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  • Manetti, Mirko  (3)
  • 2005-2009  (3)
  • 1
    Online Resource
    Online Resource
    Endothelial/lymphocyte activation leads to prominent CD4+ T cell infiltration in the gastric mucosa of patients with systemic sclerosis
    Wiley ; 2008
    In:  Arthritis & Rheumatism Vol. 58, No. 9 ( 2008-09), p. 2866-2873
    Details
    In: Arthritis & Rheumatism, Wiley, Vol. 58, No. 9 ( 2008-09), p. 2866-2873
    Abstract: Although gastrointestinal tract dysfunction is a common feature in patients with systemic sclerosis (SSc; scleroderma), few studies have addressed the pathogenetic mechanisms of gastrointestinal tract involvement in SSc. We previously showed that severe fibrosis and increased expression of profibrotic cytokines are important hallmarks in the gastric wall of patients with SSc. The aim of the present study was to investigate whether immune and/or microvascular abnormalities may account for tissue damage in gastric wall specimens obtained from patients with SSc. Methods Gastric biopsy samples from 27 patients with SSc and 15 healthy control subjects were analyzed by immunohistochemistry for CD45/leukocyte common antigen, CD3/T cells, CD4/T helper cells, CD8/cytotoxic T cells, CD20/B cells, CD14/monocytes, CD68/macrophages, cell adhesion molecules CD11a/lymphocyte function−associated antigen 1 (LFA‐1), CD49d/very late activation antigen 4 (VLA‐4), CD54/intercellular adhesion molecule 1 (ICAM‐1), CD106/vascular cell adhesion molecule 1 (VCAM‐1), CD31/platelet endothelial cell adhesion molecule 1, and vascular endothelial growth factor (VEGF). Results T cell infiltration was a prominent finding in gastric specimens from patients with SSc. The CD4+/CD8+ T cell ratio was significantly increased in SSc specimens compared with controls. T cells were found in both lymphocyte aggregates and diffuse infiltrates and strongly expressed the activation markers VLA‐4, LFA‐1, and ICAM‐1. Endothelial cells showed corresponding surface activation with strong expression of VCAM‐1 and ICAM‐1. Mature B cells were frequently observed arranged in aggregates and rarely were seen in a diffuse pattern. Most lymphocyte aggregates lacked monocyte/macrophages. No difference in microvascular density was observed between SSc specimens and controls. Both SSc and control specimens showed weak or no expression of VEGF. Conclusion Our findings provide the first evidence that endothelial/lymphocyte activation leading to prominent CD4+ T cell infiltration may play a key pathogenetic role within the gastric wall of patients with SSc and may represent an important therapeutic target.
    Type of Medium: Online Resource
    ISSN: 0004-3591 , 1529-0131
    URL: Issue
    URL: Article
    DOI: 10.1002/art.v58:9
    DOI: 10.1002/art.23806
    RVK:
    XA 10000
    RVK:
    XA 30325
    Language: English
    Publisher: Wiley
    Publication Date: 2008
    detail.hit.zdb_id: 2014367-9
    detail.hit.zdb_id: 127294-9
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  • 2
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    Severe fibrosis and increased expression of fibrogenic cytokines in the gastric wall of systemic sclerosis patients
    Wiley ; 2007
    In:  Arthritis & Rheumatism Vol. 56, No. 10 ( 2007-10), p. 3442-3447
    Details
    In: Arthritis & Rheumatism, Wiley, Vol. 56, No. 10 ( 2007-10), p. 3442-3447
    Abstract: Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and internal organs. Although the esophagus is the most frequently affected part of the gastrointestinal tract, all other segments can be involved. The present study was undertaken to evaluate the fibrotic process and the expression of fibrogenic cytokines in the gastric wall of SSc patients with gastroesophageal involvement. Methods Full‐thickness surgical and endoscopic gastric biopsy samples were obtained from 14 SSc patients and 10 controls. Tissue sections were either stained with Masson's trichrome or by immunohistochemistry and analyzed for the expression of types I, III, and IV collagen, α‐smooth muscle actin (α‐SMA), transforming growth factor β (TGFβ), connective tissue growth factor (CTGF), and endothelin 1 (ET‐1). Results In the gastric wall of SSc patients, Masson's trichrome staining and immunohistochemistry for types I and III collagen revealed a high amount of collagen in the lamina propria that increased toward the muscularis mucosae. In addition, muscle layers showed features of atrophy, with wide areas of focal fibrosis surrounding smooth muscle cells. Type IV collagen was present around glands and small vessels, suggesting a thickening of the basal lamina. The expression of the fibrogenic cytokines TGFβ and CTGF, ET‐1, and the myofibroblast marker α‐SMA was stronger in SSc patients than in controls. Conclusion A pronounced deposition of collagen, the presence of myofibroblasts, and increased expression of several profibrotic factors are important hallmarks in the stomach of patients with SSc. The fibrotic involvement of the gastric wall may account for muscle atrophy leading to stomach hypomotility in SSc.
