Abstract
The present study aims to clarify the possible involvement of parvovirus B19 (B19V) infection in rheumatoid arthritis (RA) pathogenesis by investigating the presence of B19V infection markers (genomic sequences and virus-specific antibodies) in association with the level of cytokines and RA clinical activity and aggressiveness. A total of 118 RA patients and 49 age- and sex-matched healthy volunteers were enrolled in the study. Nested PCR was used to detect B19V sequences in whole blood and cell-free plasma DNA, ELISA to detect virus-specific antibodies and cytokine levels in plasma and recomLine dot blot assay for antibodies to separate B19V antigens. The detection frequency of B19V DNA was higher in patients with RA (25.4 %) in comparison with healthy persons (18.4 %). B19V DNA in cell-free plasma (B19+p) was detected significantly often in RA patients in comparison with healthy controls (13.6 vs 2 %; P=0.0002). RA B19+p patients had higher disease activity and aggressiveness, decreased haemoglobin and increased erythrocyte sedimentation rates. IL-6 plasma levels were significantly higher in RA patients than in controls. Within the RA patients’ group the IL-6 level was significantly increased in B19+p patients with disease activity scores of DAS28>5.2, high C-reactive protein and low haemoglobin. Contrary to the healthy controls, the majority of RA B19+p patients did not have antibodies to VP-1S (VP1u) and VP-N (N-terminal half of structural proteins VP1 and VP2), which correspond to the epitopes of neutralizing antibodies. These results indicate that B19V infection at least in some patients is involved in RA pathogenesis.
Highlights
Human parvovirus B19 (B19V) is a small DNA virus with a worldwide distribution
In this study we investigated the frequency of B19V infection markers in the blood of rheumatoid arthritis (RA) patients
Our results showed that the frequency of B19V latent/persistent (B19V sequences presented only in DNA extracted from the whole blood) and active (B19V sequences presented in DNA extracted from the cell-free blood plasma) infection markers is different in RA patients and healthy people (Table S1, available in the online Supplementary Material)
Summary
Human parvovirus B19 (B19V) is a small DNA virus with a worldwide distribution. The genome of B19V consists of single-stranded 5.6 kb DNA that encodes three large proteins. B19V is normally transmitted through the respiratory route, but can be transmitted from the mother to the foetus (Berry et al, 1992; Brown et al, 1984; Clewley et al, 1987; Kinney et al, 1988; Musiani et al, 1999), through bone marrow (Cohen et al, 1997; Heegaard & Laub Petersen, 2000; Ozawa & Young, 1987) and organ transplantations (Bertoni et al, 1997; Lui et al, 2001), and via transfused blood products (Juhl et al, 2014). B19V DNA was found in peripheral blood and synovial fluid cells (Kozireva et al, 2008), and VP1 protein was detected in synovial cells ã 2016 The Authors Printed in Great Britain
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