Presence of hepatitis B virus in synovium and its clinical significance in rheumatoid arthritis

Abstract

BackgroundPrevious 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.MethodsFifty-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.ResultsHBcAg 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.ConclusionsThe presence of HBV in RA synovium may be involved in the pathogenesis of local lesions and exacerbate disease progression in RA.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1623-y) contains supplementary material, which is available to authorized users.

Methotrexate an Old Drug with New Tricks

“…Arthritis occurs during both the acute and chronic HBV infection [5]. HBcAg was found in the synovium of patients with RA with chronic HBV infection [227]. The presence of HBV in RA synovium was suggested to be involved in the pathogenesis of RA [227].…”

“…HBcAg was found in the synovium of patients with RA with chronic HBV infection [227]. The presence of HBV in RA synovium was suggested to be involved in the pathogenesis of RA [227]. Some cases of HBV reactivation after MTX therapy in HBsAg-positive patients have been reported in the rheumatology literature mainly in the form of case reports [228,229].…”

Addition of Fibroblast-Stromal Cell Markers to Immune Synovium Pathotypes Better Predicts Radiographic Progression at 1 Year in Active Rheumatoid Arthritis

“…Patients with RA according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria ( 26 ) were recruited between May 2010 and August 2020 from a real-world prospective cohort carried in the Department of Rheumatology, Sun Yat-Sen Memorial Hospital as we previously reported ( 7 , 27 , 28 ). Inclusion criteria included RA patients who had a synovial biopsy at baseline and had finished regular visits at 1 year.…”

“…Inclusion criteria included RA patients who had a synovial biopsy at baseline and had finished regular visits at 1 year. RA patients overlapping other autoimmune diseases were excluded ( 7 , 27 ). All patients were treated according to the EULAR recommendations of the “treat-to-target” strategy.…”

“…Available demographic and clinical data were collected at baseline and at 1-, 3-, 6-, and 12-month visits, as previously described ( 7 , 27 , 28 ). Disease activity was categorized into four states according to the Clinical Disease Activity Index (CDAI): high (>22), moderate (10~22), low (2.8~10), and remission (≤2.8).…”