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A3.25 systemic sclerosis patients exhibit an increased frequency of T cells and NK cells with effector/cytotoxic phenotype
  1. Tiago Carvalheiro1,
  2. Ângela Andrade2,
  3. Magda Lemos2,
  4. Mariana Galante Santiago3,
  5. Cláudia Silva4,
  6. Maria João Salvador3,
  7. José António Pereira da Silva3,
  8. Artur Paiva1,2
  1. 1Blood and Transplantation Center of Coimbra | Portuguese Institute of Blood and Transplantation, Coimbra, Portugal
  2. 2College of Health Technology of Coimbra, Coimbra, Portugal
  3. 3Rheumatology Department – University Hospital Center of Coimbra, Coimbra, Portugal
  4. 4University of Aveiro, Aveiro, Portugal

Abstract

Background Systemic sclerosis (SSc) is an inflammatory and fibrotic disease characterised by inflammation, immune dysregulation and excessive extracellular matrix deposition. T cell and NK cell disturbance have already been described in SSc and implicated in its establishment.

Aims Determine the frequency of different subpopulations of T cells (CD4+, CD8+ and CD4+ /CD8+) among the functional compartments and the percentage of T cell subsets and NK cells (CD56bright and CD56dim subpopulations) expressing cytolytic markers.

Materials and Methods The study enrolled 43 SSc patients, 30 with limited cutaneous subtype (lSSc) and 13 with diffuse cutaneous subtype (dSSc) according to LeRoy et al. classification and 20 healthy individuals as control group. A further subdivision was made based upon clinical parameters of disease duration and clinical manifestations.

Immunophenotyping characterisation of peripheral blood T cells was performed by flow cytometry. T cells functional compartments (naïve, central memory, effector memory and terminal effector) were defined based on CD45Ra and CD27 phenotype. Cytotoxic activity was assessed by the intracellular expression of granzyme B and perforin.

Results We observed a lower frequency of T cells in SSc, particularly in dSSc and in patients with pulmonary fibrosis and digital ulcers. Moreover, SSc patients presented a decreased frequency and absolute numbers of CD8+ T cells (mainly in dSSc patients, and SSc patients with pulmonary fibrosis and digital ulcers). We also observed a lower absolute value of double positive CD4+/CD8+ cells in SSc patients. Regarding NK cells, SSc patients with pulmonary fibrosis exhibit a lower absolute value of both CD56bright and CD56dim subsets.

Among functional compartments, we found a higher frequency of CD8+ and CD4+ T cells with terminal effector and memory effector phenotype, closely related to a decreased frequency of cells with central memory and naïve phenotype. This reached statistical significance for CD8+ T cells. In line with these observations, we demonstrated an increased frequency of T CD4+ and CD8+ cells expressing granzyme B and perforin, particularly in patients with the disease for longer than one year. An increased frequency of CD56bright NK cells expressing perforin or granzyme B was also observed in SSc patients.

Conclusions Our results indicate an increased frequency of CD4+ and CD8+ T cells and CD56bright NK cells with an effector/cytotoxic phenotype in the peripheral blood from SSc patients. These changes seem to be related with the presence of pulmonary fibrosis or digital ulcers.

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