Systemic sclerosis (scleroderma): Specific autoantigen genes are selectively overexpressed in scleroderma fibroblasts

被引:54
作者
Zhou, XD
Tan, FK
Xiong, MM
Milewicz, DM
Feghali, CA
Fritzler, MJ
Reveille, JD
Arnett, FC
机构
[1] Univ Texas, Sch Med, Div Rheumatol & Clin Immunogenet, Houston, TX 77030 USA
[2] Univ Texas, Sch Med, Div Med Genet, Dept Internal Med, Houston, TX 77030 USA
[3] Univ Texas, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA
[4] Univ Pittsburgh, Dept Med, Div Clin Immunol & Rheumatol, Pittsburgh, PA 15261 USA
[5] Univ Calgary, Fac Med, Calgary, AB, Canada
关键词
D O I
10.4049/jimmunol.167.12.7126
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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收藏
页码:7126 / 7133
页数:8
相关论文
共 31 条
  • [1] PRELIMINARY CRITERIA FOR THE CLASSIFICATION OF SYSTEMIC-SCLEROSIS (SCLERODERMA)
    不详
    [J]. ARTHRITIS AND RHEUMATISM, 1980, 23 (05): : 581 - 590
  • [2] Arnett F C, 1995, Int Rev Immunol, V12, P107, DOI 10.3109/08830189509056707
  • [3] Increased prevalence of systemic sclerosis in a native American tribe in Oklahoma - Association with an Amerindian HLA haplotype
    Arnett, FC
    Howard, RF
    Tan, FM
    Moulds, JM
    Bias, WB
    Durban, E
    Cameron, HD
    Paxton, G
    Hodge, TJ
    Weathers, PE
    Reveille, JD
    [J]. ARTHRITIS AND RHEUMATISM, 1996, 39 (08): : 1362 - 1370
  • [4] Autoantibodies to fibrillarin in systemic sclerosis (scleroderma) - An immunogenetic, serologic, and clinical analysis
    Arnett, FC
    Reveille, JD
    Goldstein, R
    Pollard, KM
    Leaird, K
    Smith, EA
    Leroy, EC
    Fritzler, MJ
    [J]. ARTHRITIS AND RHEUMATISM, 1996, 39 (07): : 1151 - 1160
  • [5] Bunn CC, 1999, CLIN EXP IMMUNOL, V117, P207
  • [6] Scleroderma autoantigens are uniquely fragmented by metal-catalyzed oxidation reactions: Implications for pathogenesis
    CasciolaRosen, L
    Wigley, F
    Rosen, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (01) : 71 - 79
  • [7] Is anti-topoisomerase I a serum marker of pulmonary involvement in systemic sclerosis?
    Diot, E
    Giraudeau, B
    Diot, P
    Degenne, D
    Ritz, L
    Guilmot, JL
    Lemarié, E
    [J]. CHEST, 1999, 116 (03) : 715 - 720
  • [8] 3 HUMAN CHROMOSOMAL AUTOANTIGENS ARE RECOGNIZED BY SERA FROM PATIENTS WITH ANTICENTROMERE ANTIBODIES
    EARNSHAW, W
    BORDWELL, B
    MARINO, C
    ROTHFIELD, N
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1986, 77 (02) : 426 - 430
  • [9] Cluster analysis and display of genome-wide expression patterns
    Eisen, MB
    Spellman, PT
    Brown, PO
    Botstein, D
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) : 14863 - 14868
  • [10] Fanning GC, 1998, BRIT J RHEUMATOL, V37, P201