Circulating NK cells and their subsets in Behçet's disease.
Behçet'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 CD56Dim/CD56Brightsubsets 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)-γ, granzyme B, perforin and the expression of degranulation marker CD107a. The effects of disease activity (BDActiveversus BDQuiet) and BD medication on NK cells were also investigated. Peripheral blood NK cells (P < 0·0001) and their constituent CD56Dim(P < 0·0001) and CD56Bright(P = 0·0015) subsets were depleted significantly in BD patients compared to HCs, and especially in those with active disease (BDActive) (P < 0·0001). BD patients taking azathioprine also had significantly depleted NK cells compared to HCs (P < 0·0001). A stepwise multivariate linear regression model confirmed BD activity and azathioprine therapy as significant independent predictor variables of peripheral blood NK percentage (P < 0·001). In general, CD56Dimcells produced more perforin (P < 0·0001) and granzyme B (P < 0·01) expressed higher CD16 levels (P < 0·0001) compared to CD56Brightcells, confirming their increased cytotoxic potential with overall higher NK cell CD107a expression in BD compared to HCs (P < 0·01). Interestingly, IFN-γ production and CD27 expression were not significantly different between CD56Dim/CD56Brightsubsets. In conclusion, both BD activity and azathioprine therapy have significant independent depletive effects on the peripheral blood NK cell compartment.
Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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Hasan
Centre for Adult Oral Health, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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Ryan
Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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0000-0001-9843-4218
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Bergmeier
Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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Fortune
D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D001528:Behcet Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D001775:Blood Circulation / Q000276:immunology*; D019002:CD56 Antigen / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D053804:Granzymes / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000737:chemistry / Q000145:classification / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000096:biosynthesis; D017452:Receptors, IgG / Q000235:genetics; D055815:Young Adult
D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D052118:Lysosomal-Associated Membrane Protein 1; D017452:Receptors, IgG; D054353:Perforin; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D001379:Azathioprine
Behçet's disease; NK cells; immunopathology; immunotherapies and innate immunity