Anti-TNF treatment blocks the induction of T cell-dependent humoral responses
Anti-TNF treatment blocks the induction of T cell-dependent humoral responses
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DOI：
10.1136/annrheumdis-2011-201270
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发表时间：
2013-06-01
影响因子：
27.4
通讯作者：
Baeten, Dominique
中科院分区：
文献类型：
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作者：
Salinas, Gabriela Franco;De Rycke, Leen;Baeten, Dominique
目的实验和人体实验数据表明，阻断肿瘤坏死因子可影响B细胞应答，尤其是诱导T细胞依赖性(TD)体液免疫。这项研究旨在通过纵向分析肿瘤坏死因子阻断对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影响，直接在关节炎患者中评估这一假说。材料和方法采集56例脊柱炎患者单独使用非类固醇抗炎药(NSAID)或肿瘤坏死因子阻滞剂治疗前后的外周血样，分析B细胞激活、浆细胞分化、生发中心与毛囊外B细胞成熟和体细胞过度突变。结果阻断肿瘤坏死因子可增强B细胞的活化，表现为早期活化标志物CD40和共刺激分子的表达，但不影响其向浆母细胞的分化。这与接受抗肿瘤坏死因子治疗的患者循环记忆B细胞的非开关部分的特异性增加和体细胞超突变水平的降低有关，这表明生发中心依赖的B细胞成熟受到损害。与此结果一致，阻断肿瘤坏死因子能显著抑制TD疫苗对乙肝疫苗的免疫应答，而对肺炎球菌多糖的T细胞非依赖性免疫应答仅有轻微影响。结论这些数据表明，阻断肿瘤坏死因子能严重抑制TD的原发体液免疫应答，可能是通过干扰生发中心反应。
Objective 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.Materials and methods 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.Results 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.Conclusions These data indicate that TNF blockade severely impedes the induction of primary TD humoral responses, probably by interfering with the germinal centre reaction.