Alcohol and its associated oxidative stress is one of the widespread contributors to the brain damage. Matrix metalloproteinases, which are extensively analyzed in brain pathology studies, are not sufficiently investigated in chronic alcohol consumption. This study evaluated regional brain damage caused by oxidative stress. Contribution of metalloproteinase-9 to this affection was evidenced in alcoholic subjects and correlated with ultrastructural changes. The authors found correlation between neuronal expression patterns of superoxide dismutase-1 and metalloproteinase-9 in nigral (r = 0.532, p < 0.001), striatal (r = 0.327, p < 0.001), and cortical (r = 0.306, p < 0.001) regions, and a significant decrease of nigral superoxide dismutase-1 median values accompanied by severe myelin damage.
A direct association between joint inflammation and the progression of osteoarthritis (OA) has been proposed, and synovitis is considered a powerful driver of the disease. Among infections implicated in the development of joint disease, human herpesvirus 7 (HHV-7) infection remains poorly characterized. Therefore, we assessed synovitis in OA patients; determined the occurrence and distribution of the HHV-7 antigen within the synovial membrane of OA-affected subjects; and correlated plasma levels of the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-6 (IL-6), and TNF expressed locally within lesioned synovial tissues with HHV-7 observations, suggesting differences in persistent latent and active infection. Synovial HHV-7, CD4, CD68, and TNF antigens were detected immunohistochemically. The plasma levels of TNF and IL-6 were measured by an enzyme-linked immunosorbent assay. Our findings confirm the presence of persistent HHV-7 infection in 81.5% and reactivation in 20.5% of patients. In 35.2% of patients, virus-specific DNA was extracted from synovial membrane tissue samples. We evidenced the absence of histopathologically detectable synovitis and low-grade changes in the majority of OA patients enrolled in the study, in both HHV-7 PCR+ and HHV-7 PCR‒ groups. The number of synovial CD4-positive cells in the HHV-7 polymerase chain reaction (PCR)+ group was significantly higher than that in the HHV-7 PCR‒ group. CD4- and CD68-positive cells were differently distributed in both HHV-7 PCR+ and HHV-7 PCR‒ groups, as well as in latent and active HHV-7 infection. The number of TNF+ and HHV-7+ lymphocytes, as well as HHV-7+ vascular endothelial cells, was strongly correlated. Vascular endothelial cells, especially in the case of infection reactivation, appeared vulnerable. The balance between virus latency and reactivation is a long-term relationship between the host and infectious agent, and the immune system appears to be involved in displaying overreaction when a shift in the established equilibrium develops.
The role of inflammation in the development of osteoarthritic joint degeneration is not completely understood. Recent data suggest that processes that cause and orchestrate inflamed synovial lesions may be implicated in the development of the disease. The morphological changes of the synovium in patients with osteoarthritis (OA), as well as the level of synovial inflammation cautiously graded, in association to the presence of human parvovirus B19 (B19V) infection markers, were evaluated. Qualitative and quantitative detection of B19V genomic sequence was performed in OA and rheumatoid arthritis (RA) groups. The expression of CD68, S100 (Ca2+ binding proteins soluble in 100% ammonium sulfate) and B19 VP1/VP2 capsid proteins found in the synovium were investigated by single and double immunolabeling, whereas fine features of synoviocytes — by electron microscopy. One-third of OA and RA patients demonstrated synovial expression of B19V antigen, which was confirmed in both types of synoviocytes. The overall expression of B19V in OA patients was weaker than that found in RA subjects. Positive correlation between B19V-positive vascular endothelial cells, sublining infiltrating lymphocytes, macrophages, and B19V-positive synoviocytes was established. No correlation between synovitis score indices as well as the expression of S100 and expression of B19V was found. The results suggest that the synovial membrane maintains local joint homeostasis, and that virus mediated synovitis is implicated in the development of OA.
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 DOI 10.1136/annrheumdis-2014...
