Antibodies in scleroderma: Direct pathogenicity and phenotypic associations

Chung, Lorinda; Utz, Paul J.

doi:10.1007/s11926-004-0061-9

Cited by 58 publications

(52 citation statements)

References 45 publications

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“…The present study substantiates and extends several other reports that collectively show that IPF is often complicated by the presence of autoreactive T cells, as well as diverse autoantibodies that have various associations with clinical manifestations (2-10, 13, 16). These particular characteristics also typify conventional autoimmune syndromes (43)(44)(45). As examples, dozens of autoantibodies Those who had greater than average levels of both autoantibodies (Both High, n = 10) had lesser FVC percentage predicted than did the other patients (Other) who had only a single or no increased autoantibody concentration.…”

Section: Discussionmentioning

confidence: 99%

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis

Surolia

et al. 2017

The Journal of Immunology

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Autoimmunity has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, the repertoire of autoantigens involved in this disease and the clinical relevance of these autoimmune responses are still being explored. Our initial discovery assays demonstrated that circulating and intrapulmonary vimentin levels are increased in IPF patients. Subsequent studies showed native vimentin induced HLA-DR–dependent in vitro proliferation of CD4 T cells from IPF patients and enhanced the production of IL-4, IL-17, and TGF-β1 by these lymphocytes in contrast to normal control specimens. Vimentin supplementation of IPF PBMC cultures also resulted in HLA-DR–dependent production of IgG with anti-vimentin specificities. Circulating anti-vimentin IgG autoantibody levels were much greater in IPF subjects from the University of Alabama at Birmingham (n = 102) and the University of Pittsburgh (U. Pitt., n = 70) than in normal controls. Anti-vimentin autoantibody levels in IPF patients were HLA biased and inversely correlated with physiological measurements of lung function (i.e., forced expiratory volumes and diffusing capacities). Despite considerable intergroup differences in transplant-free survival between these two independent IPF cohorts, serious adverse outcomes were most frequent among the patients within each population that had the highest anti-vimentin autoantibody levels (University of Alabama at Birmingham: hazard ratio 2.5, 95% confidence interval 1.2–5.3, p = 0.012; University of Pittsburgh: hazard ratio 2.7, 95% confidence interval 1.3–5.5, p = 0.006). These data show that anti-vimentin autoreactivity is prevalent in IPF patients and is strongly associated with disease manifestations. These findings have implications with regard to the pathogenesis of this enigmatic disease and raise the possibility that therapies specifically directed at these autoimmune processes could have therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis

Surolia

et al. 2017

The Journal of Immunology

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“…The four plasma samples which showed a centromere pattern by ANA IIF were positive for anti-CENP-B as would be expected but were also positive for anti-Scl70 and anti-dsDNA. Such findings would be rare in a population of humans with SSc, in which the majority of patients would have developed autoantibodies only to Scl70 or CENP-B and not to multiple autoantigens (1,3,4). Although the finding that almost all of the Tsk2/ϩ mice develop autoantibodies to anti-Scl70 or anti-CENP-B is certainly similar to what has been reported for SSc, the fact that the mouse develops multiple autoantibodies to both of these Ags in 52 of the 60 Tsk2/ϩ plasma samples is a remarkable difference from what happens in humans (1,3,7,22).…”

Section: Discussionmentioning

confidence: 99%

“…Such findings would be rare in a population of humans with SSc, in which the majority of patients would have developed autoantibodies only to Scl70 or CENP-B and not to multiple autoantigens (1,3,4). Although the finding that almost all of the Tsk2/ϩ mice develop autoantibodies to anti-Scl70 or anti-CENP-B is certainly similar to what has been reported for SSc, the fact that the mouse develops multiple autoantibodies to both of these Ags in 52 of the 60 Tsk2/ϩ plasma samples is a remarkable difference from what happens in humans (1,3,7,22). In addition, it is of great interest that this mouse also has autoimmune features similar to those reported for SLE, namely autoantibodies to dsDNA (46) and these autoantibodies to dsDNA are present predominantly in the same mice, which develop anti-Scl70 and/or anti-CENP-B Abs.…”

Section: Discussionmentioning

confidence: 99%

“…3 is an autoimmune disorder of unknown etiology and pathogenesis, characterized by the excessive accumulation of collagen and other extracellular matrix proteins in skin and various internal organs, prominent alterations in the microvasculature, and cellular and humoral immunological abnormalities including the development of multiple autoantibodies, some of which are disease-specific (1)(2)(3). The presence of anti-nuclear Abs (ANAs) is one of the most common manifestations of SSc, and Ͼ95% of SSc patients harbor ANAs (3,4).…”

