Disease markers · 2014
Abnormal expression pattern of the IL-2 receptor β-chain on CD4+ T cells in ANCA-associated vasculitis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wilde Benjamin, Hoerning André, Kribben Andreas, Witzke Oliver, Dolff Sebastian
Аннотация
BACKGROUND/AIM: ANCA-associated vasculitis (AAV) is a small-vessel vasculitis of autoimmune origin. In addition to autoantibodies, T cells have a pivotal pathophysiological role in this disease. T-cell homeostasis and immune tolerance critically depend on IL-2 and its receptor expressed by T cells. In this study, we investigated the IL-2 receptor (IL-2r) expression on CD4(+) T cells in AAV.
METHODS: Thirty patients with AAV and 15 age-matched healthy controls (HC) were enrolled. T cells from peripheral blood were analysed by flow cytometry for expression of the IL-2r α - and β-chain.
RESULTS: The IL-2r α-chain was overexpressed in AAV as compared to HC (36 ± 16% versus 20 ± 9%, P < 0.005). The IL-2r-β-chain expression was significantly reduced on CD25(+) CD4(+) T-cells and CD4(+)CD25(+)FoxP3(pos) regulatory T-cells (Tregs; AAV versus HC: 48 ± 14% versus 62 ± 9%, P = 0.002 and 38 ± 18% versus 68 ± 5%, P = 0.002). Low β -chain expression in AAV was associated with relapsing disease and systemic vasculitis with renal involvement.
CONCLUSION: The IL-2r expression pattern is abnormal in AAV. To our knowledge, we are the first to show that the β -chain expression is drastically diminished on T cells in AAV and related to a less favorable disease course. Given the indispensable function of the β -chain in IL-2 signaling of T cells, diminished expression may contribute to disturbed immune homeostasis in AAV.
METHODS: Thirty patients with AAV and 15 age-matched healthy controls (HC) were enrolled. T cells from peripheral blood were analysed by flow cytometry for expression of the IL-2r α - and β-chain.
RESULTS: The IL-2r α-chain was overexpressed in AAV as compared to HC (36 ± 16% versus 20 ± 9%, P < 0.005). The IL-2r-β-chain expression was significantly reduced on CD25(+) CD4(+) T-cells and CD4(+)CD25(+)FoxP3(pos) regulatory T-cells (Tregs; AAV versus HC: 48 ± 14% versus 62 ± 9%, P = 0.002 and 38 ± 18% versus 68 ± 5%, P = 0.002). Low β -chain expression in AAV was associated with relapsing disease and systemic vasculitis with renal involvement.
CONCLUSION: The IL-2r expression pattern is abnormal in AAV. To our knowledge, we are the first to show that the β -chain expression is drastically diminished on T cells in AAV and related to a less favorable disease course. Given the indispensable function of the β -chain in IL-2 signaling of T cells, diminished expression may contribute to disturbed immune homeostasis in AAV.