|
1. |
The Role of the Trimolecular Complex (αβTCR-MHC+Peptide) in the Pathogenesis of Systemic Sclerosis |
|
International Reviews of Immunology,
Volume 12,
Issue 2-4,
1995,
Page 85-96
DwyerEdward,
WinchesterRobert,
Preview
|
PDF (852KB)
|
|
ISSN:0883-0185
DOI:10.3109/08830189509056705
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
|
2. |
T Cell Repertoire in Systemic Sclerosis |
|
International Reviews of Immunology,
Volume 12,
Issue 2-4,
1995,
Page 97-105
YurovskyVladimir V.,
WhiteBarbara,
Preview
|
PDF (624KB)
|
|
摘要:
An increase of certain T cell subsets in systemic sclerosis patients, particularly of V81+γδT cells in the blood and lungs and CD8+αβT cells in the lungs, has been shown. The diversity of T cell antigen receptor (TCR) Vδ1, Vα, and Vβgene repertoires was examined using reverse transcriptase-polymerase chain reaction to amplify rearranged TCR transcripts across the junctional region. This was followed by two methods of analysis. First, the relative expression of Vαand Vβgenes was determined in the blood and bronchoalveolar lavage fluid of the patients. Second, we looked for evidence of restricted diversity of the junctional regions in TCR Vδ1 transcripts and in different Vαand Vβgene families. Limited Vδ1-Cδjunctional region lengths were observed in the patients compared to controls. This was confirmed by sequence analysis of Vδ1-Cδjunctional regions after subcloning amplified products in a bacterial vector. A restricted diversity of the junctional region lengths was also detected in a number of Vαand Vβgene families, particularly within bronchoalveolar CD8+T cell subset. These data suggest that the oligoclonal expansion of the correspondingαβandγδT cells is antigen-driven and may be important in the pathogenesis of systemic sclerosis.
ISSN:0883-0185
DOI:10.3109/08830189509056706
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
|
3. |
HLA and Autoimmunity in Scleroderma (Systemic Sclerosis) |
|
International Reviews of Immunology,
Volume 12,
Issue 2-4,
1995,
Page 107-128
ArnettFrank C.,
Preview
|
PDF (1346KB)
|
|
摘要:
Scleroderma or systemic sclerosis (SSc) has been associated with certain class II antigens of the major histocompatibility complex (MHC), including HLA-DR1, DR2, DR3, DR5, and DR52. In general, these earlier HLA correlations were weak and varied considerably among reporting centers and different ethnic populations. More recently, a variety of disease-specific autoantibodies have been discovered including anticentromere, anti-topoisomerase I, and a variety of anti-nucleolar antibodies. These specificities show little overlap among one another, and each are markers for certain clinical features of SSc.At the same time, molecular studies of the MHC have provided more accurate methods for defining specific HLA alleles. Now it is becoming clear that certain HLA class II alleles, especially HLA-DQ, are more strongly associated with autoantibody subsets of SSc than with the disease itself. For example, anticentromere antibodies are strongly associated with HLA-DQB1*0501 (DQ5), DQB1*0301 (DQ7) and other DQB1 alleles possessing a glycine or tyrosine residue in position 26 of the outermost domain. Anti-topoisomerase I antibodies occur in SSc patients with HLA-DQB1*0301 (DQ7), DQB1*0302 (DQ8), DQB1*0601 (DQ6 in Japanese), and other DQB1 alleles possessing a tyrosine residue in position 30. HLA-DQ alleles associated with these autoantibodies tend to be in linkage disequilibrium with the HLA-DR specificities previously associated weakly with SSc itself. Rare multiplex families with SSc also show these same HLA haplotypes co-segregating with autoantibody profiles in affected members. Thus, it appears that MHC alleles play a role in affecting the serological expression of SSc, and the implications of these recent findings are discussed.
ISSN:0883-0185
DOI:10.3109/08830189509056707
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
|
4. |
Molecular Structure and Function of Autoantigens in Systemic Sclerosis |
|
International Reviews of Immunology,
Volume 12,
Issue 2-4,
1995,
Page 129-144
LeeBenhur,
CraftJoseph E.,
Preview
|
PDF (1149KB)
|
|
ISSN:0883-0185
DOI:10.3109/08830189509056708
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
|
5. |
Autoantibodies in Systemic Sclerosis |
|
International Reviews of Immunology,
Volume 12,
Issue 2-4,
1995,
Page 145-157
VázquezDolores,
RothfieldNaomi F.,
Preview
|
PDF (794KB)
|
|
摘要:
There are 3 major autoantibodies in sera from patients with scleroderma: 1) anticentromere antibodies (ACA), 2) anti-topoisomerase I (anti-topo I), and 3) anti-RNA polymerases. Each is present in about 25% of patients and are mutually exclusive. ACA are found in patients with primary and secondary Raynaud's disease and in patients with primary biliary cirrhosis. Anti-topo 1 and anti-RNA polymerases are found exclusively in scleroderma. Each autoantibody is present in specific subsets of scleroderma patients. ACA and anti-topo I have been well studied and their presence and liter are stable over time. The anti-topo I and ACA are of all three isotypes, recognize multiple epitopes on the antigens and have stable cross reactive or private idiotypes. The antigen, topoisomerase I, has domains which have homology to viral proteins. Other autoantibodies predominantly recognize nucleolar antigens, are found in less than 15% of patients, and are not specific for scleroderma.
