Background/Purpose: Diffuse cutaneous systemic sclerosis (dcSSc) is associated with significant morbidity and mortality. Measurement of skin thickness (modified Rodnan skin score (mRss)) is a surrogate of dcSSc severity as an increase in this score is associated with involvement of internal organs and increased mortality. Recent studies have found that high levels of the profibrotic type-2 cytokine IL-13 are produced by peripheral blood effector CD8+ T cells from SSc patients and that IL-13-producing circulating CD8+ T cells express skin-homing receptors and induce a profibrotic phenotype in normal dermal fibroblasts. Although one study describes a reduction of the circulating CD8+ T cell subset in dcSSc, the clinical implications of this finding are unknown.

Methods: The frequencies of circulating CD4, CD8, CD20 and CD14 cells were determined by multi-parameter fluorescence-activated cell sorting (FACS) in peripheral blood mononuclear cells isolated from newly diagnosed, untreated dcSSc patients. Samples from patients with early onset, untreated seropositive rheumatoid arthritis were tested as controls. Clinical parameters recorded at the time of sample collection included: mRss, global assessment of activity, global assessment of severity, forced vital capacity and DLCO.

Results: Percentages and absolute counts of cell subsets isolated from dcSSc patients (n=10) with a mean age of 58±8.24 years and a mean disease duration of 2.7±1.8 years were compared with age matched early onset RA patients (n=10). The frequencies of the studied cell subpopulations was similar between RA and dcSSc except for the absolute number and percentage of the CD8+ fraction, which was lower among dcSSc (p=.007 and .03, respectively). Lower frequencies of CD8+ T cells were associated with higher mRss and higher global assessments of activity (p=.0037 and .0052, respectively). For an increase of 1 unit in the mRSS score (range 0-51) there was a decrease of 0.79 in absolute CD8+ T cells and for an increase of 1 unit in the global assessment of activity (range 0-10), there was a decrease of 0.75 in absolute CD8+ T cells.

Conclusion: Our findings suggest that early dcSSc have lower frequencies of peripheral blood circulating CD8+ T cells and that those are inversely associated with skin scores and disease activity. These findings are particularly relevant in light of recent evidence suggesting that skin homing – relocation IL-13-producing CD8+ T cells are directly involved in modulating dermal fibrosis in SSc, and emphasizes the need to prospectively assess the utility of reduced CD8+ T cell frequencies as a biomarker of dcSSc severity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduced-frequencies-of-circulating-cd8-t-cells-in-early-diffuse-cutaneous-systemic-sclerosis-is-associated-with-worse-skin-scores/