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A3.23 Alterations in the distribution and pro-inflammatory activity of peripheral blood monocytes and dendritic cells subpopulations in systemic sclerosis
  1. Tiago Carvalheiro1,
  2. Sara Horta2,
  3. Mariana Santiago3,
  4. Maria João Salvador3,
  5. José António Pereira da Silva3,
  6. Artur Paiva1
  1. 1Blood and Transplantation Center of Coimbra | Portuguese Institute of Blood and Transplantation, Coimbra, Portugal
  2. 2University of Aveiro, Aveiro, Portugal
  3. 3Rheumatology Department – University Hospital Center of Coimbra, Portugal

Abstract

Background Systemic sclerosis (SSc) is a connective tissue disease characterised by immune and fibrotic abnormalities. Important observations suggest monocytes and dendritic cells (DCs) involvement in SSc, including abnormalities in differentiation, recruitment, trafficking, activation and an enhanced pro-fibrotic phenotype that could be important factors in the disease pathogenesis.

Objectives Evaluate the frequency of monocytes subpopulations (CD16- and CD16+ monocytes) and DCs subsets (myeloid – mDC, CD16+CD14-/low DCs and plasmacytoid DCs – pDCs) and their functional ability to produce chemokines (CXCL10, CCL4 and IL-8) in SSc patients.

Materials and Methods The study enrolled 43 SSc patients, 30 with limited cutaneous subtype (lSSc) and 13 with diffuse cutaneous subtype (dSSc). A further subdivision was made based upon clinical parameters of disease duration and organ involvement. The healthy control group (HC) included 20 age and gender matched individuals. Immunophenotyping of peripheral blood DC and monocytes subpopulations was assessed by flow cytometry and their functional characterisation was performed after LPS plus IFN-g stimulation.

Results We observed an increased frequency and absolute number of CD16+ monocytes in SSc patients, particularly in the lSSc group. These changes were more pronounced in patients with longer disease duration (>10 yrs). Concerning the DCs subsets, no differences were observed between the SSc subtypes and HG. Patients without pulmonary fibrosis demonstrated a higher frequency and absolute number of CD16+CD14-/low DCs than HG, while the differences were not statistically significant between patients with pulmonary fibrosis and HC. Patients with SSc for more than 10 years, demonstrated an increased frequency and absolute value of CD16+CD14-/low DCs in comparison to HG.

Without in vitro stimulation, we observed an increased frequency of CD16+CD14-/low DCs and mDCs expressing CCL4 and CXCL10, particularly in dSSc subtype. After in vitro stimulus, a higher frequency of CD16+CD14-/low DCs expressing IL-8 in dSSc subtype was observed. Moreover, the frequency of monocytes, CD16+CD14-/low DCs and mDCs expressing IL-8 and the frequency of CD16+CD14-/low DCs and mDCS expressing CCL4 was higher in patients with pulmonary fibrosis than in HC.

Conclusions Important alterations were observed in the frequency/absolute number of circulating monocytes and DCs subsets and their functional ability to produce chemokines in SSc patients, which seem to be related to disease duration and to pulmonary fibrosis.

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