ISSN:0883-0185
DOI:10.3109/08830189509056709
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
|
6. |
Retroviruses and the Pathogenesis of Systemic Sclerosis |
|
International Reviews of Immunology,
Volume 12,
Issue 2-4,
1995,
Page 159-175
JimenezSergio A.,
DiazArturo,
KhaliliKamel,
Preview
|
PDF (1201KB)
|
|
ISSN:0883-0185
DOI:10.3109/08830189509056710
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
|
7. |
Regulation of Type I Collagen Genes Expression |
|
International Reviews of Immunology,
Volume 12,
Issue 2-4,
1995,
Page 177-185
KarsentyGerard,
WoonRang,
Preview
|
PDF (582KB)
|
|
摘要:
Type I collagen, the most abundant protein of the body, is preferentially synthesized in bone, dermis, and tendons by two cell types, the osteoblast and the fibroblast. The expression of type I collagen is increased in the various forms of fibrosis such as lung, liver, bone marrow fibrosis and scleroderma. Type I collagen is a helerotrimer molecule consisting of twoα1(I) chains and oneα2(I) chain. The two polypeptide chains are synthesized in a 2:1 stoichiometry. The same 2:1 ratio is observed for the rate of synthesis of the corresponding mRNAs. One hypothesis that would explain how this coregulation occurs at the transcriptional level is that common cis-acting elements are present on both genes. These common regulatory elements would bind identical transcription factors displaying the same function. The characterization of the various regulatory elements present in these genes would foster our understanding of the molecular mechanisms controlling type I collagen gene expression in normal and in pathological situations.Over the past few years, several laboratories have identified cis-acting elements in the promoters of the COL1 Al and COL1A2 genes. At least, two of these cis-acting elements are common to both promoters. One is centered by a pentanucleotide CCAAT and binds a ubiquitously expressed heteromeric CCAAT binding factor. A second one is centered by a G-rich region and it binds a new transcription factor called c-Krox. Interestingly, the c-Krox gene, whose expression is regulated by growth factors, is preferentially expressed in skin fibroblasts in mice and is absent in bone suggesting that it plays a role in the fibroblast specific expression of type I collagen genes. The knowledge of how this and eventually other transcription factors act to regulate collagen expression will eventually lead to a better understanding of the increased type I collagen gene expression seen in diseases such as scleroderma.
ISSN:0883-0185
DOI:10.3109/08830189509056711
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
|
8. |
Regulation of Connective Tissue Synthesis in Systemic Sclerosis |
|
International Reviews of Immunology,
Volume 12,
Issue 2-4,
1995,
Page 187-199
VargaJohn,
BasheyReza I.,
Preview
|
PDF (958KB)
|
|
摘要:
Excessive connective tissue deposition in the skin and other organs is the pathologic hallmark of systemic sclerosis (SSc), and fibrosis accounts for much of the chronic morbidity of this disease. Unregulated production of collagen in SSc skin fibroblasts has been demonstrated both in vivo and in vitro, and is considered to be a critical process in the development of fibrosis. In addition to collagen, other components of the extracellular matrix are also overexpressed in SSc fibroblasts, and may be important in the functional alterations of connective tissue. The transcriptional activity of several genes coding for matrix macromolecules is upregulated in SSc fibroblasts. The pleiotropic signaling molecule transforming growth factor-β(TGFβ) is likely to be intimately involved in initiating and perhaps perpetuating the fibrotic response in SSc. TGFβ, a potent profibrotic cytokine, is highly expressed in endothelial cells, in fibroblasts near blood vessels, and in perivascular inflammatory cells in involved tissues in SSc. The apparent failure of SSc fibroblasts to down-regulate their collagen synthesis when cultured in a three-dimensional matrix suggest an additional mechanism for the maintenance of unregulated collagen production in these cells. Finally, subpopulations of fibroblasts with an activated biosynthetic phenotype may become dominant in SSc. Therefore, persistent elevation of extracellular matrix gene expression in SSc tissues may be the result of a series of events representing the interaction of genetic and hormonal factors. A precise delineation of the mechanisms of fibroblast activation is needed for understanding the pathogenesis of SSc, and for the rational design of therapeutic interventions aimed at interfering with the fibrotic process.
ISSN:0883-0185
DOI:10.3109/08830189509056712
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
|
9. |
Animal Models of Scleroderma: Contrasts and Comparisons |
|
International Reviews of Immunology,
Volume 12,
Issue 2-4,
1995,
Page 201-216
Van de WaterJudy,
JimenezSergio A.,
GershwinM. Eric,
Preview
|
PDF (1507KB)
|
|
ISSN:0883-0185
DOI:10.3109/08830189509056713
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
|
10. |
Adhesion Molecules in Scleroderma: Collagen Binding Integrins |
|
International Reviews of Immunology,
Volume 12,
Issue 2-4,
1995,
Page 217-225
KupperThomas S.,
Preview
|
PDF (741KB)
|
|
ISSN:0883-0185
DOI:10.3109/08830189509056714
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
|
|