Background Viral infections play a role in the pathogenesis of various forms of osteoarthritis (OA). The advanced stage of disease often manifests with severe inflammation and lesions of joint tissues related to the parvovirus B19 (B19) infection. Objectives This study aimed to demonstrate the spectra of synovial and supporting tissue damage in OA patients in association with the presence of B19 infection markers. Methods 60 OA patients and 27 age and gender matched practically healthy persons were enrolled in this study and peripheral blood (PB) samples collected. RecomLine test was used to detect of B19-specific antibodies, nPCR – to detect virus-specific sequences, proliferation test – to detect T-lymphocytes’ response to B19 antigens. From 30OA patients synovial, cartilaginous and osseous samples were obtained and conventionally processed for histopathology. B19 capsid proteins’ VP1/VP2 expression and joint tissue remodeling was assessed by immunohistochemistry, COX2 mRNA expression – by RT-PCR. Results Application of serological, molecular and immunohistochemical techniques sets up the presence of greatly varying results. No difference in the B19 specific IgG antibodies’ prevalence was found between OA patients and control group persons (83.3 and 76%, respectively), however antibodies to B19 NS1 were detected in 41.7% of OA patients vs. 3.7% of healthy persons. Anti-B19 IgM antibodies were revealed in OA patients significantly more often (30.5 vs. 8% in healthy persons). In peripheral blood/plasma DNA of 11 OA patients (18.3%) B19 genomic sequences were found. B19 sequences in PB leukocytes’ DNA were detected in OA patients only (7.7%). T-lymphocytes of OA patients responded to B19 antigens with proliferation more often and faster than control group persons confirming chronic activation of the first ones. Findings of B19 specific sequences in OA patients’ synovial tissues DNA were not unequivocal. B19 capsid protein expression was demonstrated in OA patients’ synovial, cartilaginous and osseous tissues. The red bone marrow erythroblasts, monocytes, megakaryocytes and endothelial cells showed affection evidenced by anti-B19 immunostaining. Inflammatory cells of synovial infiltrates also displayed the immunopositivity. The damage and remodeling of joint tissue was evidenced by strong immunoexpression of metalloproteinase-9 and transforming growth factor-beta found in the spongy bone, articular cartilage and synovial membrane compartments. In synovial tissues of OA patients with plasma viremia two times higher COX2 mRNA expression was shown in comparison with OA patients without viremia. Conclusions We suggest that B19 infection may contribute to the inflammatory and structural damage in the advanced stage of OA. The results proved by application of serological and molecular biological B19 infection markers should not be considered solely. These findings should be jointly implemented by immunohistochemistry data reflecting the local tissue damage and contribution of B19 to OA. Disclosure of Interest ...
BackgroundApart from systemic symptoms of viral infection parvovirus B19 (B19) could lead to acute and chronic arthropathy. It has been found in synovial tissue of rheumatoid arthritis (RA) patients, sometimes, being associated with some forms of undifferentiated arthritis. Possibly, it could promote inflammation in various forms of arthritis.ObjectivesTo determine the expression of B19 antigens in different compartments of synovial membrane; correlate these findings to the estimated synovitis score.Methods7 RA and 54 osteoarthritis (OA) patients were enrolled in this study. nPCR was used to detect the presence of B19 genomic sequence in 61 samples of synovial tissue. PCR B19 positive tissue samples were immunohistochemically treated with the anti-B19 antibodies detecting B19 capsid proteins' VP1/VP2 expression estimated thereafter semiquantitatively. The intimal and subintimal layers of synovium as well as vasculature were estimated. Synovial inflammation was evaluated using synovitis score.Results3 RA and 3 OA patients were PCR B19 tissue positive. B19 antigens' expression was observed in synovial lining, immune infiltrates and vascular endothelium. Correlation between B19 expression observed in synovial cells and inflammatory infiltrates' lymphocytes and macrophages was r=0.555 (p<0.0001) and r=0.793 (p<0.0001), respectively. Likewise, correlation between vascular endothelial B19 expression and synovial lymphocytic infiltrates was demonstrated r=0.616 (p<0.0001). Determined synovitis score varied from low up to intermediate revealing median value 2. Simultaneously, there was no correlation found between the synovitis score and B19 antigens' expression.ConclusionsB19 capsid proteins' VP1/VP2 expression is detectable in different structural constituents of synovial membrane. Under conditions studied, the tissue expression of B19 antigens does not correlate with the inflammatory indices scored.Disclosure of InterestNone declared
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