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Wang, Y.* ; Xiao, Y.* ; Zhong, L.* ; Ye, D.* ; Zhang, J.* ; Tu, Y.* ; Bornstein, S.R.* ; Zhou, Z.* ; Lam, K.S.* ; Xu, A.*

Increased neutrophil elastase and proteinase 3 and augmented NETosis are closely associated with β-cell autoimmunity in patients with type 1 diabetes.

Diabetes 63, 4239-4248 (2014)
DOI Order publishers version
Open Access Green as soon as Postprint is submitted to ZB.
Type 1 diabetes (T1D) is an autoimmune disease resulting from the self-destruction of insulin-producing β-cells. Reduced neutrophil counts have been observed in patients with T1D. However, the pathological roles of neutrophils in the development of T1D remain unknown. Here we show that circulating protein levels and enzymatic activities of neutrophil elastase (NE) and proteinase 3 (PR3), both of which are neutrophil serine proteases stored in neutrophil primary granules, were markedly elevated in patients with T1D, especially those with disease duration of less than 1 year. Furthermore, circulating NE and PR3 levels increased progressively with the increase of the positive numbers and titers of the autoantibodies against β-cell antigens. An obvious elevation of NE and PR3 was detected even in those autoantibody-negative patients. Increased NE and PR3 in T1D patients are closely associated with elevated formation of neutrophil extracellular traps. By contrast, the circulating levels of α1-antitrypsin, an endogenous inhibitor of neutrophil serine proteases, are decreased in T1D patients. These findings support an early role of neutrophil activation and augmented neutrophil serine proteases activities in the pathogenesis of β-cell autoimmunity and also suggest that circulating NE and PR3 may serve as sensitive biomarkers for the diagnosis of T1D.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 63, Issue: 12, Pages: 4239-4248 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)