Effect of Human Herpesviruses 6 and 7 Infection on the Clinical Course of Rheumatoid Arthritis / Cilvēka Herpesvīrusa 6 Un 7 Infekcijas Ietekme Uz Reimatoīdā Artrīta Klīnisko Gaitu

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease affecting joints and causing symmetrical chronic progressive aseptic synovitis and erosive-destructive changes. Viruses and viral infections are considered to be the main risk factors for autoimmune disease development (especially for individuals with genetic predisposition). The goal of this study was to evaluate the frequency of HHV-6 and HHV-7 persistent infection and its activity phase in RA and osteoarthritis (OA) patients, and healthy persons. We examined also the influence of HHV-6 and -7 infections on RA activity, aggressiveness, radiographical stage, and frequency of complications as well as the presence of HHV-6 infection markers in synovial fluid and synovial tissues of RA joints of affected patients. Despite the lack of significant correlation between frequency of persistent single HHV-6, single HHV-7, and concurrent HHV-6 and HHV-7 infection and RA clinical course, we found that both active and latent HHV-6 and/or HHV-7 infection increased RA activity and progression in several clinical and laboratory parameters. Regarding the severity of the course of RA, we observed also a high prevalence of RA complications in the patient group with active single HHV-6 infection and also a more severe radiographical stage in RA patients with active concurrent HHV-6 and HHV-7 infection. Moreover, viral infection markers were found in synovial fluid and synovial tissues of affected joints of RA patients. This suggests that HHV-6 and/or HHV-7 infection has effect on the disease clinical course, but virus reactivation may be a consequence of immunosuppressive treatment.

From Viral Infection to Autoimmune Reaction: Exploring the Link between Human Herpesvirus 6 and Autoimmune Diseases

“…Another study demonstrated that HHV-6 DNA could be detected in synovial tissues and fluid, and antigens could be visualized in synovial tissues of RA patients by immunohistochemistry, albeit the tissues analyzed were from a small number of RA patients. The same study demonstrated some connection between HHV-6 infection and RA disease activity [ 98 ]. Conversely, another study analyzing RA patients’ synovial fluid could not detect HHV-6 DNA [ 99 ].…”

Inflammatory Cytokine-Producing Cells and Inflammation Markers in the Synovium of Osteoarthritis Patients Evidenced in Human Herpesvirus 7 Infection

“…The results of several studies have confirmed the presence of human herpesvirus 6 (HHV-6) and 7 (HHV-7) DNA and viral antigens by polymerase chain reaction (PCR) techniques, in situ hybridization, immunohistochemistry, and electron microscopy in blood plasma, peripheral blood mononuclear cells, the brain, and skin [ 25 , 26 , 27 , 28 , 29 , 30 ]. Furthermore, our earlier study reported on the presence of human HHV-6 and HHV-7 infection markers in synovial fluid and synovial tissues of rheumatoid arthritis (RA)-affected patients [ 31 ]. HHV-6A, HHV-6B, and HHV-7 are genetically related to human cytomegalovirus (HCMV) constituting the β-herpesvirus subfamily [ 22 , 32 ].…”