Search Results (8)

Comorbidities in tuberculosis patients are increasing annually. Autoimmune pathology may influence the diagnosis and treatment of tuberculosis (TB). However, the molecular mimicry between Mycobacterium tuberculosis (Mtb) and human autoantigens is an important provocative factor in the development of autoimmunity on one hand. Mtb has already been widely discussed as a provocateur of autoimmunity in humans. The aim of this study was to determine whether molecular mimicry exists between Mtb antigens and human autoantigens previously demonstrated as targets of autoimmunity. Materials and Methods: We analyzed the level of antibodies in 19 patients with pulmonary tuberculosis. In all cases ELISA assays was used. Also, in parallel, we identified 29 similar pentapeptides between key Mtb antigens and human autoantigens. Bioinformatic methods were used in this study. All amino acid sequences of MT antigens and human autoantigens were obtained from the UniProt database, and similar epitopes between Mtb antigens and human autoantigens were identified using the original “Alignmentaj” program. The immunoreactivity of the shared pentapeptides in Mtb antigens was evaluated with use of the IEDB database. Results: The high level of antibodies to modified citrulinated vimentin (anti-MCV) was most frequently detected (57%) in comparison with other antibodies. Elevated levels of antibodies to C3 complement fragments (47%) and rheumatoid factors (21%) in the absence of any rheumatic or autoimmune diseases are noteworthy. Several of the shared pentapeptides belong to the immunoreactive epitopes of Mtb antigens. The bioinformatic data correlated with our earlier studies of the levels of corresponding autoantibodies in the sera of TB patients. Conclusion: Our findings on cross-reactivity and sequence similarity between the Mtb proteins and human autoantigens provide support for the role of antigen mimicry in TB-related autoimmunity. Full article

With the aim of improving the uncertainties associated with the correct diagnosis of seronegative rheumatoid arthritis (RA) and identifying those at risk of developing interstitial lung disease (ILD), we have designed new peptide antigens bearing three post-translational modifications (PTMs) (citrulline, homocitrulline and acetyl-lysine) related to RA that could complement existing tests based on anti-citrullinated peptide/protein antibodies (ACPAs). Several chimeric peptides were synthesized and comparatively tested as antigens in ELISAs with two cohorts of sera: 178 RAs and 110 healthy blood donors. The results indicated that although chimeric peptides containing all three PTMs and vimentin and enolase domains do not significantly outperform existing ACPA tests in terms of sensitivity and specificity, they show potential to complement current assays, especially when detecting antibodies in some seronegative patients. Furthermore, the presence of these autoantibodies significantly identified patients with RA and ILD. We can conclude that the identification of specific autoantibody profiles using synthetic antigens containing peptide domains derived from proteins present in the human joint could help in the early detection of the risk of ILD in patients with RA and be useful for adapting follow-up strategies and guiding decisions during treatment. Full article

Elevated osteoclast (OC)-mediated bone resorption, a common pathological feature between periodontitis and rheumatoid arthritis (RA), implicates a possible mutually shared pathogenesis. The autoantibody to citrullinated vimentin (CV), a representative biomarker of RA, is reported to promote osteoclastogenesis (OC-genesis). However, its effect on OC-genesis in the context of periodontitis remains to be elucidated. In an in vitro experiment, the addition of exogenous CV upregulated the development of Tartrate-resistant acid phosphatase (TRAP)-positive multinuclear OCs from mouse bone marrow cells and increased the formation of resorption pits. However, Cl-amidine, an irreversible pan-peptidyl arginine deiminase (PAD) inhibitor, suppressed the production and secretion of CV from RANKL-stimulated OC precursors, suggesting that the citrullination of vimentin occurs in OC precursors. On the other hand, the anti-vimentin neutralizing antibody suppressed in vitro Receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced OC-genesis. The CV-induced upregulation of OC-genesis was abrogated by the Protein kinase C (PKC)-δ inhibitor Rottlerin, accompanied by the downmodulation of OC-genesis-related genes, including Osteoclast stimulatory transmembrane protein (OC-STAMP), TRAP and Matrix Metallopeptidase 9 (MMP9) as well as extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP)-kinase phosphorylation. Elevated levels of soluble CV and vimentin-bearing mononuclear cells were found in the bone resorption lesions of periodontitis induced in mice in the absence of an anti-CV antibody. Finally, local injection of anti-vimentin neutralizing antibody suppressed the periodontal bone loss induced in mice. Collectively, these results indicated that the extracellular release of CV promoted OC-genesis and bone resorption in periodontitis. Full article

