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类风湿关节炎患者诊断时及使用改善病情抗风湿药物治疗后的外周血B细胞亚群变化:与临床和实验室参数的相关性

Changes in peripheral blood B cell subsets at diagnosis and after treatment with disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: correlation with clinical and laboratory parameters.

作者信息

McComish Jeremy, Mundy Joy, Sullivan Tom, Proudman Susanna M, Hissaria Pravin

机构信息

Division of Human Immunology, SA Pathology (IMVS), Adelaide, South Australia, Australia.

Immunology and Allergy Unit, Flinders Medical Centre, Bedford Park, Adelaide, South Australia, Australia.

出版信息

Int J Rheum Dis. 2015 May;18(4):421-32. doi: 10.1111/1756-185X.12325. Epub 2014 Mar 2.

DOI:10.1111/1756-185X.12325
PMID:24589014
Abstract

OBJECTIVE

To assess variation in peripheral blood B lymphocyte subsets in rheumatoid arthritis (RA).

METHODS

B lymphocyte subsets in disease-modifying anti-rheumatic drug (DMARD)-naïve patients with RA (n = 30), patients with RA treated with DMARDs (n = 73) and healthy controls (n = 46) were analyzed by flow cytometry. Total B cells, total memory B cells, immunoglobulin M (IgM) memory B cells, switched memory B cells, non-switched memory B cells, CD21lo B cells, transitional B cells and plasmablasts were measured. Correlation with clinical and laboratory parameters was performed.

RESULTS

Total memory B cells, IgM memory B cells and non-switched memory B cells were reduced in RA patients at diagnosis compared to controls (P < 0.05). In patients with treated RA, there was a further reduction of total B cells, CD21lo cells, transitional B cells and plasmablasts, compared to controls (P < 0.05). The reduction in absolute numbers of total B cells, switched memory B cells, CD21lo cells, transitional B cells and plasmablasts in treated RA patients was significant (P < 0.05) even when compared to the DMARD-naïve patients. Only treatment responders (Disease Activity Score < 3.2) had reduced total B cells and absolute numbers of switched and IgM memory B cells (P < 0.05). In patients requiring leflunomide, total memory B cells, IgM memory B cells, non-switched memory B cells and absolute numbers of switched memory B cells were reduced compared with the remainder of the patient group (P < 0.05).

CONCLUSION

There is reduction of various B cell subsets in RA patients at diagnosis. Treatment with DMARDs leads to further reduction in additional B cell subsets without correction of the abnormalities. Reduction in individual subsets may predict RA patients requiring more intensive therapy.

摘要

目的

评估类风湿关节炎(RA)患者外周血B淋巴细胞亚群的变化。

方法

采用流式细胞术分析初治抗风湿药物(DMARD)的RA患者(n = 30)、接受DMARDs治疗的RA患者(n = 73)和健康对照者(n = 46)的B淋巴细胞亚群。检测总B细胞、总记忆B细胞、免疫球蛋白M(IgM)记忆B细胞、转换型记忆B细胞、未转换型记忆B细胞、CD21lo B细胞、过渡性B细胞和成浆细胞。分析其与临床和实验室参数的相关性。

结果

与对照组相比,RA患者诊断时总记忆B细胞、IgM记忆B细胞和未转换型记忆B细胞减少(P < 0.05)。与对照组相比,接受治疗的RA患者总B细胞、CD21lo细胞、过渡性B细胞和成浆细胞进一步减少(P < 0.05)。即使与初治患者相比,接受治疗的RA患者总B细胞、转换型记忆B细胞、CD21lo细胞、过渡性B细胞和成浆细胞的绝对数量减少也有统计学意义(P < 0.05)。只有治疗反应者(疾病活动评分< 3.2)总B细胞以及转换型和IgM记忆B细胞的绝对数量减少(P < 0.05)。与其余患者组相比,需要来氟米特治疗的患者总记忆B细胞、IgM记忆B细胞、未转换型记忆B细胞以及转换型记忆B细胞的绝对数量减少(P < 0.05)。

结论

RA患者诊断时多种B细胞亚群减少。DMARDs治疗导致更多B细胞亚群进一步减少,异常未得到纠正。个别亚群的减少可能预示RA患者需要更强化的治疗。

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