Primary Sjögren's syndrome (pSS) is characterized by B cell hyperactivation, production of autoantibodies and increased risk of B cell lymphomas. Serological profile of Epstein-Barr virus (EBV) reactivation and increase EBV DNA levels in exocrine glands are observed in pSS, but whether these abnormalities are accompanied with disturbed systemic EBV control or have any association with pSS activity remains to be investigated. In this observational study, we initially explored anti-EBV antibodies and cell-free DNA in 395 samples from a cross-sectional plasma collection of pSS patients included in ASSESS French national cohort. Results were assessed in relation with disease activity. Further, to assess cell-associated EBV DNA we organized a case-control study including 20 blood samples from pSS patients followed in University Hospital Center of Montpellier. Results were compared with matched controls. Robust response against EBV early antigen (EA) was observed in pSS patients with anti-SSA/B (Sjögren's syndrome A and B) and anti-SSA autoantibodies compared to anti-SSA/B negatives ( P < 0.01 and P = 0.01, respectively). Increased beta-2 microglobulin, kappa and lambda light chains, and immunoglobulin G levels were more frequently observed in anti-EA seropositive pSS subjects compared to anti-EA negative subjects ( P < 0.001; P = 0.001; P = 0.003, respectively). Beta-2 microglobulin was independently associated with anti-EA positivity in multivariate analysis ( P < 0.001). Plasma cell-free EBV DNA and EBV cellular reservoir was not different between pSS patients and controls. We conclude that serological evidence of EBV reactivation was more frequently observed and more strongly associated with anti-SSA/B status and B cell activation markers in pSS. However, serological profile of EBV reactivation was not accompanied by molecular evidence of systemic EBV reactivation. Our data indicated that EBV infection remains efficiently controlled in the blood of pSS patients.
BackgroundCompared with the general population, patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease or events (CE): stroke, Myocardial Infarction (MI), Congestive Heart Failure (CHF) and Cardiovascular Mortality (CVM). Systemic inflammation is the cornerstone of both RA and atherosclerosis. Over the past fifteen years, new treatment strategies such as tight control, treat to target, methotrexate optimization, biologic DMARDs use has allowed a better control of this inflammation.ObjectivesThe aim of this systematic review was to assess the excess risk of presenting a CE in RA patients as compared to general population, before and after the 2000s.MethodsWe systematically searched literature (via Pubmed, Cochrane and abstracts from recent ACR and EULAR congresses) up to March 2016 for observational studies providing data about the occurrence of a CE (among stroke, MI, CHF, CVM) in patients with RA and in a control group. A meta-analysis of the relative risk (RR) concerning patients with RA in relation to the control group was performed for each cardiovascular event and for each period (before and after the 2000s).ResultsOut of 5714 screened references, 28 studies were included. For studies published before 2000, an increased risk of CEs was observed in RA patients:– RR=1.12 [95% CI 1.04; 1.21], p=0.002 for stroke– RR=1.25 [1.14; 1.37], p<0.00001 for CHF– RR=1.21 [1.15; 1.26], p<0.00001 for CVM– RR=1.32 [1.24; 1.41], p<0.00001) for MI.For all studies published after the year 2000, the increased risk was not retrieved for CHF (RR=0.58 [0.11; 3.55], p=0.52) and CVM (RR=1.07 [0.74; 1.56], p=0.71). The excess risk of MI was reduced in comparison with the period before 2000: RR=1.18 [1.14; 1.23], p<0.00001.The excess risk of stroke was stable: RR=1.23 [1.06; 1.43], p=0.006.Discussion: This meta-analysis confirms an increased risk of CEs among people with RA relative to the general population. It also appears that this excess risk is less prevalent than prior to 2000s. This might have two explanations: a better management of the cardiovascular risk in patients with RA and a better control of chronic systemic inflammation thanks to new therapeutic strategies.ConclusionsThe cardiovascular excess risk of RA patients relative to the general population has decreased since 2000s. This suggests that the recent improvements in RA management may have a positive impact on cardiovascular comorbidities.Disclosure of InterestNone declared
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