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AB0170 Diminished peripheral t-cell activation along with marked th17 circulating profile in ssc
  1. E Krasimirova1,
  2. D Kalinova2,
  3. T Velikova1,
  4. E Ivanova-Todorova1,
  5. K Tumangelova-Yuzeir1,
  6. R Rashkov2,
  7. D Kyurkchiev1
  1. 1Laboratory of Clinical immunology
  2. 2Clinic of Rheumatology, University Hospital St. Ivan Rilski, Medical University of Sofia, Sofia, Bulgaria

Abstract

Background Systemic sclerosis (SSc) is a rare, debilitating connective tissue disease characterized by immunological alterations, vasculopathy and progressive skin and multiorgan fibrosis. The autoimmune dysregulation in SSc comprises lymphocyte activation that leads to autoantibody production, abnormal production of cytokines and chemokines, and impairment of the innate immunity. Recent research has shown that the T cell activation and especially T helper cells play an important role in the pathogenesis of SSc. Amongst them are the proinflammatory Th17 cells.

Objectives To investigate T-cell activation, the percentage of Th17 cells and the circulating cytokine profile in SSc.

Methods We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc (dcSSc, n=13) or limited cutaneous SSc (lcSSc, n=11). Peripheral venous blood samples were collected from all subjects. We examined the percentage of activated T cells (unstimulated and upon stimulation with PHA-M) and of Th17 cells by flow cytometry in both patients and controls. We used ELISA to quantitate the serum levels of human IL-6, TGF-β1, and IL-17A.

Results We identified a decreased percentage of activated T cells (CD3+CD69+) in PHA-stimulated samples from SSc patients in comparison with healthy controls, p<0.001. However, we did not establish a correlation between the down-regulated CD3+CD69+ cells and the SSc phenotype.

With regard to Th17 cells, our patients demonstrated increased percentage as opposed to controls, p=0.031. We detected up-regulated Th17 cells within the lcSSc subset against controls, p=0.025. However, no difference was found between dcSSc and lcSSc patients. Regarding the peripheral cytokine profile, we detected raised levels of IL-6, p<0.001, TGF-β1, p=0.02, and IL-17A, p<0.001 in patients when compared to controls. Furthermore, we found increased circulating TGF-β, IL-6 and IL-17A in the lcSSc subset versus healthy individuals, as it follows TGF-β1, p=0.031, IL-6, p<0.001, and IL-17A, p<0.001. Furthermore, circulating IL-17A was higher in lcSSc as opposed to dcSSc subset, p=0.008. Within the dcSSc phenotype, we detected raised levels of IL-17A and IL-6 versus controls: IL-17A, p<0.001, IL-6, p<0.001.

Conclusions Our results demonstrate down-regulated T-cell activation upon PHA-stimulation along with pronounced peripheral Th17 profile, and related cytokines in SSc patients, suggesting their implication in the pathogenesis of SSc.

References

  1. Brembilla NC, Chizzolini C. T cell abnormalities in systemic sclerosis with a focus on Th17 cells. Eur Cytokine Netw 2012; 23 (4): 128–139.

  2. Raja J, Denton CP. Cytokines in immunopathology of systemic sclerosis. Semin Immunopathol 2015; 37 (5): 543–557.

References

Disclosure of Interest None declared

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