Antiantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases

Filemon K. Tan, Frank C. Arnett, Stephan Antohi, Shinichiro Saito, Adriana Mirarchi, Harry Spiera, Takeshi Sasaki, Ozaki Shoichi, Ken Takeuchi, Janadan P. Pandy, Richard M. Silver, Carwile LeRoy, Arnold Postlethwaite, Constantin A. Bona

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

A duplication in the fibrillin-1 gene has been implicated as the cause of the tight skin 1 (tsk1) phenotype, an animal model of scleroderma or systemic sclerosis (SSc). In addition to the production of abnormal fibrillin-1 protein, the tsk1 mouse also produces autoantibodies to fibrillin-1. Among a population of Choctaw Native Americans with the highest prevalence of SSc yet described, a chromosome 15q haplotype containing the fibrillin-1 gone has been strongly associated with SSc. With a recombinant human fibrillin-1 protein, autoantibodies to fibrillin-1 were detected in the sera of Native American SSc patients that correlated significantly with disease. Abs to fibrillin-1 also were detected in sera from Japanese, Caucasian, and African-American SSc patients. Compared with other ethnic groups, Japanese and Native American SSc patients had significantly higher frequencies of antifibrillin-1 Abs. Sera from patients with diffuse SSc, calcinosis, Raynaud's, esophageal dysmotility, sclerodactyly, and telangiectasias syndrome and mixed connective tissue disease also had significantly higher frequencies of anti-fibrillin-1 Abs than sera from controls or patients with other non-SSc connective tissue diseases (lupus, rheumatoid arthritis, and Sjogren's syndrome). Ab specificity for fibrillin- 1 was demonstrated by the lack of binding to a panel of other purified autoantigens. The results presented demonstrate for the first time the presence of high levels of anti-fibrillin-1 Abs in a significant portion of patients with SSc.

Original languageEnglish (US)
Pages (from-to)1066-1072
Number of pages7
JournalJournal of Immunology
Volume163
Issue number2
StatePublished - Jul 15 1999

Fingerprint

Connective Tissue Diseases
Extracellular Matrix Proteins
Systemic Scleroderma
North American Indians
Serum
Autoantibodies
Esophageal Motility Disorders
Mixed Connective Tissue Disease
Fibrillin-1
microfibrillar protein
Calcinosis
Diffuse Scleroderma
Telangiectasis
Skin
Asian Americans
Sjogren's Syndrome
Autoantigens
Sclerosis
Ethnic Groups
African Americans

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Tan, F. K., Arnett, F. C., Antohi, S., Saito, S., Mirarchi, A., Spiera, H., ... Bona, C. A. (1999). Antiantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases. Journal of Immunology, 163(2), 1066-1072.

Antiantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases. / Tan, Filemon K.; Arnett, Frank C.; Antohi, Stephan; Saito, Shinichiro; Mirarchi, Adriana; Spiera, Harry; Sasaki, Takeshi; Shoichi, Ozaki; Takeuchi, Ken; Pandy, Janadan P.; Silver, Richard M.; LeRoy, Carwile; Postlethwaite, Arnold; Bona, Constantin A.

In: Journal of Immunology, Vol. 163, No. 2, 15.07.1999, p. 1066-1072.

Research output: Contribution to journalArticle

Tan, FK, Arnett, FC, Antohi, S, Saito, S, Mirarchi, A, Spiera, H, Sasaki, T, Shoichi, O, Takeuchi, K, Pandy, JP, Silver, RM, LeRoy, C, Postlethwaite, A & Bona, CA 1999, 'Antiantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases', Journal of Immunology, vol. 163, no. 2, pp. 1066-1072.
Tan, Filemon K. ; Arnett, Frank C. ; Antohi, Stephan ; Saito, Shinichiro ; Mirarchi, Adriana ; Spiera, Harry ; Sasaki, Takeshi ; Shoichi, Ozaki ; Takeuchi, Ken ; Pandy, Janadan P. ; Silver, Richard M. ; LeRoy, Carwile ; Postlethwaite, Arnold ; Bona, Constantin A. / Antiantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases. In: Journal of Immunology. 1999 ; Vol. 163, No. 2. pp. 1066-1072.
@article{5945e4eabf94428591c1ade8f6a12523,
title = "Antiantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases",
abstract = "A duplication in the fibrillin-1 gene has been implicated as the cause of the tight skin 1 (tsk1) phenotype, an animal model of scleroderma or systemic sclerosis (SSc). In addition to the production of abnormal fibrillin-1 protein, the tsk1 mouse also produces autoantibodies to fibrillin-1. Among a population of Choctaw Native Americans with the highest prevalence of SSc yet described, a chromosome 15q haplotype containing the fibrillin-1 gone has been strongly associated with SSc. With a recombinant human fibrillin-1 protein, autoantibodies to fibrillin-1 were detected in the sera of Native American SSc patients that correlated significantly with disease. Abs to fibrillin-1 also were detected in sera from Japanese, Caucasian, and African-American SSc patients. Compared with other ethnic groups, Japanese and Native American SSc patients had significantly higher frequencies of antifibrillin-1 Abs. Sera from patients with diffuse SSc, calcinosis, Raynaud's, esophageal dysmotility, sclerodactyly, and telangiectasias syndrome and mixed connective tissue disease also had significantly higher frequencies of anti-fibrillin-1 Abs than sera from controls or patients with other non-SSc connective tissue diseases (lupus, rheumatoid arthritis, and Sjogren's syndrome). Ab specificity for fibrillin- 1 was demonstrated by the lack of binding to a panel of other purified autoantigens. The results presented demonstrate for the first time the presence of high levels of anti-fibrillin-1 Abs in a significant portion of patients with SSc.",
author = "Tan, {Filemon K.} and Arnett, {Frank C.} and Stephan Antohi and Shinichiro Saito and Adriana Mirarchi and Harry Spiera and Takeshi Sasaki and Ozaki Shoichi and Ken Takeuchi and Pandy, {Janadan P.} and Silver, {Richard M.} and Carwile LeRoy and Arnold Postlethwaite and Bona, {Constantin A.}",
year = "1999",
month = "7",
day = "15",
language = "English (US)",
volume = "163",
pages = "1066--1072",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Antiantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases

AU - Tan, Filemon K.

AU - Arnett, Frank C.

AU - Antohi, Stephan

AU - Saito, Shinichiro

AU - Mirarchi, Adriana

AU - Spiera, Harry

AU - Sasaki, Takeshi

AU - Shoichi, Ozaki

AU - Takeuchi, Ken

AU - Pandy, Janadan P.

AU - Silver, Richard M.

AU - LeRoy, Carwile

AU - Postlethwaite, Arnold

AU - Bona, Constantin A.

PY - 1999/7/15

Y1 - 1999/7/15

N2 - A duplication in the fibrillin-1 gene has been implicated as the cause of the tight skin 1 (tsk1) phenotype, an animal model of scleroderma or systemic sclerosis (SSc). In addition to the production of abnormal fibrillin-1 protein, the tsk1 mouse also produces autoantibodies to fibrillin-1. Among a population of Choctaw Native Americans with the highest prevalence of SSc yet described, a chromosome 15q haplotype containing the fibrillin-1 gone has been strongly associated with SSc. With a recombinant human fibrillin-1 protein, autoantibodies to fibrillin-1 were detected in the sera of Native American SSc patients that correlated significantly with disease. Abs to fibrillin-1 also were detected in sera from Japanese, Caucasian, and African-American SSc patients. Compared with other ethnic groups, Japanese and Native American SSc patients had significantly higher frequencies of antifibrillin-1 Abs. Sera from patients with diffuse SSc, calcinosis, Raynaud's, esophageal dysmotility, sclerodactyly, and telangiectasias syndrome and mixed connective tissue disease also had significantly higher frequencies of anti-fibrillin-1 Abs than sera from controls or patients with other non-SSc connective tissue diseases (lupus, rheumatoid arthritis, and Sjogren's syndrome). Ab specificity for fibrillin- 1 was demonstrated by the lack of binding to a panel of other purified autoantigens. The results presented demonstrate for the first time the presence of high levels of anti-fibrillin-1 Abs in a significant portion of patients with SSc.

AB - A duplication in the fibrillin-1 gene has been implicated as the cause of the tight skin 1 (tsk1) phenotype, an animal model of scleroderma or systemic sclerosis (SSc). In addition to the production of abnormal fibrillin-1 protein, the tsk1 mouse also produces autoantibodies to fibrillin-1. Among a population of Choctaw Native Americans with the highest prevalence of SSc yet described, a chromosome 15q haplotype containing the fibrillin-1 gone has been strongly associated with SSc. With a recombinant human fibrillin-1 protein, autoantibodies to fibrillin-1 were detected in the sera of Native American SSc patients that correlated significantly with disease. Abs to fibrillin-1 also were detected in sera from Japanese, Caucasian, and African-American SSc patients. Compared with other ethnic groups, Japanese and Native American SSc patients had significantly higher frequencies of antifibrillin-1 Abs. Sera from patients with diffuse SSc, calcinosis, Raynaud's, esophageal dysmotility, sclerodactyly, and telangiectasias syndrome and mixed connective tissue disease also had significantly higher frequencies of anti-fibrillin-1 Abs than sera from controls or patients with other non-SSc connective tissue diseases (lupus, rheumatoid arthritis, and Sjogren's syndrome). Ab specificity for fibrillin- 1 was demonstrated by the lack of binding to a panel of other purified autoantigens. The results presented demonstrate for the first time the presence of high levels of anti-fibrillin-1 Abs in a significant portion of patients with SSc.

UR - http://www.scopus.com/inward/record.url?scp=0033564969&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033564969&partnerID=8YFLogxK

M3 - Article

VL - 163

SP - 1066

EP - 1072

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -