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Article: Increased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes

TitleIncreased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes
Authors
Issue Date2014
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2014, v. 63 n. 12, p. 4239-4248 How to Cite?
AbstractType 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.
Persistent Identifierhttp://hdl.handle.net/10722/211512
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185

 

DC FieldValueLanguage
dc.contributor.authorWang, Y-
dc.contributor.authorXiao, Y-
dc.contributor.authorZhong, L-
dc.contributor.authorYe, D-
dc.contributor.authorZhang, J-
dc.contributor.authorTu, Y-
dc.contributor.authorBornstein, SR-
dc.contributor.authorZhou, Z-
dc.contributor.authorLam, KSL-
dc.contributor.authorXu, A-
dc.date.accessioned2015-07-16T02:33:07Z-
dc.date.available2015-07-16T02:33:07Z-
dc.date.issued2014-
dc.identifier.citationDiabetes, 2014, v. 63 n. 12, p. 4239-4248-
dc.identifier.issn0012-1797-
dc.identifier.urihttp://hdl.handle.net/10722/211512-
dc.description.abstractType 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.-
dc.languageeng-
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/-
dc.relation.ispartofDiabetes-
dc.rightsThis is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes [http://diabetes.diabetesjournals.org/]. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is available online at http://diabetes.diabetesjournals.org/content/63/12/4239.long-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleIncreased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes-
dc.typeArticle-
dc.identifier.emailYe, D: deweiye@hku.hk-
dc.identifier.emailZhang, J: hjzhang@hkucc.hku.hk-
dc.identifier.emailLam, KSL: ksllam@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityLam, KSL=rp00343-
dc.identifier.authorityXu, A=rp00485-
dc.description.naturepostprint-
dc.identifier.doi10.2337/db14-0480-
dc.identifier.pmid25092677-
dc.identifier.hkuros244398-
dc.identifier.volume63-
dc.identifier.issue12-
dc.identifier.spage4239-
dc.identifier.epage4248-
dc.publisher.placeUnited States-

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