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Abstract：
The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren\'s syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3-4/Day5-6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14-28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.
摘要：
本研究旨在调查羟氯喹（HCQ）处理是否会影响中和抗体的产生，原发性干燥综合征（pSS）计划的17DD-黄热病（YF）初免疫苗（Bio-Manguinhos-FIOCRUZ）时的病毒血症水平和血清可溶性介质动力学。共纳入34名pSS患者和23名健康对照(HC)。pSS组根据HCQ(HCQ和非HCQ)的使用进一步分类。YF-斑块减少中和试验(PRNT≥1:50),在基线和随后的时间点(Day0/Day3-4/Day5-6/Day7/Day14-D28)进行YF病毒血症(RNA贫血)和血清生物标志物分析。pSS组的PRNT滴度和血清阳性率与HC相似（GeoMean=238vs440，p=.11；82％vs96％，p=.13）。然而,与HC相比，HCQ亚组的血清转化率较低（地质平均值=161vs440，p=.04；69%vs96%，p=.02）和非HQC（地质平均值=161vs337，p=.582；69%vs94%，p=.049）。亚组之间未观察到YF病毒血症的差异。血清生物标志物分析表明，HCQ亚组表现出CCL2，CXL10，IL-6，IFN-γ，IL1-Ra,IL-9、IL-10和IL-2在基线处,并且沿着动力学时间线显示出几种生物标志物的一致增加,直到D14-28。这些结果表明,与非HCQ亚组相比,HCQ亚组在由17DD-YF原基接种引发的组装YF特异性免疫应答中表现出缺陷。我们的发现表明，羟氯喹与17DD-YF原始疫苗接种后体液免疫反应的降低有关。
