接受标准治疗的系统性血管炎患者对肺炎球菌结合疫苗的免疫反应。
Immune response to pneumococcal conjugate vaccine in patients with systemic vasculitis receiving standard of care therapy.
作者信息
Nived Per, Nagel Johanna, Saxne Tore, Geborek Pierre, Jönsson Göran, Skattum Lillemor, Kapetanovic Meliha C
机构信息
Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden; Department of Infectious Diseases, Central Hospital Kristianstad, J A Hedlunds väg 5, SE-291 85 Kristianstad, Sweden.
Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
出版信息
Vaccine. 2017 Jun 22;35(29):3639-3646. doi: 10.1016/j.vaccine.2017.05.044. Epub 2017 May 25.
AIM
To study the effect of standard of care therapy on antibody response and functionality following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in patients with primary systemic vasculitis compared to healthy controls.
METHODS
49 patients with vasculitis and 49 controls received a single dose (0.5ml) PCV13 intramuscularly. Ongoing treatments: azathioprine (AZA; n=11), cyclophosphamide (CYC; n=6), methotrexate (MTX; n=9), rituximab (n=3); anti-TNF (n=2), mycophenolate mofetil (n=2), prednisolone alone (n=15) and no active treatment (n=2). Specific antibody concentrations for serotypes 6B and 23F were determined using ELISA and opsonophagocytic activity (OPA) assay (23F) was performed, on serum samples taken immediately before and 4-6weeks after vaccination. Proportion of individuals with putative protective antibody concentration (≥1.0µg/mL) and positive antibody response (≥2-fold increase from prevaccination concentration) for both serotypes were calculated and groups were compared.
RESULTS
At baseline, 6 patients (12%) and 12 controls (24%) had protective antibody levels for both serotypes. After vaccination, antibodies increased for both serotypes in patients and controls (p<0.001), 32 patients (65%) and 35 controls (71%) reached protective level for 6B, and 32 patients (65%) and 37 controls (76%) for 23F. Compared to controls, patients had lower prevaccination geometric mean concentration (23F, p=0.01) and a numerical trend towards lower prevaccination level (6B) and postvaccination levels (both serotypes). Patients with prednisolone alone had lower prevaccination OPA (p<0.01) compared to controls. OPA increased after vaccination in both patients and controls (p<0.001), but improvement was better in controls (p=0.001). AZA, CYC or MTX, but not prednisolone alone, tended towards a lower proportion of patients reaching protective antibody levels (p=0.06), compared to controls.
CONCLUSIONS
Pneumococcal conjugate vaccine was safe and immunogenic in patients with established vasculitis. Treatment with DMARDs, mostly AZA, CYC and MTX but not systemic prednisolone may impair antibody response.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02240888. Registered 4 September, 2014.
目的
研究与健康对照相比，标准护理疗法对原发性系统性血管炎患者接种13价肺炎球菌结合疫苗（PCV13）后抗体反应和功能的影响。
方法
49例血管炎患者和49例对照者接受单剂量（0.5ml）PCV13肌肉注射。正在进行的治疗：硫唑嘌呤（AZA；n = 11）、环磷酰胺（CYC；n = 6）、甲氨蝶呤（MTX；n = 9）、利妥昔单抗（n = 3）；抗TNF（n = 2）、霉酚酸酯（n = 2）、单独使用泼尼松龙（n = 15）和未进行积极治疗（n = 2）。使用ELISA测定血清型6B和23F的特异性抗体浓度，并对疫苗接种前和接种后4 - 6周采集的血清样本进行调理吞噬活性（OPA）测定（23F）。计算两种血清型具有假定保护性抗体浓度（≥1.0μg/mL）和阳性抗体反应（比接种前浓度增加≥2倍）的个体比例，并对组间进行比较。
结果
在基线时，6例患者（12%）和12例对照者（24%）两种血清型均具有保护性抗体水平。接种疫苗后，患者和对照者两种血清型的抗体均升高（p<0.001），32例患者（65%）和35例对照者（71%）达到6B的保护性水平，32例患者（65%）和37例对照者（76%）达到23F的保护性水平。与对照者相比，患者接种前的几何平均浓度较低（23F，p = 0.01），接种前水平（6B）和接种后水平（两种血清型）有降低的数值趋势。单独使用泼尼松龙的患者接种前的OPA低于对照者（p<0.01）。患者和对照者接种疫苗后OPA均升高（p<0.001），但对照者的改善更好（p = 0.001）。与对照者相比，使用AZA、CYC或MTX（而非单独使用泼尼松龙）的患者达到保护性抗体水平的比例有降低趋势（p = 0.06）。
结论
肺炎球菌结合疫苗在已确诊的血管炎患者中是安全且具有免疫原性的。使用DMARDs（主要是AZA、CYC和MTX，但不是全身性泼尼松龙）治疗可能会损害抗体反应。
试验注册
ClinicalTrials.gov标识符：NCT02240888。于2014年9月4日注册。
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