Lack of increased expression of cell surface markers for circulating fibrocyte progenitors in limited scleroderma

Abstract

The aetiology and pathogenesis of scleroderma is incompletely understood. Recently, a cell called the fibrocyte has been shown to be derived from circulating monocytes with the ability to produce collagen. The aim of this study was to evaluate differences in the cell surface characteristics of circulating fibrocyte progenitors (monocytes) in patients with limited scleroderma compared to controls. A case-control study was performed in eight patients with limited scleroderma, which were matched with eight controls. Three-colour flow cytometry was used to assess the relative expression of cell surface markers. Statistical analysis then compared the relative expression between the two groups. In this preliminary study, there were no significant differences in the expression of circulating monocyte surface molecules involved with cell transformation, function, or migration presumed to give rise to fibrocytes, in a population of patients with limited scleroderma. Various explanations for the results are discussed.

Fibrocytes: Bringing new insights into mechanisms of inflammation and fibrosis

“…In a separate study using the same model, investigators stained skin samples from normal mice, bleomycin-treated wild type A 2A receptor knock-out mice, and A 2A antagonist-treated mice for procollagen α2 Type I and CD34 (fibrocytes) (Katebi et al, 2008): the investigators found more fibrocytes in the dermis of the bleomycin-treated mice compared to the normal mice, and the increase in fibrocyte number was abrogated by blockade of the adenosine A 2A receptor, suggesting that recruitment of fibrocytes into tissue plays an important role in scleroderma. While a small case–control study of 8 patients with limited scleroderma, showed no difference between cases and controls in the expression of circulating monocyte surface molecules associated with fibrocytes (Russo et al, 2007), the study had major limitations including a small sample size and the enrollment of patients with limited scleroderma only.…”

Circulating progenitor cells and scleroderma

“…One report suggested that scleroderma patients may have increased circulating CD14 + cells that can differentiate into CD34 − fibroblast-like cells [31]. In a recent study of eight scleroderma patients and eight controls, no difference was seen in the percent of circulating CD14 + /CD45 + monocytes expressing several cell surface markers, but these authors did not examine the expression of collagen on these cells or their differentiation into fibrocytes [32]. In a very exciting new finding in the fibrosis field, patients with pulmonary fibrosis were found to have an increased number of circulating CD45 + /collagen I + cells [33••].…”

Monocyte Gene Expression Signatures in Rheumatic Diseases: Biomarkers for Disease Activity and Tools for Diagnosis and Classification

“…Interestingly monocytes of early SSc patients (and not of chronic SSc, RA and SLE patients) show an up regulation of the tumor necrosis factor converting enzyme (TACE) [39]. However, further phenotyping of CD14+ monocytes by flowcytometry in SSc patients with limited disease did not reveal differences in a number of the cell surface markers associated with activation, migration and transformation [40].…”

“…Interestingly monocytes of early SSc patients (and not of chronic SSc, RA and SLE patients) show an up regulation of the tumor necrosis factor converting enzyme (TACE) [39]. However, further phenotyping of CD14+ monocytes by flowcytometry in SSc patients with limited disease did not reveal differences in a number of the cell surface markers associated with activation, migration and transformation [40].In summary, the phenotypic and functional analysis of monocytes in rheumatic diseases is elaborate and has revealed a heterogeneous picture with inconsistent and sometimes contradictory results. Functional assays as described above are apparently not precise and robust enough to determine the complex abnormalities of monocytes in rheumatic disease patients.…”