Leukocyte Toll-like Receptor expression in Pathergy Positive and Negative Behçet's Disease Patients

Overview

Journal Rheumatology (Oxford)

Publisher Oxford University Press

Specialty Rheumatology

Date 2020 Aug 7

PMID 32756992

Citations 10

Authors

Tim B van der Houwen

Willem A Dik

Marco Goeijenbier

Manizhah Hayat

Nicole M A Nagtzaam

Martin van Hagen

Jan A M van Laar

Affiliations

Soon will be listed here.

Abstract

Objectives: To investigate whether the auto-inflammatory nature and the pathergic reaction in Behçet's disease (BD) are driven by a disturbed toll-like receptor (TLR) response.

Methods: We compared both TLR expression by flow-cytometry and TLR response by stimulation assay in 18 BD patients (both pathergy positive and pathergy negative) with 15 healthy controls.

Results: Expression of TLR1 and 2 was significantly elevated in B-lymphocytes of BD patients compared with healthy controls. TLR1, 2 and 4 were significantly more highly expressed in both CD4+ and CD8+ T-lymphocytes of BD patients. Granulocytes of BD patients displayed significantly higher expression of TLR1, 2, 4 and 6. TLR2, 4 and 5 expression was significantly increased on classical monocytes of BD patients. Intermediate monocytes of BD patients showed an increase in expression of TLR2. Furthermore, TLR2 and 5 were significantly more highly expressed in non-classical monocytes of BD patients. In pathergy positive patients, TLR5 was even more highly expressed compared with pathergy negative patients on B- and T-lymphocytes and granulocytes. Furthermore, TLR2 and 5 showed an elevated TNF-α response to stimulation with their cognate ligands.

Conclusion: Immune cells of BD patients overexpress TLR1, 2, 4, 5 and 6. Furthermore, after stimulation of TLR2 and 5, BD patients demonstrate a more potent TNF-α response. Although this is a small cohort, in the pathergy positive patients, TLR5 expression is even further augmented, suggesting that a microbial (flagellin) or damage (HMGB1) associated signal may trigger the exaggerated immune response that is characteristic for the pathergy phenomenon in BD. In conclusion, these results point to an exaggerated TLR response in the auto-inflammatory nature of BD.

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