DETERMINING PARTICIPATION PERIPHERAL BLOOD B-CELLS, B-REG CELLS, AND MEMORY B-REG CELLS IN DIABETES MELLITUS TYPE Ι DISEASE AND THE EFFECT OF THE URINARY TRACT INFECTION RESPONSE

Background. Type 1 diabetes mellitus (T1DM) is a complex autoimmune disorder. Despite the crucial anti-inflammatory role of IL-10-secreting memory regulatory B cells (memory Bregs), their specific profile and function in T1DM remain poorly understood.The aim of the study was to investigate the peripheral blood frequencies of total B cells, regulatory B cells (Bregs), and memory Breg cells (CD19+IL-10+ CD24^hi CD27+) in patients with Type 1 Diabetes Mellitus (T1DM). Furthermore, the study aimed to evaluate the impact of concurrent urinary tract infections (UTIs) on these immune profiles by comparing T1DM patients with and without UTIs to healthy controls, thereby elucidating the interplay between bacterial infections, Breg cell depletion, and T1DM pathogenesis. Materials and methods. This case-control study evaluated male children T1DM patients, categorized by the presence or absence of concurrent UTIs, alongside a healthy control group. Flow cytometry was utilized to quantify the frequencies of total B cells and memory Bregs subsets. Additionally, clinical markers including glutamic acid decarboxylase autoantibodies (GADA) and C-peptide levels were assessed. Results. A significant decrease in total B cells and overall regulatory B cells was observed among T1DM patients, particularly those with concurrent UTIs. Notably, memory Bregs exhibited a significant stepwise decline: dropping from 47.07% in healthy controls to 26.97% in T1DM patients without UTIs, and further decreasing to 21.98% in those with UTIs. Coupled with elevated GADA and diminished C-peptide levels, these findings demonstrate that bacterial infections significantly exacerbate the depletion of regulatory B cell subsets. Conclusion. The profound depletion of total B, Breg, and memory Breg cells in T1DM children exacerbated by concurrent bacterial infections critically drives the loss of immune tolerance and β-cell destruction. Therefore, restoring memory Breg function offers a promising immunotherapeutic strategy for T1DM.