Influence of ethnic background on clinical and serologic features in patients with systemic sclerosis and anti-DNA topoisomerase I antibody

Kuwana, Masataka; Kaburaki, Junichi; Arnett, Frank C.; Howard, Robert F.; Medsger, Thomas A.; Wright, Timothy M.

doi:10.1002/1529-0131(199904)42:3<465::aid-anr11>3.0.co;2-y

Cited by 128 publications

(101 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consequently, SSc survival studies from Canada, Hungary, Spain, England, Japan, Denmark, Sweden, Australia, Italy and Greece show a wide variation in outcomes. [2][3][4][5][6][7] Our study compares the survival of patients with scleroderma seen at the same institution by the same investigators over a 30-year time period. All patients were evaluated and were followed up in a similar fashion, making it possible to compare time periods.…”

Section: Discussionmentioning

confidence: 99%

Changes in causes of death in systemic sclerosis, 1972-2002

Steen

Medsger

2007

Annals of the Rheumatic Diseases

1,359

869

View full text Add to dashboard Cite

Background: Survival of scleroderma has changed since the renal crisis treatment has become possible. Aims: To document the changes in survival and organ system causes of mortality in systemic sclerosis (SSc) over the past 25 years in patients from a single medical centre. Methods: Consecutive patients evaluated at the University of Pittsburgh, Pittsburgh, Pennsylvania, USA between 1 January 1972 and 31 December 1996 were studied. Survival was determined in five 5-year time periods between 1972 and 1997. Causes of death included scleroderma-related (scleroderma renal crisis, pulmonary arterial hypertension, pulmonary fibrosis (PF), gastrointestinal (GI), heart and multiorgan failure) and non-scleroderma-related (cancer, atherosclerotic cardiovascular or cerebrovascular disease, infection, sudden death, other and unknown) causes. Results: The 10-year survival improved steadily from 54% to 66% during each of the time intervals. There was a significant improvement in survival for patients during 1982-91 compared with those during 1972-81 (p,0.001), even when patients with renal crisis were excluded (p,0.005). The frequency of deaths due to renal crisis significantly decreased over the 30-year time period, from 42% to 6% of scleroderma-related deaths (p,0.001), whereas the proportion of patients with scleroderma who died of PF increased from 6% to 33% (p,0.001). The frequency of pulmonary hypertension, independent of PF, also significantly increased during this time period (p,0.05). There were no changes in scleroderma GI-and heart-related deaths, nor in any of the non-scleroderma-related causes, although patients with scleroderma were less likely to die from scleroderma-related problems in the past 15 years. Conclusion: The change in the pattern of scleroderma-related deaths over the past 30 years demonstrates that the lung (both pulmonary hypertension and PF) is the primary cause of scleroderma-related deaths today. It is important that aggressive searches continue to develop better therapies for these severe pulmonary complications of SSc.

show abstract

Section: Discussionmentioning

confidence: 99%

Changes in causes of death in systemic sclerosis, 1972-2002

Steen

Medsger

2007

Annals of the Rheumatic Diseases

1,359

869

View full text Add to dashboard Cite

show abstract

“…It consists of several polypeptides, of which two proteins of 75 and 100 kDa have been identified as the major antigenic components. Anti-PM-Scl Abs occur almost exclusively in a small percentage of Caucasians with SSc, myositis, or both (21).…”

Section: Discussionmentioning

confidence: 99%

Systemic Sclerosis (Scleroderma): Specific Autoantigen Genes Are Selectively Overexpressed in Scleroderma Fibroblasts

