title: 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.
authors.affiliation: Clinical Immunology Unit, Department of Medicine, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Rua D. Manuel II, s/n, 4099-001, Porto, Portugal. isabel.almeida40@gmail.com.|Multidisciplinary Unit for Biomedical Investigation (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal. isabel.almeida40@gmail.com.
authors.forename: Isabel
authors.initials: I
authors.lastname: Almeida
authors.affiliation: Clinical Immunology Unit, Department of Medicine, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Rua D. Manuel II, s/n, 4099-001, Porto, Portugal. nevessp@gmail.com.
authors.forename: Sara Vieira
authors.initials: SV
authors.lastname: Silva
authors.affiliation: Laboratory of Cytometry, Department of Haematology, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Porto, Portugal.
authors.forename: Ana Raquel
authors.initials: AR
authors.lastname: Fonseca
authors.affiliation: Clinical Immunology Unit, Department of Medicine, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Rua D. Manuel II, s/n, 4099-001, Porto, Portugal. heitor.ivone@gmail.com.|Department of Vascular Surgery, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Porto, Portugal. heitor.ivone@gmail.com.
authors.forename: Ivone
authors.initials: I
authors.lastname: Silva
authors.affiliation: Clinical Immunology Unit, Department of Medicine, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Rua D. Manuel II, s/n, 4099-001, Porto, Portugal. cvcarlosvasconcelos@gmail.com.|Multidisciplinary Unit for Biomedical Investigation (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal. cvcarlosvasconcelos@gmail.com.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vasconcelos
authors.affiliation: Laboratory of Cytometry, Department of Haematology, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Porto, Portugal. mmc.lima@clix.pt.|Multidisciplinary Unit for Biomedical Investigation (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal. mmc.lima@clix.pt.
authors.forename: Margarida
authors.initials: M
authors.lastname: Lima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D058408:Th1-Th2 Balance; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: CD4; CD56; CD8; Cytokines; NK cells; Systemic sclerosis; T cells