Background Erosions of articular cartilage and the associated release of mucopolysacharides have important role of the joint destruction in rheumatoid arthritis (RA) and osteoarthritis (OA). Pathophysiology of these diseases is associated with the accumulation of inflammatory mediators in the joint space. There are many initiating factors including viral infections what can trigger development of arthritis.
Objectives Our work aims to analyze the presence of MMP-9 and its regulation by local tissue mediators at the synovia, articular cartilage, and bone of RA and OA patients with various B19 and beta-herpesviruses antigen expression.
Methods 51 RA and 56 OA patients and 19 healthy control group individuals were enrolled in this study and peripheral blood samples collected. RecomLine B19 IgG and IgM tests were used to detect IgG and IgM class antibodies, nPCR – to detect B19, HHV-6 and HHV-7 genomic sequences, quantitative ELISA - to detect MMP-9 level in peripheral blood. Tissues were formalin fixed and paraffin-embedded. MMP-9 and transforming growth factor beta (TGF-beta) immunolabeling was used for estimation of events within affected joints. B19 capsid proteins' VP1/VP2 and HHV-6 expression were assessed by immunohistochemistry, presence of viral DNA - by nPCR.
Results The markers of B19 infection were more frequently detected in RA patients in comparison to OA patients and healthy individuals (p=0.0018). Active B19 infection was observed in 51% of RA patients versus 14.3% in OA patients (p=0.0001) and 8.3% in control group (p=0.0003). Anti-B19 IgG class antibodies were found in all RA patients with active infection. The viremia in most cases was without virus specific IgM, but with the presence of anti-B19 IgG class antibodies. HHV-6 viral genomic sequence was significantly more often detected in RA patients synovial tissues 50% versus OA patients synovial tissues 9.4% (p=0.0387). No significant differences between the groups were found in prevalence of HHV-7 genomic sequence. The mean level of MMP-9 was higher in RA patients in comparison with control group (p=0.03). Moderate to strong MMP-9 expression was demonstrated in the synovial membrane, vasculature, cartilage and inflammatory infiltrates reflecting ongoing remodeling process. The above mentioned locations were overlapped by TGF-beta expression indicative of its role in the changes taking place in the affected joints. HHV-6 antigen expressed as cytoplasmic staining was detected within cells constituting synovial membrane, cartilage, bone, blood vessel wall, inflammatory infiltrates, whereas, B19 capsid proteins' VP1/VP2 – as nuclear staining in the synovial cells, endotheliocytes, vascular myocytes, and the red bone marrow cells.
Conclusions B19 and HHV-6 antigen expression suggests that these viral agents are involved in the perpetuation of synovitis, leading to joint lesions. The detected expression of MMP-9 and TGF-beta reflects joint changes in patients with RA and OA.
Disclosure of Interest None declared