Immunobiology of systemic sclerosisThe Immunobiology of Systemic Sclerosis
Section snippets
Methods
We performed a PubMed search using the terms “systemic sclerosis” in the period of 1989 to 2007, restricted to the English Language. This yielded a total of 9099 publications, including 1252 reviews. From this list and based on the abstracts, a total of 328 articles were initially chosen that appeared to highlight recent progress in the pathogenesis of SSc as well as in the use of diagnostic tools and therapeutic approaches. A final review of the data in 262 articles regarding the current
Discussion
Recent human studies, animal models, and gene analyses have provided much deeper insight into the molecular mechanisms behind the development of SSc. In review of these collective data, the hallmarks of vascular damage, immunologic activation, and collagen deposition can be traced to 4 major factors: T-cells, fibroblasts, B-cells, and cytokines/chemokines.
T-cells are the major component of the infiltrate in both the lung and the skin of SSc patients, frequently exhibit an activated phenotype,
References (262)
- et al.
Expression of intercellular adhesion molecule-1 (ICAM-1) in the skin of patients with systemic scleroderma
J Invest Dermatol
(1991) - et al.
Circulating intercellular adhesion molecule-1 in patients with systemic sclerosis
Clin Immunol Immunopathol
(1993) - et al.
Fibroblasts in mechanically stressed collagen lattices assume a “synthetic” phenotype
J Biol Chem
(2001) - et al.
Interstitial lung disease in systemic sclerosis: comparison of BALF lymphocyte phenotype and DLCO impairment
Respir Med
(1998) - et al.
Immunoregulation of autoimmunity by natural killer T-cells
Hum Immunol
(2005) - et al.
Emerging role of γδ T-cells in health and disease
Blood Rev
(2002) - et al.
γδ receptor bearing T-cells in scleroderma: enhanced interaction with vascular endothelial cells in vitro
Clin Immunol
(1999) - et al.
T-cell lines from systemic sclerosis patients and healthy controls recognize multiple epitopes on DNA topoisomerase I
J Autoimmun
(2006) - et al.
Skewing of the CD8+ T-cell repertoire in the lungs of patients with systemic sclerosis
Hum Immunol
(1996) - et al.
Increased expression of CD40 ligand in activated CD4+ T-lymphocytes of systemic sclerosis patients
J Autoimmun
(2000)
Function blocking autoantibodies against matrix metalloproteinase-1 in patients with systemic sclerosis
J Invest Dermatol
Platelet-derived growth factor and reactive oxygen species (ROS) regulate Ras protein levels in primary human fibroblasts via ERK1/2Amplification of ROS and Ras in systemic sclerosis fibroblasts
J Biol Chem
Anti-endothelial cell antibodies from patients with limited cutaneous systemic sclerosis bind to centromeric protein B (CENP-B)
Clin Immunol
Endothelial injury in internal organs of University of California at Davis line 200 (UCD 200) chickens, an animal model for systemic sclerosis (Scleroderma)
J Autoimmun
B Lymphocyte signaling established by the CD19/CD22 loop regulates autoimmunity in the tight-skin mouse
Am J Pathol
B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis
Am J Pathol
B-cell deficiency does not abrogate development of cutaneous hyperplasia in mice inheriting the defective fibrillin-1 gene
J Autoimmun
Distinct immune profiles characterize patients with diffuse or limited systemic sclerosis
Clin Immunol
Murine animal models of systemic sclerosis
Curr Opin Rheumatol
Animal models of scleroderma: contrasts and comparisons
Int Rev Immunol
Sequential dermal microvascular and perivascular changes in the development of scleroderma
J Pathol
Endothelial cell apoptosis in systemic sclerosis is induced by antibody-dependent cell-mediated cytotoxicity via CD95
Arthritis Rheum
Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma
J Clin Invest
Early T-cell activation in the skin from patients with systemic sclerosis
Ann Rheum Dis
Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis
Am J Pathol
