Antibodies to vimentin intermediate filaments in sera from patients with systemic lupus erythematosus

Alcover, Andrés; Molano, Jesús; Renart, Jaime; Gil‐Aguado, Antonio; Nieto, Antonio; Ávila, Jesús

doi:10.1002/art.1780270812

Cited by 50 publications

(25 citation statements)

References 25 publications

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“…Four of the six identified proteins, vimentin, hsp 60, ␣-enolase, and nucleophosmin, were previously shown to be the targets of autoantibodies produced in human or mouse nonorgan-specific autoimmune diseases. For example, anti-vimentin Abs have already been described in SLE patients (20,21) and their presence was positively correlated with that of anti-CL Abs (22), an observation similar to that made in this study for male WB mice. Similarly, antinucleophosmin autoantibodies were previously detected in SLE patients, and were shown to be constantly associated with the presence of anti-CL Abs (23).…”

Section: Discussionsupporting

confidence: 90%

Orderly Pattern of Development of the Autoantibody Response in (New Zealand White × BXSB)F1 Lupus Mice: Characterization of Target Antigens and Antigen Spreading by Two-Dimensional Gel Electrophoresis and Mass Spectrometry

Thebault

Gilbert

Hubert

et al. 2002

The Journal of Immunology

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Immunoblots of a two-dimensional PAGE-separated HL-60 cell proteomic map and mass spectrometry were combined to characterize proteins targeted by autoantibodies produced by male (New Zealand White × BXSB)F1 (WB) mice that develop lupus and anti-phospholipid syndrome. Analysis of sera sequentially obtained from seven individual mice at different ages showed that six proteins, vimentin, heat shock protein 60, UV excision-repair protein RAD23, α-enolase, heterogeneous nuclear ribonucleoprotein L, and nucleophosmin, were the targets of the B cell autoimmune response, and that autoantibodies to them were synthesized sequentially in an orderly pattern that recurred in all the male WB mice analyzed: anti-vimentin first and anti-nucleophosmin last, with anti-RAD23 and anti-heat shock protein 60, then anti-α-enolase and anti-heterogeneous nuclear ribonucleoprotein L Abs occuring concomitantly. Anti-vimentin reactivity always appeared before anti-cardiolipin and anti-DNA Abs, suggesting that vimentin is the immunogen initiating the autoimmune process. The pattern of HL-60 proteins recognized by female WB sera differed from that of male sera, indicating that the Y chromosome-linked autoimmune acceleration gene is not an accelerator but a strong modifier of the autoimmune response. Thus, 1) combining two-dimensional PAGE and mass spectrometry constitutes a powerful tool to identify the set of Ags bound by autoantibodies present in a single serum and the whole autoantibody pattern of an autoimmune disease; 2) the diversification of the autoimmune response in male WB mice occurs in a predetermined pattern consistent with Ag spreading, and thus provides a useful model to further our understanding of the development of the autoantibody response in lupus.

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Section: Discussionsupporting

confidence: 90%

Orderly Pattern of Development of the Autoantibody Response in (New Zealand White × BXSB)F1 Lupus Mice: Characterization of Target Antigens and Antigen Spreading by Two-Dimensional Gel Electrophoresis and Mass Spectrometry

Thebault

Gilbert

Hubert

et al. 2002

The Journal of Immunology

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“…Anticytoskeletal antibodies (ACY) have been reported to occur in various human sera (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). These reports did not establish a significant functional or diagnostic relationship between the presence of particular antibodies and the occurrence of a particular disease.…”

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confidence: 99%

Anticytoskeletal autoantibodies in the connective tissue diseases

Senécal

Oliver

Rothfield

1985

Arthritis & Rheumatism

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The sera of 103 patients with connective tissue diseases were studied for the presence of anticytoskeletal antibodies by using an indirect immunofluorescence method. PTK2 cells fixed with paraformaldehyde and digitonin were used as substrate. Antibodies to intermediate filaments were detected in sera of 85.7% of polymyositis/dermatomyositis (PMIDM), 62.8% of systemic sclerosis, 54.5% of rheumatoid arthritis, and 37.5% of systemic lupus erythematosus patients, and in 42.5% of normal sera. High titers of these antibodies, which were IgM, were present in 30% of patients' and 5% of normal sera. Antibodies to microfilaments were present in 11.6% of patients' sera and absent in all control sera. These antibodies were IgM or IgG. The switch from an IgM to an IgG antibody was observed in 1 patient. An IgG antibody to the spindle poles and midbody of mitotic cells was present in the serum of 1

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“…Under these conditions, ubiquitous structural proteins can become the target of a secondary immune response, as exemplified by cytotoxic T lymphocyte (CTL) priming against vinculin from apoptotic cells [33]. Another example is the detection of autoantibodies against vimentin in lupus patients or CD8 T cell reactivity against that protein in cardiac transplant patients [34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Incidental CD8 T cell reactivity against caspase-cleaved apoptotic self-antigens from ubiquitously expressed proteins in islets from prediabetic human leucocyte antigen-A2 transgenic non-obese diabetic mice

Coppieters

Amirian

Herrath

2011

Clinical and Experimental Immunology

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SummaryApoptosis is known as a major mechanism which contributes to beta cell decay in type 1 diabetes. Commitment to this pathway generally involves caspase-mediated protein cleavage and was found to induce crosspresentation of a specific antigen repertoire under certain inflammatory conditions. We aimed to assess the significance of the CD8 T cell population reactive against such caspase-cleaved apoptotic self-antigens in pancreatic islets of prediabetic human leucocyte antigen (HLA)-A2 transgenic non-obese diabetic chimeric monochain transgene construct (NOD.HHD) mice. We have reproduced a unique peptide library consisting of human CD8 T cellderived apoptosis-specific antigens, all of which belong to structural proteins expressed ubiquitously in human islets. Pancreatic islets from prediabetic NOD.HHD mice, harbouring humanized major histocompatibilty complex (MHC) class I, were isolated and handpicked at various ages, and isletinfiltrating CD8 T cells were expanded in vitro and used as responders in an interferon (IFN)-g enzyme-linked immunospot (ELISPOT) assay. Human T2 cells were used as antigen-presenting cells (APC) to avoid endogenous antigen presentation. Analogous to the interindividual variability found with peptides from known islet autoantigens such as islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) and insulin, some mice showed variable, low-degree CD8 T cell reactivity against caspase-cleaved self-antigens. Because reactivity was predominantly minor and often undetectable, we conclude that beta cell apoptosis does not routinely provoke the development of dominant cytotoxic T lymphocyte (CTL) reactive against caspase-cleaved selfantigens in the NOD.HHD model.

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Antibodies to vimentin intermediate filaments in sera from patients with systemic lupus erythematosus

Cited by 50 publications

References 25 publications

Orderly Pattern of Development of the Autoantibody Response in (New Zealand White × BXSB)F1 Lupus Mice: Characterization of Target Antigens and Antigen Spreading by Two-Dimensional Gel Electrophoresis and Mass Spectrometry

Orderly Pattern of Development of the Autoantibody Response in (New Zealand White × BXSB)F1 Lupus Mice: Characterization of Target Antigens and Antigen Spreading by Two-Dimensional Gel Electrophoresis and Mass Spectrometry

Anticytoskeletal autoantibodies in the connective tissue diseases

Incidental CD8 T cell reactivity against caspase-cleaved apoptotic self-antigens from ubiquitously expressed proteins in islets from prediabetic human leucocyte antigen-A2 transgenic non-obese diabetic mice

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