Ultrastructure of cutaneous cellular infiltrates in scleroderma

Fleischmajer, R.

doi:10.1001/archderm.113.12.1661

Cited by 28 publications

(17 citation statements)

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“…They found no association with disease dura- in blood (n = 14) tion but made no attempt to correlate cellular infiltrates with disease severity or activity. In other studies, these infiltrates were found to be either predominantly T lymphocytes (3), or composed of T lymphocytes and monocytes/macrophages (19). Several in vitro studies have shown that soluble products of mononuclear cells (cytokines) can stimulate fibroblasts to synthesize increased amounts of collagen and other connective tissue substances (5,6).…”

Section: Discussionmentioning

confidence: 97%

Lymphocytes in the skin of patients with progressive systemic sclerosis

Roumm

Whiteside

Medsger

et al. 1984

Arthritis & Rheumatism

352

201

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Mononuclear cells (MNC) present in the dermis of the forearm and in the blood of patients with progressive systemic sclerosis (PSS) were quantified and analyzed for subsets using monoclonal antibodies. The findings were correlated with cutaneous and systemic features of the disease. Total T lymphocytes and their subsets, B cells, and macrophages were enumerated in the skin samples of 21 patients with PSS. The dermal MNC infiltrates consisted mostly of activated T lymphocytes with a mean T helper/T suppressor (T4/T8) ratio of 2.4 2 1.3 SD. Few B1-positive or TCpositive cells (macrophages) were observed. There was no correlation between the skin or blood T4/T8 ratios and the degree of skin thickening. On histologic examination, 58 of 115 (50%) untreated patients with PSS had prominent dermal MNC infiltration. Significant correlations between the degree of MNC infiltration and both the degree (P < 0.05) and progression (P < 0.05) of skin thickening were observed. No correlations with other systemic disease features of PSS were noted. These

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Section: Discussionmentioning

confidence: 97%

Lymphocytes in the skin of patients with progressive systemic sclerosis

Roumm

Whiteside

Medsger

et al. 1984

Arthritis & Rheumatism

352

201

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“…Past studies have suggested that SSc skin pathology evolves from inflammatory to fibrotic changes over time (Fleischmajer et al ., 1978; Fleischmajer et al ., 1977; Kraling et al ., 1995; Roumm et al ., 1984). Our molecular analyses suggest that inflammatory changes in the skin are not part of an evolving process leading to fibrosis, but rather represent a subset of patients, with other patients having significantly less skin inflammation as part of the pathologic process.…”

Section: Discussionmentioning

confidence: 99%

Intrinsic Gene Expression Subsets of Diffuse Cutaneous Systemic Sclerosis Are Stable in Serial Skin Biopsies

Pendergrass

Lemaire

Francis

et al. 2012

Journal of Investigative Dermatology

148

178

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Skin biopsy gene expression was analyzed by DNA microarray from 13 dSSc patients enrolled in an open label study of rituximab, 9 dSSc patients not treated with rituximab, and 9 healthy controls. These data recapitulate the patient ‘intrinsic’ gene expression subsets described previously including proliferation, inflammatory, and normal-like groups. Serial skin biopsies showed consistent and non-progressing gene expression over time, and importantly, the patients in the inflammatory subset do not move to the fibroproliferative subset, and vice versa. We were unable to detect significant differences in gene expression before and after rituximab treatment, consistent with an apparent lack of clinical response. Serial biopsies from each patient stayed within the same gene expression subset regardless of treatment regimen or the time point at which they were taken. Collectively, these data emphasize the heterogeneous nature of SSc and demonstrate that the intrinsic subsets are an inherent, reproducible and stable feature of the disease that is independent of disease duration. Moreover, these data have fundamental importance for the future development of personalized therapy for SSc; drugs targeting inflammation are likely to benefit those patients with an inflammatory signature, whereas drugs targeting fibrosis are likely to benefit those with a fibroproliferative signature.

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“…However, the mechanism by which fibroblast collagen synthesis becomes augmented is unknown. Histologic studies of early skin lesions in scleroderma patients have revealed increased numbers of fibroblasts (25). Fibroblast cultures established from explants of dermis from scleroderma patients have shown increased collagen accumulation (26).…”

Section: Discussionmentioning

confidence: 99%

Endothelin, an endothelial‐dependent vasoconstrictor in scleroderma. Enhanced production and profibrotic action

Kahaleh¹

1991

Arthritis & Rheumatism

225

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The vascular endothelium is an important functional unit in the regulation of the vascular and perivascular environment. Various chemical and physical stimuli mediate an endothelial-dependent vasoconstriction through the release of endothelial soluble factors, such as the recently recognized endothelium-derived vasoconstrictor peptide called endothelin. The presence of circulating endothelin and the effect of cold exposure on plasma endothelin levels were investigated in patients with scleroderma and in healthy control subjects. Radioimmunoassay demonstrated a mean f SD plasma level of 10.7 f 7.3 pg/ml in the patients (n = 19) and 3.7 f 2 in the control subjects (n = 16) (P < 0.005). These levels were also assessed in 5 control subjects and 5 scleroderma patients before and after 30 minutes of total body cooling (to 15OC). The endothelin level did not change significantly in either group; however, 2 scleroderma patients showed a significant increase after cooling. The effects of endothelin on fibroblast proliferation and collagen synthesis were evaluated in order to assess the impact of released endothelin on the interstitium. A significant mitogenic effect and a collagen synthesisenhancing effect, which were dose-dependent, were seen. The strong, characteristically prolonged, vasoconstrictor activity coupled with the profibrotic effect demonstrated here make it likely that disturbances in the From the Medical College of Ohio, Toledo.

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Ultrastructure of cutaneous cellular infiltrates in scleroderma

Cited by 28 publications

References 0 publications

Lymphocytes in the skin of patients with progressive systemic sclerosis

Lymphocytes in the skin of patients with progressive systemic sclerosis

Intrinsic Gene Expression Subsets of Diffuse Cutaneous Systemic Sclerosis Are Stable in Serial Skin Biopsies

Endothelin, an endothelial‐dependent vasoconstrictor in scleroderma. Enhanced production and profibrotic action

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