Circulating Vδ1+ T-cells are activated and accumulate in the skin of systemic sclerosis patients
Arthritis Rheum
Mononuclear cellular infiltrates in clinically involved skin from patients with systemic sclerosis of recent onset predominantly consist of monocytes/macrophages
Pathobiology
Dermal mast cell degranulation in systemic sclerosis
Arthritis Rheum
The roles of transforming growth factor type β3 (TGF-β3) and mast cells in the pathogenesis of scleroderma
Clin Rheumatol
Endothelial and fibroblastic activation in sclerodermaThe myth of the “uninvolved skin”
Arthritis Rheum
In situ expression of cytokines and cellular adhesion molecules in the skin of patients with systemic sclerosisTheir role in early and late disease
Pathobiology
Up-regulation of class II major histocompatibility complex and intercellular adhesion molecule 1 expression on scleroderma fibroblasts and endothelial cells by interferon-γ and tumor necrosis factor α in the early disease stage
Arthritis Rheum
α4β1 and α4β7 CD4+ T-cell numbers increase and CLA+ CD4+ T-cell numbers decrease in systemic sclerosis
Clin Exp Immunol
Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients
Rheumatology (Oxford)
Circulating intercellular adhesion molecule-1 in the sera of patients with systemic sclerosis: enhancement by inflammatory cytokines
Br J Rheumatol
Localization of collagen mRNA in normal and scleroderma skin by in-situ hybridization
Eur J Clin Invest
Systemic and cell type-specific gene expression patterns in scleroderma skin
Proc Natl Acad Sci USA
Expression of pro-inflammatory markers by human dermal fibroblasts in a three-dimensional culture model is mediated by an autocrine interleukin-1 loop
Biochem J
Structural features of interstitial lung disease in systemic sclerosis
Am Rev Respir Dis
Fibrosing alveolitis in systemic sclerosis: increase in memory T-cells in lung interstitium
Eur Respir J
Alterations of mononuclear inflammatory cellsCD4/CD8+ T-cells, interleukin 1β, and tumour necrosis factor α in the bronchoalveolar lavage fluid, peripheral blood, and skin of patients with systemic sclerosis
J Clin Pathol
Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T-cells from scleroderma patients
Arthritis Rheum
Derangement of apoptosis-related lymphocyte homeostasis in systemic sclerosis
Rheumatology (Oxford)
Analysis of lymphocyte subpopulations in systemic sclerosis
J Investig Allergol Clin Immunol
Reduced circulating natural killer T-cells and γ/δ T-cells in patients with systemic sclerosis
J Rheumatol
Natural killer cells and γδ T-cells in scleroderma: relationship to disease duration and anti-Scl-70 antibodies
Ann Rheum Dis
Dysfunction of T-cell receptor AV24AJ18+BV11+ double-negative regulatory natural killer T-cells in autoimmune diseases
Arthritis Rheum
Decreased CD161+CD8+T-cells in the peripheral blood of patients suffering from rheumatic diseases
Rheumatology (Oxford)
γδ T-cells: functional plasticity and heterogeneity
Nat Rev Immunol
Evidence-based guidelines for the use of immunologic tests: anticentromere, Scl-70, and nucleolar antibodies
Arthritis Rheum
Cited by (143)
Clinical correlates of a subset of anti-fibroblast antibodies in systemic sclerosis
2023, Clinical ImmunologyEsophageal epiphrenic diverticulum treated with laparoscopic surgery in a patient with systemic sclerosis: A rare case report
2023, International Journal of Surgery Case ReportsGastrointestinal Tract Considerations: Part II: How Should a Rheumatologist Best Manage Common Lower Gastrointestinal Tract Complaints in Systemic Sclerosis?
2023, Rheumatic Disease Clinics of North AmericaGastrointestinal Tract Considerations Part I: How Should a Rheumatologist Best Manage Common Upper Gastrointestinal Tract Complaints in Systemic Sclerosis?
2023, Rheumatic Disease Clinics of North AmericaNK cells - Dr. Jekyll and Mr. Hyde in autoimmune rheumatic diseases
2022, International ImmunopharmacologyThe Role of Epigenetics in Autoimmune Disorders
2022, Handbook of Epigenetics: The New Molecular and Medical Genetics, Third Edition