Rheumatoid arthritis (RA) is a systemic chronic autoimmune inflammatory disease that is characterized by the destruction of bone and production of autoantibodies such as rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPAs). The high prevalence of this disease and the need of affordable tools for its early detection led us to prepare the first electrochemical immunoplatform for the simultaneous determination of four RA biomarkers, the autoantibodies: RF, anti-peptidyl-arginine deiminase enzyme (anti-PAD4), anti-cyclic citrullinated peptide (anti-CCP), and anti-citrullinated vimentin (anti-MCV). Functionalized magnetic beads (MBs) were used to immobilize the specific antigens, and sandwich-type immunoassays were implemented for the amperometric detection of the four autoantibodies, using the horseradish peroxidase (HRP)/H₂O₂/hydroquinone (HQ) system. The immunoplatform was applied to the determination of the biomarkers in human serum of twenty-two patients diagnosed with RA and four healthy individuals, and the results were validated against ELISA tests and the certified values. Full article

Protein citrullination and degradation by matrix metalloproteinases (MMP) plays a central role in the pathology of rheumatoid arthritis (RA). Autoantibodies are known to target citrullinated vimentin. The aim of this study was to investigate the relationship between the blood levels of MMP-degraded and citrullinated vimentin (VICM), as compared with the levels of MMP-degraded and non-citrullinated vimentin (VIM), and the standard anti-CCP biomarker in RA patients undergoing treatment. Thus, VIM, VICM and anti-CCP were quantified by ELISA in serum samples from baseline and week 8 of patients (n = 257) with RA, treated with either tocilizumab (8 mg/kg), methotrexate (7.5–15 mg/kg) or a placebo and compared with a reference cohort (n = 64). The three biomarkers were elevated in RA serum compared with the reference cohort: medians were 1.7 vs. 0.8 ng/mL (p < 0.05) for VIM; 7.5 vs. 0.7 ng/mL (p < 0.0001) for VICM; 57 vs. 4 RU/mL (p < 0.001) for anti-CCP. VICM was decreased in response to tocilizumab (2.9-fold, p < 0.0001) and to methotrexate (1.5-fold, p < 0.05) compared with the placebo, while anti-CCP was not. Serum VIM was also modulated by both drugs, although to a lesser degree. A high baseline level of VICM was predictive of a low disease activity response at week 8. In conclusion, VICM can differentiate between RA and healthy donors in a similar manner to anti-CCP; furthermore, VICM is also a pharmacodynamic marker. Full article

There is a need to further characterize the antibody response to vimentin in relation to its possible involvement in pathogenicity of sarcoidosis and other lung disorders. Objectives: We investigated serum samples from patients with sarcoidosis, healthy controls and controls with other non-infectious lung diseases., to evaluate levels and frequency of these antibodies. Materials and methods: A retrospective-prospective comparative study was performed in the years 2015–2019. Sera from 93 patients with sarcoidosis, 55 patients with non-infectious lung diseases and 40 healthy subjects was examined for presence of autoantibodies to mutated citrullinated vimentin (anti-MCV). Patients with elevated anti-MCV levels were tested for antibodies to a cyclic citrullinated peptide (anti-CCP) and citrullinated vimentin (anti-Sa). In all cases ELISA assays was used. The results were considered statistically significant at p-value less than 0.05. Results of the study: The high concentrations of anti-MCV antibodies were more frequent in patients with sarcoidosis (40.9% of the cases, 38/93), compared to the control groups (23.6% and 25.0% of cases, respectively). In sarcoidosis, clinical symptoms similar to the autoimmune pathology were described. A moderate positive correlation between the anti-MCV and anti-Sa antibodies (r = 0.66) was found in 13 patients with sarcoidosis. There was no significant difference between the levels of the anti-MCV and the anti-CCP in patients with non-infectious lung diseases and the healthy control group. Conclusion: Antibodies to citrullinated cyclic peptides are not significant in the pathogenesis of sarcoidosis and other investigated pulmonary diseases (COPD, granulomatosis with polyangiitis, alveolitis) and based on their low concentration, it can be assumed that citrullination and modification of vimentin is not a key factor in the development of an autoimmune response in patients with sarcoidosis. Full article

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed. Full article

A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM. Full article