Department of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands.
Ann Rheum Dis. 2013 Jun;72(6):1037-43. doi: 10.1136/annrheumdis-2011-201270. Epub 2012 Sep 11.
Experimental and human data suggest that tumour necrosis factor (TNF) blockade may affect B cell responses, in particular the induction of T cell-dependent (TD) humoral immunity. This study aimed to assess this hypothesis directly in patients with arthritis by analysing longitudinally the effect of TNF blockade on B cell activation and the maturation of humoral responses against TD and T cell-independent vaccines.
Peripheral blood samples were obtained from 56 spondyloarthritis patients before and after treatment with either non-steroidal anti-inflammatory drug (NSAID) alone or TNF blockers and analysed for B cell activation, plasma cell differentiation, germinal centre versus extra-follicular B cell maturation, and somatic hypermutation. Vaccine responses to hepatitis B and Streptococcus pneumoniae were measured by ELISA.
TNF blockade augmented B cell activation as reflected by the expression of early activation markers, CD40, and costimulatory molecules, without affecting differentiation towards plasmablasts. This was associated with a specific increase of the unswitched fraction of circulating memory B cells and a decreased level of somatic hypermutation in anti-TNF treated patients, indicating an impairment of the germinal centre-dependent B cell maturation. In agreement with these findings, TNF blockade profoundly suppressed the response to the TD vaccination against hepatitis B, whereas the T cell-independent response against pneumococcal polysaccharides was only modestly affected.
These data indicate that TNF blockade severely impedes the induction of primary TD humoral responses, probably by interfering with the germinal centre reaction.
实验和人体数据表明，肿瘤坏死因子（TNF）阻断可能会影响 B 细胞反应，特别是 T 细胞依赖性（TD）体液免疫的诱导。本研究旨在通过分析 TNF 阻断对关节炎患者 B 细胞激活和针对 TD 和 T 细胞非依赖性疫苗的体液反应成熟的长期影响，直接评估这一假设。
从 56 名脊柱关节炎患者中采集外周血样本，在单独使用非甾体抗炎药（NSAID）或 TNF 阻滞剂治疗前后进行分析，以评估 B 细胞激活、浆细胞分化、生发中心与滤泡外 B 细胞成熟以及体细胞超突变。通过 ELISA 测量乙型肝炎和肺炎球菌疫苗的反应。
TNF 阻断增强了 B 细胞的激活，表现为早期激活标志物 CD40 和共刺激分子的表达增加，而不影响向浆母细胞的分化。这与循环记忆 B 细胞未转换部分的特异性增加以及抗 TNF 治疗患者体细胞超突变水平降低有关，表明生发中心依赖性 B 细胞成熟受损。与这些发现一致，TNF 阻断严重抑制了针对乙型肝炎的 TD 疫苗接种的反应，而针对肺炎球菌多糖的 T 细胞非依赖性反应仅受到适度影响。
这些数据表明，TNF 阻断严重阻碍了原发性 TD 体液反应的诱导，可能是通过干扰生发中心反应。
