Abstract

Chronic inflammatory rheumatic diseases (CIRDs) are immune-mediated pathologies involving joints. To date, TNFα-blocking agents administration is the most promising therapy, although these treatments are associated with an increased Polyomavirus JC (JCPyV) reactivation, the etiological agent of the Progressive Multifocal Leukoencephalopathy (PML). The aim of this study was the recruitment and the analysis of a CIRDs cohort in order to investigate a possible correlation between JCPyV presence and the influence of anti-TNF-α agents on viral loads. Blood and urine samples were collected from 34 CIRDs subjects prior the first anti-TNF-α infusion (T0) and after 3 (T3), 6 (T6), 12 (T12), and 18 (T18) months. Results showed persistent JC viruria significantly higher than JC viremia throughout the 18 month follow-up study (p = 0.002). In JCPyV positive samples, the non-coding control region (NCCR) was analyzed. Results evidenced archetypal structures (type II-S) in all isolates with the exception of a sequence isolated from a plasma sample, that corresponds to the type II-R found in PML subjects. Finally, the viral protein 1 (VP1) genotyping was performed and results showed the prevalence of the European genotypes 1A, 1B, and 4. Since only few studies have been carried out to understand whether there is a PML risk in CIRDs population infected by JCPyV, this study contributes to enrich literature insight on JCPyV biology in this cluster. Further investigations are necessary in order to recognize the real impact of biologics on JCPyV life cycle and to identify possible and specific viral variants related to increased virulence in CIRDs patients.

Highlights

  • Chronic Inflammatory Rheumatic Diseases (CIRDs) are severe and chronic pathologies that cause deterioration of the quality of life and place a major burden on health care systems worldwide (Mócsai et al, 2014).Rheumatic Arthritis (RA) is a multiple joints inflammatory disease associated with an increased mortality when autoantibodies can be detected in the serum (Gerlag et al, 2015; Lahiri and Dixon, 2015)

  • 34 subjects affected by Chronic inflammatory rheumatic diseases (CIRDs) (12 males, 22 females) were dynamically enrolled

  • Q-PCR revealed that 16/34 (47.1%) urine were JCPyV-positive with a median value of 6.73 log10/ml (Tables 3, 4)

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Summary

Introduction

Chronic Inflammatory Rheumatic Diseases (CIRDs) are severe and chronic pathologies that cause deterioration of the quality of life and place a major burden on health care systems worldwide (Mócsai et al, 2014).Rheumatic Arthritis (RA) is a multiple joints inflammatory disease associated with an increased mortality when autoantibodies can be detected in the serum (Gerlag et al, 2015; Lahiri and Dixon, 2015). Chronic Inflammatory Rheumatic Diseases (CIRDs) are severe and chronic pathologies that cause deterioration of the quality of life and place a major burden on health care systems worldwide (Mócsai et al, 2014). Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects 1% of the general population. Psoriatic arthritis (PsA) is a systemic inflammatory arthritis characterized by chronic and progressive disease leading to lost productivity and reduced quality of life. PsA is a distinct disease respect to RA and AS, disease-modifying anti-rheumatic drugs (DMARDs) were introduced into the therapy of all these inflammatory rheumatic diseases to provide symptomatic improvement and to progress or maintain quality of life (Moll and Wright, 1973; Bijlsma, 2012). Methotrexate (MTX) is the DMARD most widely used and it remains the first line therapy its cytotoxic nature and/or partial efficacy limit its use (Mócsai et al, 2014)

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