Autoantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases.
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 gene 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 anti-fibrillin-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 Sjögren'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.
Tan
F K
FK
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas Health Science Center, Houston 77030, USA. tan@heart.med.uth.tmc.edu
Arnett
F C
FC
Antohi
S
S
Saito
S
S
Mirarchi
A
A
Spiera
H
H
Sasaki
T
T
Shoichi
O
O
Takeuchi
K
K
Pandey
J P
JP
Silver
R M
RM
LeRoy
C
C
Postlethwaite
A E
AE
Bona
C A
CA
D000328:Adult; D000918:Antibody Specificity; D044466:Asian People; D001323:Autoantibodies / Q000097:blood* / Q000737:chemistry; D044383:Black People; D017675:CREST Syndrome / Q000208:ethnology / Q000276:immunology; D003882:Dermatomyositis / Q000208:ethnology / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000276:immunology*; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D007198:Indians, North American; D008840:Microfilament Proteins / Q000276:immunology*; D008947:Mixed Connective Tissue Disease / Q000208:ethnology / Q000276:immunology; D012595:Scleroderma, Systemic / Q000208:ethnology / Q000276:immunology*; D044465:White People; D001741:Black or African American; D054392:Adipokines
D001323:Autoantibodies; D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse