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 language | English |
|---|---|
| Pages (from-to) | 2072-2077 |
| Number of pages | 6 |
| Journal | Diabetes |
| Volume | 62 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2013 |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
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Reduction of circulating neutrophils precedes and accompanies type 1 diabetes. / Valle, Andrea; Giamporcaro, Gian Maria; Scavini, Marina; Stabilini, Angela; Grogan, Pauline; Bianconi, Eleonora; Sebastiani, Guido; Masini, Matilde; Maugeri, Norma; Porretti, Laura; Bonfanti, Riccardo; Meschi, Franco; De Pellegrin, Maurizio; Lesma, Arianna; Rossini, Silvano; Piemonti, Lorenzo; Marchetti, Piero; Dotta, Francesco; Bosi, Emanuele; Battaglia, Manuela.
In: Diabetes, Vol. 62, No. 6, 06.2013, p. 2072-2077.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Reduction of circulating neutrophils precedes and accompanies type 1 diabetes
AU - Valle, Andrea
AU - Giamporcaro, Gian Maria
AU - Scavini, Marina
AU - Stabilini, Angela
AU - Grogan, Pauline
AU - Bianconi, Eleonora
AU - Sebastiani, Guido
AU - Masini, Matilde
AU - Maugeri, Norma
AU - Porretti, Laura
AU - Bonfanti, Riccardo
AU - Meschi, Franco
AU - De Pellegrin, Maurizio
AU - Lesma, Arianna
AU - Rossini, Silvano
AU - Piemonti, Lorenzo
AU - Marchetti, Piero
AU - Dotta, Francesco
AU - Bosi, Emanuele
AU - Battaglia, Manuela
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878259455&partnerID=8YFLogxK
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U2 - 10.2337/db12-1345
DO - 10.2337/db12-1345
M3 - Article
C2 - 23349491
AN - SCOPUS:84878259455
VL - 62
SP - 2072
EP - 2077
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 6
ER -