Peripheral blood leukocyte immune responses in sarcoidosis

Fraser, Simon D.

September 2016

Thesis or dissertation

© 2016 Simon D Fraser. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown aetiology with heterogeneous clinical manifestations. The disease is characterised by elevated Th1-like pro-inflammatory immune responses in tissue, whereas peripheral blood has been described as either having enhanced, diminished or similar responses in patients compared with healthy controls. The aim of this study was to characterise the immune responses from peripheral leukocytes in patients with sarcoidosis, focussing on inflammatory and regulatory features present in the disease.

Immunophenotyping of peripheral blood mononuclear cells (PBMCs) by flow cytometry showed that 86% of patients with sarcoidosis displayed a T-cell lymphocytopenia, with over a 2 fold reduction in cell number compared to healthy controls, confirming the findings of other groups. The proportion of the more pro-inflammatory ‘Intermediate’ monocyte subset (CD14++ CD16+) was increased in patients with sarcoidosis, matched by a reduction in the ‘Classical’ monocyte subset (CD14++ CD16-).

High concentrations of phytohaemagglutinin (PHA) induced significantly increased IL-6 and TNF-α release from the blood of patients with sarcoidosis compared with controls in ex vivo whole blood assays. By contrast, IL-6 release in response to a high concentration of Staphylococcal enterotoxin A was significantly reduced in patients. There was no statistically significant difference in cytokine release from patients compared with controls when whole blood was treated with a range of other ligands and cytokines.
The regulatory CD200 receptor (CD200R) expression was reduced on monocytes from patients with sarcoidosis, whereas there was no significant difference in IL-10 receptor or SIRP-α expression between patients and controls. The CD200Rlow phenotype on monocytes was associated with elevated PHA induced IL-6 and TNF-α release from whole blood.

Patients with sarcoidosis are capable of robust peripheral blood leukocyte immune responses and display alterations in the regulatory CD200R/CD200L axis that may play a role in the immuopathogenesis of the disease.

Hull York Medical School, The University of Hull and University of York
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