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Circulating NK cells and their subsets in Beh ç et's disease

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ABSTRACT

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/CD56Bright 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)‐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, CD56Dim cells produced more perforin (P < 0·0001) and granzyme B (P < 0·01) expressed higher CD16 levels (P < 0·0001) compared to CD56Bright cells, 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/CD56Bright subsets. In conclusion, both BD activity and azathioprine therapy have significant independent depletive effects on the peripheral blood NK cell compartment.

No MeSH data available.


Related in: MedlinePlus

Natural killer (NK) cell peripheral blood percentage is reduced significantly in patients under azathioprine therapy. (a) NK cells expressed as a percentage of total gated lymphocytes was compared in patients on different forms of Behçet's disease (BD) medication; colchicine (BDCol), prednisolone (BDPred), mycophenolate mofetil (BDMMF) and azathioprine (BDAza) and compared to healthy controls (HC) as well as patients not currently taking BD‐associated medication (BDNo therapy). (b) NK cell percentage expressed as a percentage of total lymphocytes in BD patients subgrouped according to disease activity (BDQuiet/Active) and whether currently taking azathioprine or not (BDAza or BDNon‐Aza). *P < 0·05; **P < 0·001; ***P < 0·001. Aza = azathioprine; Col = colchicine; MMF = mycophenolate mofetil; Pred = prednisolone; Inf = infliximab; Met = methotrexate; no BD meds = no systemic BD‐associated medication. Patients on infliximab (n = 1) and methotrexate (n = 1) were excluded in evaluation of effect on NK cells due to only single individuals in each of these subgroups. Numbers in parentheses above each bar indicate number of individuals in each comparison group.
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cei12939-fig-0004: Natural killer (NK) cell peripheral blood percentage is reduced significantly in patients under azathioprine therapy. (a) NK cells expressed as a percentage of total gated lymphocytes was compared in patients on different forms of Behçet's disease (BD) medication; colchicine (BDCol), prednisolone (BDPred), mycophenolate mofetil (BDMMF) and azathioprine (BDAza) and compared to healthy controls (HC) as well as patients not currently taking BD‐associated medication (BDNo therapy). (b) NK cell percentage expressed as a percentage of total lymphocytes in BD patients subgrouped according to disease activity (BDQuiet/Active) and whether currently taking azathioprine or not (BDAza or BDNon‐Aza). *P < 0·05; **P < 0·001; ***P < 0·001. Aza = azathioprine; Col = colchicine; MMF = mycophenolate mofetil; Pred = prednisolone; Inf = infliximab; Met = methotrexate; no BD meds = no systemic BD‐associated medication. Patients on infliximab (n = 1) and methotrexate (n = 1) were excluded in evaluation of effect on NK cells due to only single individuals in each of these subgroups. Numbers in parentheses above each bar indicate number of individuals in each comparison group.

Mentions: In order to determine whether NK cell depletion was due to disease activity or as a result of specific immunomodulatory medication, the BD cohort was subdivided according to current systemic BD drug therapy (azathioprine, colchicine, prednisolone and mycophenolate mofetil). The effect of these medications (when used as single/monotherapy) on NK percentage was compared with both HCs and non‐medicated BD patients (Fig. 4a).


Circulating NK cells and their subsets in Beh ç et's disease
Natural killer (NK) cell peripheral blood percentage is reduced significantly in patients under azathioprine therapy. (a) NK cells expressed as a percentage of total gated lymphocytes was compared in patients on different forms of Behçet's disease (BD) medication; colchicine (BDCol), prednisolone (BDPred), mycophenolate mofetil (BDMMF) and azathioprine (BDAza) and compared to healthy controls (HC) as well as patients not currently taking BD‐associated medication (BDNo therapy). (b) NK cell percentage expressed as a percentage of total lymphocytes in BD patients subgrouped according to disease activity (BDQuiet/Active) and whether currently taking azathioprine or not (BDAza or BDNon‐Aza). *P < 0·05; **P < 0·001; ***P < 0·001. Aza = azathioprine; Col = colchicine; MMF = mycophenolate mofetil; Pred = prednisolone; Inf = infliximab; Met = methotrexate; no BD meds = no systemic BD‐associated medication. Patients on infliximab (n = 1) and methotrexate (n = 1) were excluded in evaluation of effect on NK cells due to only single individuals in each of these subgroups. Numbers in parentheses above each bar indicate number of individuals in each comparison group.
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cei12939-fig-0004: Natural killer (NK) cell peripheral blood percentage is reduced significantly in patients under azathioprine therapy. (a) NK cells expressed as a percentage of total gated lymphocytes was compared in patients on different forms of Behçet's disease (BD) medication; colchicine (BDCol), prednisolone (BDPred), mycophenolate mofetil (BDMMF) and azathioprine (BDAza) and compared to healthy controls (HC) as well as patients not currently taking BD‐associated medication (BDNo therapy). (b) NK cell percentage expressed as a percentage of total lymphocytes in BD patients subgrouped according to disease activity (BDQuiet/Active) and whether currently taking azathioprine or not (BDAza or BDNon‐Aza). *P < 0·05; **P < 0·001; ***P < 0·001. Aza = azathioprine; Col = colchicine; MMF = mycophenolate mofetil; Pred = prednisolone; Inf = infliximab; Met = methotrexate; no BD meds = no systemic BD‐associated medication. Patients on infliximab (n = 1) and methotrexate (n = 1) were excluded in evaluation of effect on NK cells due to only single individuals in each of these subgroups. Numbers in parentheses above each bar indicate number of individuals in each comparison group.
Mentions: In order to determine whether NK cell depletion was due to disease activity or as a result of specific immunomodulatory medication, the BD cohort was subdivided according to current systemic BD drug therapy (azathioprine, colchicine, prednisolone and mycophenolate mofetil). The effect of these medications (when used as single/monotherapy) on NK percentage was compared with both HCs and non‐medicated BD patients (Fig. 4a).

View Article: PubMed Central - PubMed

ABSTRACT

Beh&ccedil;et'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/CD56Bright 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)&#8208;&gamma;, 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&thinsp;&lt;&thinsp;0&middot;0001) and their constituent CD56Dim (P&thinsp;&lt;&thinsp;0&middot;0001) and CD56Bright (P&thinsp;=&thinsp;0&middot;0015) subsets were depleted significantly in BD patients compared to HCs, and especially in those with active disease (BDActive) (P&thinsp;&lt;&thinsp;0&middot;0001). BD patients taking azathioprine also had significantly depleted NK cells compared to HCs (P&thinsp;&lt;&thinsp;0&middot;0001). A stepwise multivariate linear regression model confirmed BD activity and azathioprine therapy as significant independent predictor variables of peripheral blood NK percentage (P&thinsp;&lt;&thinsp;0&middot;001). In general, CD56Dim cells produced more perforin (P&thinsp;&lt;&thinsp;0&middot;0001) and granzyme B (P&thinsp;&lt;&thinsp;0&middot;01) expressed higher CD16 levels (P&thinsp;&lt;&thinsp;0&middot;0001) compared to CD56Bright cells, confirming their increased cytotoxic potential with overall higher NK cell CD107a expression in BD compared to HCs (P&thinsp;&lt;&thinsp;0&middot;01). Interestingly, IFN&#8208;&gamma; production and CD27 expression were not significantly different between CD56Dim/CD56Bright subsets. In conclusion, both BD activity and azathioprine therapy have significant independent depletive effects on the peripheral blood NK cell compartment.

No MeSH data available.


Related in: MedlinePlus