Nived Per, Saxne Tore, Geborek Pierre, Mandl Thomas, Skattum Lillemor, Kapetanovic Meliha C
Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
2Department of Infectious Diseases, Central Hospital Kristianstad, J A Hedlunds väg 5, SE-291 85 Kristianstad, Sweden.
BMC Rheumatol. 2018 Apr 5;2:12. doi: 10.1186/s41927-018-0019-6. eCollection 2018.
Pneumococcal vaccination is recommended to patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). However, little is known whether the diseases influence pneumococcal vaccine response. This study aimed to investigate antibody response and functionality of antibodies following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in RA patients or pSS patients without disease modifying anti-rheumatic drugs (DMARD), compared to patients with RA treated with DMARD or to healthy controls.
Sixty RA patients (50 without DMARD and 10 with MTX), 15 patients with pSS and 49 controls received one dose of PCV13. Serotype-specific antibody concentrations for pneumococcal polysaccharides 6B and 23F and functionality of antibodies (23F) were determined in serum taken before and 4-6 weeks after vaccination using ELISA and opsonophagocytic activity assay (OPA), respectively. Proportions of individuals with positive antibody response (i.e. ≥ 2-fold increase from prevaccination concentrations; antibody response ratio; ARR ≥ 2), percentage of individuals reaching putative protective antibody level (i.e. ≥1.3 μg/mL) for both serotypes, and difference in OPA were calculated.
After vaccination, antibody concentrations for both serotypes increased in RA without DMARD ( < 0.001), pSS ( ≤ 0.05 and < 0.01) and controls ( < 0.001). Antibody responses to 6B and 23F were comparable in RA without DMARD (64% and 74%), pSS (67% and 53%) and controls (65% and 67%), but lower in the small group RA with MTX (both 20%, < 0.01). Similarly, significant increases of patients reaching protective antibody levels were seen in RA without DMARD ( ≤ 0.001) and controls ( < 0.001). After vaccination, OPA increased significantly in controls, RA and pSS without DMARD ( < 0.001 to 0.03), but not in RA with MTX.
Pneumococcal conjugate vaccine is immunogenic in RA and pSS patients without DMARD and in line with previous studies we support the recommendation that vaccination of RA patients should be performed before the initiation of MTX.
ClinicalTrials.gov Identifier: NCT02240888. Retrospectively registered 4 September, 2014.
推荐对类风湿关节炎（RA）患者和原发性干燥综合征（pSS）患者进行肺炎球菌疫苗接种。然而，对于这些疾病是否会影响肺炎球菌疫苗的反应知之甚少。本研究旨在调查与接受改善病情抗风湿药物（DMARD）治疗的RA患者或健康对照相比，未使用DMARD的RA患者或pSS患者接种13价肺炎球菌结合疫苗（PCV13）后的抗体反应及抗体功能。
60例RA患者（50例未使用DMARD，10例使用甲氨蝶呤[MTX]）、15例pSS患者和49例对照接受一剂PCV13。分别使用酶联免疫吸附测定（ELISA）和吞噬细胞杀菌活性测定（OPA），在接种疫苗前和接种后4 - 6周采集的血清中测定肺炎球菌多糖6B和23F的血清型特异性抗体浓度以及抗体（23F）的功能。计算抗体反应阳性个体的比例（即较接种前浓度增加≥2倍；抗体反应率；ARR≥2）、两种血清型均达到假定保护性抗体水平（即≥1.3μg/mL）的个体百分比以及OPA的差异。
接种疫苗后，未使用DMARD的RA患者（<0.001）、pSS患者（≤0.05和<0.01）和对照（<0.001）中两种血清型的抗体浓度均升高。未使用DMARD的RA患者（64%和74%）、pSS患者（67%和53%）和对照（65%和67%）对6B和23F的抗体反应相当，但使用MTX的RA患者小群体中反应较低（均为20%，<0.01）。同样，未使用DMARD的RA患者（≤0.001）和对照（<0.001）中达到保护性抗体水平的患者显著增加。接种疫苗后，对照、未使用DMARD的RA患者和pSS患者的OPA显著升高（<0.001至0.03），但使用MTX的RA患者中未升高。
肺炎球菌结合疫苗在未使用DMARD的RA患者和pSS患者中具有免疫原性，并且与先前的研究一致，我们支持RA患者应在开始使用MTX之前进行疫苗接种的建议。
ClinicalTrials.gov标识符：NCT02240888。2014年9月4日进行回顾性注册。
