Anti-vimentin antibodies in transplant and disease

Divanyan, Tigran; Acosta, Ernesto; Patel, Dhruv; Constantino, Don; Lopez‐Soler, Reynold I.

doi:10.1016/j.humimm.2019.03.017

Cited by 23 publications

(15 citation statements)

References 53 publications

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“…Vimentin is an intermediate filament protein that, when polymerized, forms the basis of the fibroblast, smooth muscle cell, and endothelial cell cytoskeletons. It participates in signal transduction, maintenance of cell structure, cell motility, and cell proliferation [14]. There is evidence showing that anti-vimentin antibodies are associated with interstitial fibrosis/tubular atrophy and transplant glomerulopathy after kidney transplantation [10-12].…”

Section: Discussionmentioning

confidence: 99%

Chronic Active Antibody-Mediated Rejection with Linear IgG Deposition on Glomerular Capillaries in a Kidney Transplant Recipient

Miura

Shirai

Kaneko

et al. 2020

Nephron

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Glomerular IgG deposition is rarely observed in antibody-mediated rejection. Here, we report chronic active antibody-mediated rejection with linear IgG deposition on glomerular capillary walls in a pediatric kidney transplant recipient. A 6-year-old boy with bilateral renal hypoplasia underwent preemptive deceased-donor kidney transplantation. Five years after the transplantation, an allograft biopsy revealed chronic active antibody-mediated rejection with diffuse linear IgG deposition on glomerular capillaries. Anti-glomerular basement membrane antibody, donor-specific anti-human leukocyte antigen (HLA) antibodies, and anti-angiotensin II type 1 receptor antibody were negative. A multiplex antibody assay identified anti-major histocompatibility complex class I chain-related molecule A antibody. Additionally, a single-antigen bead assay identified autoantibodies to 12 non-HLA antigens, including vimentin and glutathione S-transferase theta-1. To investigate whether IgG autoantibodies in the patient’s serum bind to antigens on glomerular capillaries, we incubated the patient’s serum with 0-h biopsy specimens of tissue donated to the patient and a control subject, both obtained immediately after nephrectomy from respective donors. IgG signals were observed in neither patient nor control samples. Nevertheless, linear IgG deposition may be explained by the binding of autoantibodies to non-HLA antigens that are usually hidden and only exposed via severe endothelial cell injury. Further studies are needed to confirm the significance of non-HLA antibodies in glomerular IgG deposition.

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Section: Discussionmentioning

confidence: 99%

Chronic Active Antibody-Mediated Rejection with Linear IgG Deposition on Glomerular Capillaries in a Kidney Transplant Recipient

Miura

Shirai

Kaneko

et al. 2020

Nephron

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“…Indeed, these modifications could lead to the exposure of epitopes not usually accessible to the immune system and trigger an immune reaction. Anti-vimentin autoantibodies (AVA) have been detected in situations associated with tissue damage, such as chronic hemodialysis, and in transplant rejection [97] (for a recent review, see [98]). Moreover, they have a prognostic character in several pathological conditions.…”

Section: Vimentin In Immune Responsesmentioning

confidence: 99%

Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections

Ramos

Stamatakis

Oeste

et al. 2020

IJMS

133

121

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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.

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“…Anti-vimentin antibodies detected before KTx, probably reflecting previous endothelial damage occurred during hemodialysis, have also been associated with graft dysfunction [ 126 ].…”

Section: Armentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

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New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.

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Anti-vimentin antibodies in transplant and disease

Cited by 23 publications

References 53 publications

Chronic Active Antibody-Mediated Rejection with Linear IgG Deposition on Glomerular Capillaries in a Kidney Transplant Recipient

Chronic Active Antibody-Mediated Rejection with Linear IgG Deposition on Glomerular Capillaries in a Kidney Transplant Recipient

Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

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