Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 188, Issue 2, Pages 311-322Publisher
WILEY
DOI: 10.1111/cei.12939
Keywords
Behcet's disease; immunopathology; immunotherapies and innate immunity; NK cells
Categories
Funding
- Research Centre for Clinical and Diagnostic Oral Sciences
- Institute of Dentistry, Barts
- London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Wellcome Trust [096954/Z/11]
- National Institute for Health Research [CL-2014-19-005] Funding Source: researchfish
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Behcet's disease (BD) is an autoinflammatory, chronic relapsing/remitting disease of unknown aetiology with both innate and acquired immune cells implicated in disease pathogenesis. Peripheral blood natural killer (NK) cells and their CD56(Dim)/CD56(Bright) subsets were surface phenotyped using CD27 and CD16 surface markers in 60 BD patients compared to 60 healthy controls (HCs). Functional potential was assessed by production of interferon (IFN)-, granzyme B, perforin and the expression of degranulation marker CD107a. The effects of disease activity (BD(Active)versus BDQuiet) and BD medication on NK cells were also investigated. Peripheral blood NK cells (P<00001) and their constituent CD56(Dim) (P<00001) and CD56(Bright) (P=00015) subsets were depleted significantly in BD patients compared to HCs, and especially in those with active disease (BDActive) (P<00001). BD patients taking azathioprine also had significantly depleted NK cells compared to HCs (P<00001). A stepwise multivariate linear regression model confirmed BD activity and azathioprine therapy as significant independent predictor variables of peripheral blood NK percentage (P<0001). In general, CD56(Dim) cells produced more perforin (P<00001) and granzyme B (P<001) expressed higher CD16 levels (P<00001) compared to CD56(Bright) cells, confirming their increased cytotoxic potential with overall higher NK cell CD107a expression in BD compared to HCs (P<001). Interestingly, IFN- production and CD27 expression were not significantly different between CD56(Dim)/CD56(Bright) subsets. In conclusion, both BD activity and azathioprine therapy have significant independent depletive effects on the peripheral blood NK cell compartment.
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