    Type of Medium: Online Resource
    ISSN: 0004-3591 , 1529-0131
    URL: Issue
    URL: Article
    DOI: 10.1002/art.v56:10
    DOI: 10.1002/art.22940
    RVK:
    XA 10000
    RVK:
    XA 30325
    Language: English
    Publisher: Wiley
    Publication Date: 2007
    detail.hit.zdb_id: 2014367-9
    detail.hit.zdb_id: 127294-9
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Analysis of vascular gene expression in arthritic synovium by laser‐mediated microdissection
    Wiley ; 2007
    In:  Arthritis & Rheumatism Vol. 56, No. 4 ( 2007-04), p. 1094-1105
    Details
    In: Arthritis & Rheumatism, Wiley, Vol. 56, No. 4 ( 2007-04), p. 1094-1105
    Abstract: In rheumatoid arthritis (RA), formation of new blood vessels is necessary to meet the nutritional and oxygen requirements of actively proliferating synovial tissue. The aim of this study was to analyze the specific synovial vascular expression profiles of several angiogenesis‐related genes as well as CD82 in RA compared with osteoarthritis (OA), using laser‐mediated microdissection (LMM). Methods LMM and subsequent real‐time polymerase chain reaction were used in combination with immunohistochemical analysis for area‐specific analysis of messenger RNA (mRNA) and protein expression of vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR‐1), VEGFR‐2, hypoxia‐inducible factor 1α (HIF‐1α), HIF‐2α, platelet‐derived growth factor receptor α (PDGFRα), PDGFRβ, inhibitor of DNA binding/differentiation 2 (Id2), and CD82 in RA and OA synovial microvasculature and synovial lining. Results Expression of Id2 mRNA was significantly lower in RA synovial vessels compared with OA synovial vessels ( P = 0.0011), whereas expression of VEGFR‐1 was significantly higher in RA ( P = 0.0433). No differences were observed for the other parameters. At the protein level, no statistically significant differences were observed for any parameter, although Id2 levels were 2.5‐fold lower in RA ( P = 0.0952). However, the number of synovial blood vessels and the number of VEGFR‐2–expressing blood vessels were significantly higher in RA compared with OA. Conclusion Our results underscore the importance of area‐specific gene expression analysis in studying the pathogenesis of RA and support LMM as a robust tool for this purpose. Of note, our results indicate that previously described differences between RA and OA in the expression of angiogenic molecules are attributable to higher total numbers of synovial and vascular cells expressing these molecules in RA rather than higher expression levels in the individual cells.
    Type of Medium: Online Resource
    ISSN: 0004-3591 , 1529-0131
    URL: Issue
    URL: Article
    DOI: 10.1002/art.v56:4
    DOI: 10.1002/art.22450
    RVK:
    XA 10000
    RVK:
    XA 30325
    Language: English
    Publisher: Wiley
    Publication Date: 2007
    detail.hit.zdb_id: 2014367-9
    detail.hit.zdb_id: 127294-9
    Location Call Number Limitation Availability
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