Reduction of circulating neutrophils precedes and accompanies type 1 diabetes.
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.
San Raffaele Scientific Institute, Diabetes Research Institute, Milan, Italy.
Andrea
A
Valle
Gian Maria
GM
Giamporcaro
Marina
M
Scavini
Angela
A
Stabilini
Pauline
P
Grogan
Eleonora
E
Bianconi
Guido
G
Sebastiani
Matilde
M
Masini
Norma
N
Maugeri
Laura
L
Porretti
Riccardo
R
Bonfanti
Franco
F
Meschi
Maurizio
M
De Pellegrin
Arianna
A
Lesma
Silvano
S
Rossini
Lorenzo
L
Piemonti
Piero
P
Marchetti
Francesco
F
Dotta
Emanuele
E
Bosi
Manuela
M
Battaglia
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000648:ultrastructure; D055815:Young Adult
D001323:Autoantibodies