 13 patients. Following clinical relapse, 7 patients underwent at least 1 additional cycle of BCDT. In every case, serum BLyS levels markedly rose post-BCDT and remained elevated for at least 1-2 months. Serum levels of RF, but not those of anti-tetanus toxoid or anti-pneumococcal polysaccharide antibodies, fell significantly. A decline in serum BLyS levels was associated with the reemergence of B cells in peripheral blood, which, in turn, antedated clinical relapse by variable periods of time. The patterns of B cell depletion, serum BLyS and antibody levels, and clinical relapse for each BCDT cycle were remarkably similar in re-treated patients.
Rituximab-based BCDT leads to marked increases in serum BLyS levels. This may contribute significantly to the survival and/or regeneration of B cell populations capable of triggering clinical relapse.
评估B淋巴细胞清除对类风湿关节炎（RA）患者血清B淋巴细胞刺激因子（BLyS；人类基因组科学公司商标，罗克维尔，马里兰州）水平的影响，并评估血清BLyS水平与外周血B细胞清除、自身抗体和抗微生物抗体水平、外周血B细胞恢复以及临床复发之间的关系。
15例活动期RA患者接受了基于利妥昔单抗的B细胞清除疗法（BCDT）。通过临床评估疾病活动度，采用流式细胞术测定外周血CD19+B细胞计数，并使用酶联免疫吸附测定法评估血清BLyS、IgM、IgA和IgG类风湿因子（RFs）、抗环瓜氨酸肽抗体以及抗微生物抗体水平。
所有15例患者均实现外周血B细胞清除，13例患者达到美国风湿病学会20%反应标准。临床复发后，7例患者至少接受了1个额外周期的BCDT。在每种情况下，血清BLyS水平在BCDT后均显著升高，并至少持续升高1 - 2个月。RF血清水平显著下降，但抗破伤风类毒素或抗肺炎球菌多糖抗体水平未下降。血清BLyS水平下降与外周血B细胞重新出现相关，而外周血B细胞重新出现又早于临床复发不同时间。在再次接受治疗的患者中，每个BCDT周期的B细胞清除模式、血清BLyS和抗体水平以及临床复发情况非常相似。
基于利妥昔单抗的BCDT导致血清BLyS水平显著升高。这可能对能够引发临床复发的B细胞群体的存活和/或再生有显著贡献。
