LAUSR

We would like to respond to the stimulating commentary by Dr. Bonaventura and Dr. Montecucco [1] on our article ‘Characterization of circulating leukocytes and correlation of leukocyte subsets with metabolic parameters 1 and 5 years after diabetes diagnosis’. These authors not only elegantly summarize the main results of our study [2], but also discuss accumulating data on the role of neutrophils in the pathogenesis of type 1 diabetes (T1D). Recently, peripheral neutropenia has been proposed to precede and accompany the onset of T1D, mainly resulting from increased infiltration of small pancreatic blood vessels by neutrophils [3]. Neutrophils—a rather unexplored player in T1D pathogenesis—could initiate T-cell response and promote T1D development, indicative of a crosstalk between innate and adaptive immunity in the early stages of T1D, as summarized by recent studies [4, 5]. Our new data reveal that in a rather large, comprehensively phenotyped cohort, neutrophil count was already lower in T1D than in type 2 diabetes patients at the time of clinical diabetes diagnosis, but also at 5 years after diabetes diagnosis [2]. Also, neutrophil count correlated positively with C-peptide levels at 5 years of T1D duration, suggesting the presence of more profound neutropenia among patients with very low β-cell secretory capacity. We agree that the role of innate immunity and the crosstalk with the adaptive immune system will require detailed future studies not only for the better understanding of pathogenic mechanisms of T1D, but also for examining, whether neutrophils may serve as a marker for prediction of disease onset and—as supported by our study—of disease progression and β-cell secretory capacity during the years after T1D diagnosis. Author contributions MA wrote the response and MR read and critically reviewed the response.