乙型肝炎病毒在滑膜中的存在及其在类风湿关节炎中的临床意义。
Presence of hepatitis B virus in synovium and its clinical significance in rheumatoid arthritis.
机构信息
Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
出版信息
Arthritis Res Ther. 2018 Jun 19;20(1):130. doi: 10.1186/s13075-018-1623-y.
BACKGROUND
Previous studies have revealed that hepatitis B virus (HBV) infection may be related to rheumatoid arthritis (RA), but there are no studies on the presence of HBV antigens or nucleic acid in synovium from patients with RA with HBV infection. In the present study, we investigated the presence of HBV in the synovium and its clinical significance in RA.
METHODS
Fifty-seven consecutive patients with active RA (Disease Activity Score 28-joint assessment based on C-reactive protein ≥ 2.6) and available synovial tissue who had completed 1 year of follow-up were recruited from a prospective cohort. The patients were divided into chronic HBV infection (CHB, n = 11) and non-CHB groups according to baseline HBV infection status. Clinical data were collected at baseline and at 1-, 3-, 6-, and 12-month follow-up. Radiographic changes of hand/wrist at baseline and month 12 were assessed with the Sharp/van der Heijde-modified Sharp score (mTSS). HBV in synovium was determined by immunohistochemical staining for hepatitis B virus surface antigen and hepatitis B virus core antigen (HBcAg) and by nested PCR for the HBV S gene.
RESULTS
HBcAg was found in the synovium of patients with RA with CHB (7 of 11, 64%), which was confirmed by PCR for the HBV S gene. Compared with the non-CHB group, more CD68-positive macrophages, CD20-positive B cells, and CD15-positive neutrophils infiltrated the synovium in the CHB group (all p < 0.05). There were smaller improvements from baseline in most disease activity indicators mainly at month 12, and a significantly higher percentage of CHB patients experienced 1-year radiographic progression (ΔmTSS ≥ 0.5 unit/yr, 64% vs. 26%, p = 0.024). Multivariate logistic regression analysis showed that CHB status (OR 14.230, 95% CI 2.213-95.388; p = 0.006) and the density of synovial CD68-positive macrophages (OR 1.002, 95% CI 1.001-1.003; p = 0.003) were independently associated with 1-year radiographic progression.
CONCLUSIONS
The presence of HBV in RA synovium may be involved in the pathogenesis of local lesions and exacerbate disease progression in RA.
背景
先前的研究表明，乙型肝炎病毒（HBV）感染可能与类风湿关节炎（RA）有关，但目前尚无关于 HBV 抗原或核酸在 HBV 感染 RA 患者滑膜中的存在的研究。本研究旨在探讨 HBV 在 RA 滑膜中的存在及其临床意义。
方法
从前瞻性队列中招募了 57 例连续的活动性 RA 患者（基于 C 反应蛋白的 28 关节疾病活动评分≥2.6）和可获得的滑膜组织，这些患者完成了 1 年的随访。根据基线 HBV 感染状态，将患者分为慢性 HBV 感染（CHB，n=11）和非-CHB 组。在基线和 1、3、6 和 12 个月的随访时收集临床数据。使用改良 Sharp/van der Heijde Sharp 评分（mTSS）评估基线和 12 个月时的手部/腕部放射学变化。通过乙型肝炎病毒表面抗原和乙型肝炎病毒核心抗原（HBcAg）的免疫组织化学染色和乙型肝炎病毒 S 基因的巢式 PCR 来确定 HBV 在滑膜中的存在。
结果
在 CHB 组的 11 例患者中，有 7 例（64%）滑膜中存在 HBcAg，通过乙型肝炎病毒 S 基因的 PCR 得到了证实。与非-CHB 组相比，CHB 组滑膜中更多的 CD68 阳性巨噬细胞、CD20 阳性 B 细胞和 CD15 阳性中性粒细胞浸润（均 p<0.05）。在主要是 12 个月时，大多数疾病活动指标的改善幅度较小，并且 CHB 患者的放射学进展发生率显著更高（ΔmTSS≥0.5 单位/年，64%比 26%，p=0.024）。多变量逻辑回归分析表明，CHB 状态（OR 14.230，95%CI 2.213-95.388；p=0.006）和滑膜 CD68 阳性巨噬细胞密度（OR 1.002，95%CI 1.001-1.003；p=0.003）与 1 年的放射学进展独立相关。
结论
RA 滑膜中 HBV 的存在可能参与局部病变的发病机制，并加重 RA 疾病的进展。
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