Reduction of circulating neutrophils precedes and accompanies type 1 diabetes

Andrea Valle, Gian Maria Giamporcaro, Marina Scavini, Angela Stabilini, Pauline Grogan, Eleonora Bianconi, Guido Sebastiani, Matilde Masini, Norma Maugeri, Laura Porretti, Riccardo Bonfanti, Franco Meschi, Maurizio De Pellegrin, Arianna Lesma, Silvano Rossini, Lorenzo Piemonti, Piero Marchetti, Francesco Dotta, Emanuele Bosi, Manuela Battaglia

Research output: Contribution to journalArticlepeer-review

Abstract

Human type 1 diabetes (T1D) is an autoimmune disease associated with major histocompatibility complex polymorphisms, β-cell autoantibodies, and autoreactive T cells. However, there is increasing evidence that innate cells may also play critical roles in T1D. We aimed to monitor peripheral immune cells in early stages of T1D (i.e., in healthy autoantibody-positive subjects) and in more advanced phases of the disease (i.e., at disease onset and years after diagnosis). We found a mild but significant and reproducible peripheral neutropenia that both precedes and accompanies the onset of T1D. This reduction was not due to peripheral neutrophil cell death, impaired differentiation, or the presence of anti-neutrophil antibodies. Neutrophils were observed by electron microscopy and immunohistochemical analysis in the exocrine pancreas of multiorgan donors with T1D (both at onset and at later stages of the disease) and not in that of multiorgan donors with type 2 diabetes or nondiabetic donors. These pancreas-infiltrating neutrophils mainly localized at the level of very small blood vessels. Our findings suggest the existence of a hitherto unrecognized clinical phenotype that might reflect unexplored pathogenic pathways underlying T1D.

Original languageEnglish
Pages (from-to)2072-2077
Number of pages6
JournalDiabetes
Volume62
Issue number6
DOIs
Publication statusPublished - Jun 2013

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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