In situ Expression of Cytokines and Cellular Adhesion Molecules in the Skin of Patients with Systemic Sclerosis

Koch, Alisa E.; Kronfeld-Harrington, L B; Szekanecz, Z.; Cho, M M; Haines, G. Kenneth; Harlow, Lisa A.; Strieter, R. M.; Kunkel, S L; Massa, Mary C.; Barr, Walter G.

doi:10.1159/000163802

Cited by 153 publications

(108 citation statements)

References 24 publications

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“…Further studies focused on rightsided heart catheterization, and hemodynamic parameters are needed. Since VCAM-1 and E-selectin expressions are also elevated in EC activation (28), and only a weak correlation of sVCAM-1 and sCD90 was observed, another potential source of sCD90 in SSc might be fibroblasts. In fibroblast foci of patients with idiopathic pulmonary fibro- sis, only CD90 fibroblasts/myofibroblasts could be detected, whereas in healthy controls, CD90ϩ fibroblasts predominate (14,36).…”

Section: Discussionmentioning

confidence: 99%

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Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis

Kollert¹,

Christoph²,

Probst³

et al. 2013

Arthritis Care & Research

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Objective. Vascular injury and endothelial cell (EC) activation are pathogenic hallmarks of systemic sclerosis (SSc; scleroderma). Human CD90 is highly expressed on activated ECs and can be shed from the cell surface. This study was conducted to examine whether soluble CD90 (sCD90) is elevated in the sera of patients with SSc and linked to pulmonary involvement and in particular, pulmonary arterial hypertension (PAH). Methods. sCD90 serum concentrations were assessed in 76 patients with SSc and related to clinical data, lung function, 6-minute walk distance, echocardiography, bronchoalveolar lavage fluid, and laboratory parameters. Thirty-one healthy volunteers and 29 patients with idiopathic retroperitoneal fibrosis (IRF) served as controls. Results. sCD90 serum concentrations were elevated in patients with SSc compared to healthy volunteers (P ‫؍‬ 0.001) and patients with IRF (P ‫؍‬ 0.01). SSc patients with pulmonary fibrosis (P ‫؍‬ 0.006) and patients with PAH (P < 0.001) had increased sCD90 serum concentrations compared to patients without the respective pulmonary manifestation of SSc. sCD90 levels correlated with diffusing capacity for carbon monoxide (n ‫؍‬ 65; r ‫؍‬ ؊0.348, P ‫؍‬ 0.005) and systolic pulmonary artery pressure (n ‫؍‬ 53; r ‫؍‬ 0.469, P < 0.001). Receiver operating characteristic curve testing determined an optimal cutoff value of >626 ng/ml with a sensitivity of 68% and a specificity of 83% for PAH (area under the curve 0.773, 95% confidence interval 0.648 -0.898; P < 0.001). Conclusion. sCD90 concentrations were increased in the sera of SSc patients, particularly in patients with vascular involvement of the lungs. These data suggest that sCD90 should be further evaluated as a marker for diagnosis of PAH in SSc.

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Section: Discussionmentioning

confidence: 99%

“…ECs express several adhesion molecules (28). CD90 is a member of the immunoglobulin superfamily (7) and as such, like other adhesion molecules, is involved in cellcell adhesion and the recruitment of leukocytes via Mac-1 (CD11b/CD18) (29).…”

Section: Discussionmentioning

confidence: 99%

Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis

Kollert¹,

Christoph²,

Probst³

et al. 2013

Arthritis Care & Research

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“…Increased levels of CXCL8 protein have been observed in SSc skin biopsy specimens (28) and in bronchoalveolar lavage fluid from patients with SSc (29). Scleroderma fibroblasts cultured in vitro were found to produce more CXCL8 than that in normal fibroblasts (30).…”

Section: Discussionmentioning

confidence: 99%

Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis

Lee¹,

Zhao²,

Kim³

et al. 2007

Arthritis & Rheumatism

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Objective. To examine genetic polymorphisms in the chemokine pathway, and to assess their interactions in relation to susceptibility to systemic sclerosis (SSc).Methods. To identify the risk of SSc conferred by genetic polymorphisms in the chemokine pathway, 10 single-nucleotide polymorphisms (SNPs) from 8 candidate genes were studied in 99 patients with SSc and 198 age-and sex-matched controls in a Korean population. SNPs were genotyped by polymerase chain reactionrestriction fragment length polymorphism or sequencespecific primer methods. Genetic associations between each SNP and SSc risk, calculated as odds ratios with 95% confidence intervals, were estimated using chisquare tests. Haplotypes for the 2 polymorphisms in the gene CCL5 (RANTES) were constructed, and their associations with SSc were tested. Gene-gene interactions were investigated using a recently described novel method, and the results were confirmed by conditional logistic regression. Adjustment for multiple testing was based on Bonferroni correction.Results. There was significant evidence of genegene interaction between polymorphisms in the genes CXCL8 (interleukin-8) and CCL5, and both of these were associated with an increased risk of SSc. This SNP-SNP interaction was confirmed by 2 independent statistical methods. The associations remained significant after Bonferroni adjustment for multiple testing. No significant association between each individual SNP or haplotype and the risk of SSc was found.Conclusion. Crosstalk between the 2 chemokines CXCL8 and CCL5 may contribute to the susceptibility to SSc.

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“…Stem cell yield may be dependent on a disease-specific cytokine and chemokine milieu, as well as adhesion molecules and the bone marrow microenvironment. [45][46][47][48][49][50][51][52] When corrected for mobilizing regimen, weight and apheresis volume, patients with SSc had the best cell recovery. Patients with RA, MS, and ITP had similar but lower progenitor cell yields.…”

Section: Bone Marrow Transplantationmentioning

confidence: 99%

Collection of hematopoietic stem cells from patients with autoimmune diseases

Burt

Fassas

Snowden

et al. 2001

Bone Marrow Transplant

135

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Summary:We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harvests and 174 peripheral blood stem cell mobilizations were performed on 187 patients. Disease indications were multiple sclerosis (76 patients), rheumatoid arthritis (37 patients), scleroderma (26 patients), systemic lupus erythematosus (19 patients), juvenile chronic arthritis (13 patients), idiopathic autoimmune thrombocytopenia (8 patients), Behcet's disease (3 patients), undifferentiated vasculitis (3 patients), polychondritis (1 patient) and polymyositis (1 patient). Bone marrow harvests were used in the Peoples Republic of China and preferred worldwide for children. PBSC mobilization was the preferred technique for adult stem cell collection in America, Australia, and Europe. Methods of PBSC mobilization included G-CSF (5, 10, or 16 g/kg/day) or cyclophosphamide (2 or 4 g/m 2 ) with either G-CSF (5 or 10 g/kg/day) or GM-CSF (5 g/kg/day). Bone marrow harvests were without complications and did not affect disease activity. A combination of cyclophosphamide and G-CSF was more likely to ameliorate disease activity than G-CSF alone (P Ͻ 0.001). G-CSF alone was more likely to cause disease exacerbation than the combination of cyclophosphamide and G-CSF (P = 0.003). Three patients died as a result of cyclophosphamide-based stem cell collection (2.6% of patients mobilized with cyclophosphamide). When corrected for patient weight and apheresis volume, progenitor cell

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In situ Expression of Cytokines and Cellular Adhesion Molecules in the Skin of Patients with Systemic Sclerosis

Cited by 153 publications

References 24 publications

Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis

Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis

Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis

Collection of hematopoietic stem cells from patients with autoimmune diseases

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