Autoantibodies in systemic sclerosis and fibrosing syndromes: clinical indications and relevance

Cepeda, Eduardo J; Reveille, John D.

doi:10.1097/01.bor.0000144760.37777.fa

Cited by 88 publications

(86 citation statements)

References 105 publications

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“…As a control for antibody integrity, we compared levels of ANAs, ACAs, and anti-Scl-70 in the serum and in the purified immunoglobulins of patients with scleroderma (8). Results matched perfectly for most patients, indicating that the purification process did not significantly affect the autoantibody profile (data available online at www.…”

Section: Resultsmentioning

confidence: 99%

“…Scleroderma is an autoimmune disorder, as illustrated by the presence of autoantibodies against nuclei (ANAs), centromere (ACAs), topoisomerase I (Scl-70), endothelial cells, and many other self antigens (7,8). Some of these autoantibodies are useful diagnostic and prognostic markers, but whether they play a role in the pathogenesis of the disease is a matter of debate (7,8).…”

mentioning

confidence: 99%

“…Some of these autoantibodies are useful diagnostic and prognostic markers, but whether they play a role in the pathogenesis of the disease is a matter of debate (7,8).…”

mentioning

confidence: 99%

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Lack of evidence of stimulatory autoantibodies to platelet‐derived growth factor receptor in patients with systemic sclerosis

Classen¹,

Henrohn²,

Rorsman³

et al. 2009

Arthritis & Rheumatism

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Objective. Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology, characterized by fibrosis of the skin and multiple internal organs. Recent findings suggested that the disease is driven by stimulatory autoantibodies to platelet-derived growth factor receptor (PDGFR), which stimulate the production of reactive oxygen species (ROS) and collagen by fibroblasts. These results opened novel avenues of research into the diagnosis and treatment of SSc. The present study was undertaken to confirm the presence of anti-PDGFR antibodies in patients with SSc.Methods. Immunoglobulins from 37 patients with SSc were purified by protein A/G chromatography. PDGFR activation was tested using 4 different sensitive bioassays, i.e., cell proliferation, ROS production, signal transduction, and receptor phosphorylation; the latter was also tested in a separate population of 7 patients with SSc from a different research center.Results. Purified IgG samples from patients with SSc were positive when tested for antinuclear autoantibodies, but did not specifically activate PDGFR␣ or PDGFR␤ in any of the tests. Cell stimulation with PDGF itself consistently produced a strong signal.Conclusion. The present results raise questions regarding the existence of agonistic autoantibodies to PDGFR in SSc.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Lack of evidence of stimulatory autoantibodies to platelet‐derived growth factor receptor in patients with systemic sclerosis

Classen¹,

Henrohn²,

Rorsman³

et al. 2009

Arthritis & Rheumatism

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“…К настоящему времени описан и изучен ряд аутоантител, характерных для ССД и отличающих ее от других ревматических за-болеваний [12][13][14]. К основным специфичным для ССД относят антитела к топоизомеразе I (Scl-70), к РНК-полимеразе III и антицентромерные антитела (АЦА).…”

Section: новые классификационные критерии системной склеродермии (лекunclassified

Determinants of Morbidity and Mortality of Systemic Sclerosis in Canada

Al-Dhaher

Pope

Ouimet

2010

Seminars in Arthritis and Rheumatism

193

100

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“…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%

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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Autoantibodies in systemic sclerosis and fibrosing syndromes: clinical indications and relevance

Abstract: Autoantibodies in systemic sclerosis provide important and prognostic information and are useful in defining clinical subsets of the disease. When used appropriately, they can be a useful instrument in the management of scleroderma.

Cited by 88 publications

References 105 publications

Lack of evidence of stimulatory autoantibodies to platelet‐derived growth factor receptor in patients with systemic sclerosis

Lack of evidence of stimulatory autoantibodies to platelet‐derived growth factor receptor in patients with systemic sclerosis

Determinants of Morbidity and Mortality of Systemic Sclerosis in Canada

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

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