Section: S Ystemic Sclerosis (Ssc)mentioning

confidence: 99%

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Demonstration of Autoimmunity in the Tight Skin-2 Mouse: A Model for Scleroderma

Gentiletti

McCloskey

Artlett

et al. 2005

The Journal of Immunology

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The tight skin-2 (Tsk2/+) mouse has been proposed as an animal model of systemic sclerosis (SSc) because this animal exhibits increased collagen synthesis and accumulation in the dermis. The Tsk2/+ mouse also has been reported to have a mononuclear cell infiltrate in the dermis; however, to date no evidence of autoimmunity has been described in this animal model. We report here that Tsk2/+ mice harbor numerous autoantibodies in their plasma including some, which are similar to those, present in SSc patients. Immunofluorescence with HEp-2 cells revealed the presence of anti-nuclear Abs (ANAs) in the plasma of 92% of the Tsk2/+ mice. In contrast, <5% of cage-mated CAST/ei mice had a positive ANA and none of the C3H/HeJ age-matched controls were positive. Homogenous, speckled, rim, nucleolar, centromere as well as combinations of these patterns were observed. The proportion of Tsk2/+ animals with a positive ANA increased slightly with age. ELISAs showed that 93% of the Tsk2/+ animals were positive for anti-Scl70, 82% for anti-centromere, 5% for anti-RNP/Sm, and none were positive for anti-RNA-polymerase II Abs. Indirect immunofluorescence with Crithidia luciliae and ELISA for anti-dsDNA Abs showed that 76% of Tsk2/+ mice were positive for this autoantibody. The high frequency of anti-Scl70 and anti-centromere autoantibodies indicates that Tsk2/+ mice display some humoral immune alterations which are similar to those found in patients with SSc. However, the Tsk2/+ mice also develop autoantibodies to dsDNA and a majority of the mice develop multiple autoantibody specificities (anti-Scl70, anti-CENP-B, and anti-dsDNA) indicating that the mouse may be a useful model to study autoimmunity in a wider spectrum of connective tissue diseases.

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“…Although, activated T lymphocytes elicit both type 1 (cell mediated) immune reaction and Type 2 (humoral) immune reaction, endothelium and extracellular matrix resulting in immune mediated tissue injury. 33 Basement membrane antigens, type 1 collagen, lymphocyte endothelial adhesion molecules, extracellular matrix by fibroblasts auto epitopes react with T lymphocytes, macrophages and mast cells via MHC class II complexes. This reaction aids in release of IL-4, IL-10, IL-13 and IL-17, TGF-ß that propagates the activation of fibroblasts, collagens, proteoglycans and fibronectin synthesis, inhibit the matrix metalloproteinase (involved in the degradation of collagen), produces IL-6 and PDGF and endothelial cell adhesion molecules like ICAM-1 and VCAM-1 in scleroderma.…”

Section: Psoriasismentioning

confidence: 99%

Autoimmune Disorders – Immunopathogenesis and Potential Therapies

Ganapathy¹,

Vedam²,

Rajeev³

et al. 2017

JYP

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Autoimmune disorders are formed in the body as an outcome of inappropriate immune response against its own tissues. Failure of this immune system to recognize the body's normal constituents as "self" will result in inflammation and tissue damage. Several immune based mechanisms form the basis of autoimmune disorders in the body. Management of these lesions is based on the diagnostic criteria, evaluation of clinical and oral manifestation, and laboratory investigations of these lesions. There is currently no definitive cure for all autoimmune disorders, although in rare cases they may disappear on their own. As patients experience temporary remissions in symptoms or progressive worsening, our pharmacological management are targeted only for symptomatic relief and arrest the progression of the lesion. A detailed approach to titles and abstracts of importance in this field on the topic of interest via review and case reports was included. This review article highlights on various immune pathogenic mechanisms and treatment modalities of autoimmune disorders.

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Antibodies in scleroderma: Direct pathogenicity and phenotypic associations

Cited by 58 publications

References 45 publications

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis

Autoimmunity to Vimentin Is Associated with Outcomes of Patients with Idiopathic Pulmonary Fibrosis

Demonstration of Autoimmunity in the Tight Skin-2 Mouse: A Model for Scleroderma

Autoimmune Disorders – Immunopathogenesis and Potential Therapies

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