Kapetanovic Meliha C, Nagel Johanna, Nordström Inger, Saxne Tore, Geborek Pierre, Rudin Anna
Department of Clinical Sciences, Skåne University Hospital, Lund, Section for Rheumatology, Sweden.
Department of Rheumatology & Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Vaccine. 2017 Feb 7;35(6):903-908. doi: 10.1016/j.vaccine.2016.12.068. Epub 2017 Jan 9.
Treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA) leads to decreased total immunoglobulin (Ig) levels and impairs vaccine-specific IgG antibody levels following pneumococcal vaccination. The mechanisms by which MTX exerts these effects in RA are unknown. We aimed to evaluate whether MTX reduces vaccine-specific serum Ig levels and their functionality in RA patients following vaccination with pneumococcal conjugate vaccine, and if numbers of antigen-specific circulating plasmablasts are affected.
Ten patients with RA on MTX and 10 RA patients without disease modifying anti-rheumatic drug (DMARD) were immunized with a dose 13-valent pneumococcal conjugate vaccine (Prevenar13). Circulating plasmablasts producing total IgG and IgA as well as specific IgG and IgA against two pneumococcal capsular serotypes (6B and 23F) were enumerated using ELISPOT 6days after vaccination. IgG levels against both these serotypes were determined with ELISA before and 4-6weeks after vaccination. Positive antibody response was defined as ⩾2-fold increase of pre-vaccination antibody levels. The functionality of vaccine specific antibodies to serotype 23F was evaluated by measuring their ability to opsonize bacteria using opsonophagocytic assay (OPA) in 4 randomly chosen RA patients on MTX and 4 RA patients without DMARD.
After vaccination, RA patients on MTX showed significant increase in pre- to postvaccination antibody levels for 6B (p<0.05), while patients without DMARD had significant increases for both 6B and 23F (p<0.05 and p<0.01, respectively). Only 10% of RA on MTX and 40% of RA patients without DMARD showed positive post-vaccination antibody responses for both serotypes. Increased opsonizing ability after vaccination was detected in 1 of 4 RA patients on MTX and 3 of 4 patients on RA without DMARD. However, numbers of circulating total and vaccine-specific IgG- or IgA-producing plasmablasts did not differ between RA patients with or without MTX.
MTX treatment in RA leads to reduced vaccine-specific antibody responses and their functionality compared to untreated RA following pneumococcal vaccination using polysaccharide-protein conjugate vaccine. However, since there was no reduction in numbers of circulating total or vaccine-specific antibody-producing plasmablasts after vaccination this effect is probably not due to reduced activation of B cells in lymphoid tissue.
NCT02240888.
类风湿关节炎（RA）患者使用甲氨蝶呤（MTX）治疗会导致总免疫球蛋白（Ig）水平降低，并损害肺炎球菌疫苗接种后疫苗特异性IgG抗体水平。MTX在RA中产生这些作用的机制尚不清楚。我们旨在评估MTX是否会降低RA患者接种肺炎球菌结合疫苗后疫苗特异性血清Ig水平及其功能，以及抗原特异性循环浆母细胞数量是否受到影响。
10例接受MTX治疗的RA患者和10例未使用改善病情抗风湿药物（DMARD）的RA患者接种一剂13价肺炎球菌结合疫苗（沛儿13）。接种疫苗6天后，使用ELISPOT法计数产生总IgG和IgA以及针对两种肺炎球菌荚膜血清型（6B和23F）的特异性IgG和IgA的循环浆母细胞。在接种疫苗前和接种后4 - 6周用ELISA法测定针对这两种血清型的IgG水平。阳性抗体反应定义为接种前抗体水平增加⩾2倍。在4例随机选择的接受MTX治疗的RA患者和4例未使用DMARD的RA患者中，通过调理吞噬试验（OPA）测量疫苗特异性抗体对23F血清型调理细菌的能力，评估其功能。
接种疫苗后，接受MTX治疗的RA患者6B血清型接种前后抗体水平显著升高（p<0.05），而未使用DMARD的患者6B和23F血清型抗体水平均显著升高（分别为p<0.05和p<0.01）。接受MTX治疗的RA患者中只有10%，未使用DMARD的RA患者中有40%两种血清型接种后抗体反应呈阳性。接受MTX治疗的4例RA患者中有1例，未使用DMARD的4例RA患者中有3例接种后检测到调理能力增强。然而，接受或未接受MTX治疗的RA患者之间，循环中产生总抗体和疫苗特异性IgG或IgA的浆母细胞数量没有差异。
与未接受治疗的RA患者接种多糖 - 蛋白结合疫苗的肺炎球菌疫苗后相比，RA患者接受MTX治疗会导致疫苗特异性抗体反应及其功能降低。然而，由于接种疫苗后循环中产生总抗体或疫苗特异性抗体的浆母细胞数量没有减少，这种效应可能不是由于淋巴组织中B细胞活化减少所致。
NCT02240888。
