T and NK Cell Phenotypic Abnormalities in Systemic Sclerosis: a Cohort Study and a Comprehensive Literature Review

Abstract

Scleroderma (SSc) is a rare and heterogeneous immune-mediated disease involving the connective tissue and microvasculature whose pathogenesis remains unclear. Data concerning T and natural killer (NK) cell abnormalities and cytokine levels in the peripheral blood (PB) from patients with SSc are scarce, and the results are contradictory. The present study aimed to analyze the changes of T lymphocytes, NK cells, and T helper (Th)-related cytokines in the PB of patients with SSc in comparison to healthy individuals and its relation to disease subtype and stage, organ involvement, and nailfold capillaroscopic changes. A non-random convenience sample of 57 scleroderma patients was utilized. Fifty-five out of the 57 patients studied were women (97 %); 10 patients presented pre-scleroderma (pre-SSc) and 47 SSc: 34 limited cutaneous SSc (lcSSc) and 13 diffuse cutaneous SSc (dcSSc). Patients with SSc were classified in early (n = 7), intermediate (n = 10), and late (n = 30) disease. Blood samples were analyzed by flow cytometry for total T cells, CD4+ and CD8+ T cell subsets, total NK cells, and CD56+low and CD56+high NK cell subsets. T cells were further analyzed for the expression of the CD56 adhesion molecule and activation-related markers (HLA-DR, CD45RO). In addition, the serum levels of Th1-, Th2-, and Th17-related cytokines were measured by flow cytometry. Twenty-five healthy individuals recruited from the blood bank were used as controls. Patients had lower numbers of total lymphocytes and T cells comparing to healthy controls. Both CD4+ and CD8+ T cells were decreased, but differences were statistically significant only for CD8+ and CD8+ CD45RO+ T cells. These alterations were seen in patients with SSc but not in patients with pre-SSc, and, in general, they were more pronounced in patients with dcSSc than in patients with lcSSc, in patients with vascular involvement than in those without, as well as in patients having active and late nailfold capillaroscopic patterns. CD56+ T cells were also decreased in SSc patients, especially in those with active/late capillaroscopic patterns or with severe lung disease. Diminished numbers of circulating NK cells were also observed in patients with lcSSc and in those with early disease. No statistically significant changes were found in serum cytokine levels, as compared with controls. Patients with SSc had major alterations in circulating CD8+ and CD56+ T cells, as well as in NK cells, suggesting that these cells may play a relevant role in SSc pathogenesis, probably operating at different phases and/or at different organs. In addition, the serum levels of Th1, Th2, and Th17 cytokines did not provide useful information for evaluating T cell polarization in SSc.

Cytometry by time of flight identifies distinct signatures in patients with systemic sclerosis, systemic lupus erythematosus and Sjögrens syndrome

“…Here we applied CYTOF to directly compare different SADs in an attempt to dissect both distinct and overlapping patterns of circulating immune cells thereby aiming at molecular classification of SADs rather than on their diagnostic vignettes. Our results confirmed recent observations in patients with pSS by Mingeneau et al, as well as a previously observed decrease of CD56 + NK-cells in SSc patients [8][9][10]. In addition, we identified both overlapping and distinct immune cell phenotypic alterations among patients with SSc, SLE, and pSS.…”

Human CD56bright NK Cells: An Update

“…In Sjögren's syndrome, this subset is also increased, regardless of disease activity (44). In contrast, circulating CD56 bright NK cells are decreased in juvenile dermatomyositis (45) and in systemic sclerosis (46).…”

CD56 in the Immune System: More Than a Marker for Cytotoxicity?

“…Regarding autoimmune diseases, patients suffering from systemic sclerosis, mainly those with active/late capillaroscopic patterns or with severe lung impairment, have decreased numbers of circulating CD56 + CTLs as compared to healthy individuals (60). Even though different mechanisms may be involved, this decline in CD56 + T cells in the peripheral blood results at least in part from the recruitment and/or trafficking of these cells to the affected tissues, where they cause endothelial cell injury and apoptosis (32).…”