high basal activity of the ptpn22 gain-of-function variant blunts leukocyte responsiveness negatively affecting il-10 production in anca vasculitis高的基底活动ptpn22功能变体阻碍白细胞反应消极影响il - 10在anca生产血管炎.pdfVIP

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high basal activity of the ptpn22 gain-of-function variant blunts leukocyte responsiveness negatively affecting il-10 production in anca vasculitis高的基底活动ptpn22功能变体阻碍白细胞反应消极影响il - 10在anca生产血管炎.pdf

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high basal activity of the ptpn22 gain-of-function variant blunts leukocyte responsiveness negatively affecting il-10 production in anca vasculitis高的基底活动ptpn22功能变体阻碍白细胞反应消极影响il - 10在anca生产血管炎

High Basal Activity of the PTPN22 Gain-of-Function Variant Blunts Leukocyte Responsiveness Negatively Affecting IL-10 Production in ANCA Vasculitis 1¤ 1 1 1 1 1 Yali Cao , Jiajin Yang , Kerry Colby , Susan L. Hogan , Yichun Hu , Caroline E. Jennette , 1 3 2,1 1,2 1,2 Elisabeth A. Berg , Youkang Zhang , J. Charles Jennette , Ronald J. Falk , Gloria A. Preston * 1 Division of Nephrology and Hypertension, UNC Kidney Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 2 Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 3 Department of Medicine, Institute of Nephrology, Peking University First Hospital, Peking University, Beijing, People’s Republic of China Abstract Consequences of expression of the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gain-of-function variant were evaluated in leukocytes from patients with anti-neutrophil cytoplasmic autoantibody (ANCA) disease. The frequency of the gain-of-function allele within the Caucasian patient cohort was 22% (OR 1.45), compared to general American Caucasian population (16.5%, p = 0.03). Examination of the basal phosphatase activity of PTPN22 gain-of-function protein indicated persistently elevated activity in un-stimulated peripheral leukocytes, while basal activity was undetectable in leukocytes from patients without the gain-of-function variant. To examine consequences of persistently high PTPN22 activity, the activati