Zhou

Tan

Xiong

et al. 2001

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

The pathogenesis of systemic sclerosis (SSc) involves complex interactions between activated fibroblasts eventually leading to fibrosis, and impaired immune tolerance characterized by a variety of circulating SSc-specific autoantibodies. The expression of autoantigens in fibroblasts, a key target tissue in SSc, may play an important role in this process. To obtain a global view of this process, we examined gene expression profiles of SSc dermal fibroblasts using cDNA microarrays. The results show that dermal fibroblasts from SSc patients obtained from either affected or unaffected skin displayed a characteristic pattern of increased SSc autoantigen gene expression compared with that from normal controls. In particular, fibrillarin (p = 0.028), centromeric protein B (p = 0.01), centromeric autoantigen P27 (p = 0.042), and RNA polymerase II (220 kDa; p = 0.02) were significantly overexpressed in SSc fibroblasts. Quantitative RT-PCR confirmed overexpression of these autoantigens and also revealed increased levels of DNA topoisomerase I transcripts in SSc fibroblasts compared with normal control fibroblasts (p = 0.0318). The polymyositis/scleroderma autoantigen gene was overexpressed in some SSc patients (p = 0.09). To examine the specificity of these overexpressed autoantigen genes for SSc and its tissue specificity for fibroblasts, cDNA microarrays of dermal fibroblasts from patients with eosinophilic fasciitis and scleromyxedema were studied as well as PBMC and muscle biopsies from SSc patients. None of these tissues showed significant alterations in gene expression of SSc-specific autoantigens. Therefore, SSc-associated autoantigen genes are selectively overexpressed in SSc dermal fibroblasts, a major tissue involved in disease pathogenesis.

show abstract

“…The definitions used to determine organ involvement, including involvement of the peripheral vasculature (digital ulcers and/or gangrene), joint, esophagus, small intestine, lung (pulmonary interstitial fibrosis and isolated pulmonary arterial hypertension), heart, kidney (renal crisis), and muscle, have been described previously (4,14). End-stage lung disease was defined as forced vital capacity Ͻ50% of predicted and/or lung-related death (15).…”

Section: Methodsmentioning

confidence: 99%

Enzyme‐linked immunosorbent assay for detection of Anti–RNA polymerase III antibody: Analytical accuracy and clinical associations in systemic sclerosis

Kuwana

Okano

Pandey

et al. 2005

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Objective. We have recently developed an enzymelinked immunosorbent assay (ELISA) for detection of anti-RNA polymerase III (anti-RNAP III) antibody, using a recombinant fragment containing the immunodominant epitope as the antigen source. This study was conducted to assess the analytical accuracy and clinical associations of the anti-RNAP III ELISA in patients with systemic sclerosis (SSc).Methods. To evaluate analytical sensitivity and specificity of the ELISA, both immunoprecipitation tests and ELISA were used to detect anti-RNAP III antibody in 534 SSc sera from patients at 3 medical centers. Sera from 522 SSc patients and 516 controls, including patients with other connective tissue diseases and blood bank donors, were also evaluated to assess the clinical sensitivity and specificity of the ELISA. Clinical findings in anti-RNAP III antibody-positive SSc patients were compared between patient groups stratified according to anti-RNAP III antibody levels determined by the ELISA.Results. In SSc patients, our ELISA showed analytical sensitivity of 91% and analytical specificity of 99% compared with the immunoprecipitation assay (a gold standard for detection of anti-RNAP III antibody). The additional analysis using a large series of SSc and control sera showed that clinical sensitivity and specificity of the ELISA with respect to the diagnosis of SSc were 17% and 98%, respectively. A high level of anti-RNAP III antibody was associated with diffuse cutaneous SSc, higher maximum total skin score, and increased frequency of tendon friction rubs.Conclusion. The anti-RNAP III ELISA is analytically accurate and clinically specific. With this assay, testing for anti-RNAP III antibody can be made routinely available.

show abstract

Influence of ethnic background on clinical and serologic features in patients with systemic sclerosis and anti-DNA topoisomerase I antibody

Cited by 128 publications

References 41 publications

Changes in causes of death in systemic sclerosis, 1972-2002

Changes in causes of death in systemic sclerosis, 1972-2002

Systemic Sclerosis (Scleroderma): Specific Autoantigen Genes Are Selectively Overexpressed in Scleroderma Fibroblasts

Enzyme‐linked immunosorbent assay for detection of Anti–RNA polymerase III antibody: Analytical accuracy and clinical associations in systemic sclerosis

Contact Info

Product

Resources

About