Rituximab impairs immunoglobulin (Ig)M and IgG (subclass) responses after influenza vaccination in rheumatoid arthritis patients
Rituximab impairs immunoglobulin (Ig)M and IgG (subclass) responses after influenza vaccination in rheumatoid arthritis patients
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DOI：
10.1111/cei.12390
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发表时间：
2014-10-01
影响因子：
4.6
通讯作者：
Bijl, M.
中科院分区：
文献类型：
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作者：
Westra, J.;van Assen, S.;Bijl, M.
利妥昔单抗（RTX）治疗类风湿性关节炎（RA）患者严重阻碍流感疫苗接种后的体液反应，如血凝抑制试验（HI）所确定的。尚不清楚HI是否反映免疫球蛋白（IG）M和IgG（亚类）流感应答，以及IgM抗体是否有助于RA患者中观察到的低流感感染率。甲氨蝶呤（MTX）的RA患者20人，RTX和28名健康对照（HC）接受三价流感亚单位疫苗接种23。在接种疫苗前和接种疫苗后28天，通过HI和IgM和IgG（亚类）酶联免疫吸附试验（ELISA）测定H1N1和H3 N2特异性抗体。接种前测定血清样本中的B细胞活化因子（BAFF）水平。免疫后HC组和MTX组的IgM和IgG（IgG 1和IgG 3）抗体均显著升高（P均< 0.01），RTX组则无明显变化。HI与IgG（IgG 1）呈显著相关，而与IgM无相关性。在RTX晚期患者（接种前6-10个月接受RTX治疗）中，对疫苗接种的IgG（IgG 1和IgG 3）应答恢复，但IgM应答未恢复。RA-RTX患者的BAFF水平显著升高，并与总IgG水平相关。血凝抑制试验用作金标准，主要检测IgG（IgG 1）反应。HC和RA患者接种疫苗后，IgM和IgG流感特异性抗体增加，接受RTX治疗的患者除外。BAFF水平在早期和晚期RTX治疗的患者中均升高，但与流感特异性抗体应答无关。
Rituximab (RTX) treatment in rheumatoid arthritis (RA) patients severely hampers humoral response after influenza vaccination as determined by haemagglutination inhibition assay (HI). It is not known whether HI reflects both immunoglobulin (Ig)M and IgG (subclass) influenza response, and whether IgM antibodies contribute to the low rate of influenza infection seen in RA patients. Twenty RA patients on methotrexate (MTX), 23 on RTX and 28 healthy controls (HC) received trivalent influenza subunit vaccination. Before and 28 days after vaccination, H1N1- and H3N2-specific antibodies were measured by HI and by IgM and IgG (subclass) enzyme-linked immunosorbent assay (ELISA). B cell activating factor (BAFF) levels were determined in serum samples before vaccination. Vaccination induced a significant increase of IgM and IgG (IgG1 and IgG3) antibodies against both strains in the HC and MTX groups (all P < 0.01), but not in the RTX group. HI correlated significantly in all cases with IgG (IgG1) but not with IgM. In RTX late patients (RTX treatment 6-10 months before vaccination), IgG (IgG1 and IgG3) response to vaccination was restored, but not IgM response. BAFF levels were significantly increased in RA-RTX patients and correlated with total IgG levels. Haemagglutination inhibition assay, used as gold standard, detects primarily IgG (IgG1) responses. IgM-and IgG influenza-specific antibodies increase after vaccination in HC and RA patients except in patients on RTX treatment. BAFF levels are increased in both early and late RTX-treated patients, but do not correlate with an influenza-specific antibody response.