Contribution of monocyte subpopulations to the pathogenesis and therapy outcome of type 1 diabetes management in pediatric patients.

Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by the destruction of pancreas β cells causing impairment in insulin secretion. Despite various factors contributing to T1D, i.e., immunological, genetic, and environmental factors, the exact pathomechanism of T1D remains still not fully understood. Monocytes, the heterogeneous population of immune cells, are the main stones in the innate immune mechanisms. Recently, monocytes have also been considered to be involved in promoting autoimmune disease. Here, our study aimed to evaluate the frequencies of monocyte subsets derived from peripheral blood mononuclear cells (PBMCs) in newly diagnosed pediatric T1D patients at the time of admission. Moreover, our study was followed by a simultaneous assessment of the association of immune parameters with clinically relevant data and disease outcomes. Firstly, we indicated the increased frequencies of intermediate monocytes in T1D patients compared with HC. Those monocytes also presented the increased expression of CD163 activation molecules. Furthermore, the frequency of intermediate monocytes was associated with the GADA autoantibody and the c-peptide levels. Initially increased percentages of intermediate monocytes were followed with higher changes for achieving the clinically relevant c-peptide after 2-year insulin treatment. Interestingly, initial levels of monocyte subsets seem to have no impact on the normalization of HbA1c during treatment; nevertheless, initiative higher frequencies of classical monocytes and lower frequencies of non-classical monocytes were accompanied by higher levels of HbA1c. In conclusion, our findings suggest that monocyte subsets are closely associated with the pathogenesis of T1D and that distinct subsets may have potential value in predicting therapy outcomes.