Antibodies to Mutated Citrullinated Vimentin in Rheumatoid Arthritis: Diagnostic Value, Association with Radiological Damage and Axial Skeleton Affection

Abstract Background: Early definitive diagnosis and effective treatment are mandatory in rheumatoid arthritis (RA) as it can halt the disease progression and subsequent joints destruction. Objective: To investigate the diagnostic and prognostic value of anti-mutated citrullinated vimentin (anti-MCV) and its correlation with disease activity, peripheral and axial skeleton affection in RA patients. Patients and methods: A total of 123 patients with different rheumatic diseases were enrolled in a prospective-two year study at Ain Shams University hospital: 64 patients with RA and 59 patients with other rheumatic diseases as controls. RA patients were fulfilling the traditional and the new ACR/EULAR diagnostic criteria for RA. They have been followed up for two years. At baseline, all RA patients were subjected to: Clinical assessment of disease activity by taking full histories, general and local examination, measurement of 28 joint count of tender and swollen joints with calculation of disease activity score (DAS-28) for each patient. Complete blood count, erythrocytes sedimentation rate, C-reactive protein and rheumatoid factor titers were performed. Anti-MCV IgG immunoglobulins’ assay was performed at the study endpoint by ELISA. RA patients were then classified into; anti-MCV positive and anti-MCV negative groups for statistical comparison. Plain X-ray was performed on the peripheral joints and scored by the Simple Erosion Narrowing score (SEN-score). Magnetic Resonance Imaging (MRI) scans were carried out to 22 RA patients on cervical and lumbosacral regions. Results: Anti-MCV antibodies were found to be of high sensitivity (79.6%) and specificity (96.6%) in diagnosing RA. The area under the curve was 0.893 at 95% confidence interval (CI), confers an odds ratio of 23.5. Anti-MCV positive RA patients had significantly higher DAS-28 and SEN-scores than anti-MCV negative patients; who were found to have more benign disease with lower incidence of erosions (P , 0.05). MRI scans revealed that; 17/22 (77%) had cervical joints involvement while, 8 (36%) had lumbo-sacral joint lesions (P , 0.05), both were correlated significantly with aggressive peripheral joint disease. Conclusion: Anti-MCV antibodies are promising diagnostic and prognostic marker in RA, with high sensitivity and specificity. They may identify a subset of RA patients with aggressive early erosive disease. The axial skeleton—especially the cervical spine—could be affected in RA and this was correlated with aggressive peripheral joints’ disease. MRI scanning is a sensitive method for detecting axial skeleton involvement in RA, in attempt for better disease control and outcomes

Phytoestrogen <i>β</i>-Sitosterol Exhibits Potent In Vitro Antiviral Activity against Influenza A Viruses

Influenza is a contagious infection in humans that is caused frequently by low pathogenic seasonal influenza viruses and occasionally by pathogenic avian influenza viruses (AIV) of H5, H7, and H9 subtypes. Recently, the clinical sector in poultry and humans has been confronted with many challenges, including the limited number of antiviral drugs and the rapid evolution of drug-resistant variants. Herein, the anti-influenza activities of various plant-derived phytochemicals were investigated against highly pathogenic avian influenza A/H5N1 virus (HPAIV H5N1) and seasonal low pathogenic human influenza A/H1N1 virus (LPHIV H1N1). Out of the 22 tested phytochemicals, the steroid compounds β-sitosterol and β-sitosterol-O-glucoside have very potent activity against the predefined influenza A viruses (IAV). Both steroids could induce such activity by affecting multiple stages during IAV replication cycles, including viral adsorption and replication with a major and significant impact on the virus directly in a cell-free status “viricidal effect”. On a molecular level, several molecular docking studies suggested that β-sitosterol and β-sitosterol-O-glucoside exhibited viricidal effects through blocking active binding sites of the hemagglutinin surface protein, as well as showing inhibitory effects against replication through the binding with influenza neuraminidase activity and blocking the active sites of the M2 proton channel activity. The phytoestrogen β-sitosterol has structural similarity with the active form of the female sex hormone estradiol, and this similarity is likely one of the molecular determinants that enables the phytoestrogen β-sitosterol and its derivative to control IAV infection in vitro. This promising anti-influenza activity of β-sitosterol and its O-glycoside derivative, according to both in vitro and cheminformatics studies, recommend both phytochemicals for further studies going through preclinical and clinical phases as efficient anti-influenza drug candidates