علاقة خلايا البائية المنظمة وبعض المؤشرات المناعية باصابات الجهاز البولي في مرضى السكري من النوع الاول

Association of B-reg Frequency and Some Immunological Parameters with Urinary Tract Infections in Type 1 Diabetes

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by lack of insulin and destruction of pancreatic β cells. Autoimmune reaction is a key step during the progression of T1DM, where T-cells play a vital role. However; B-cells also play important role in the occurrence and development of T1DM. The B-cells producing Interleukin-10 (IL-10) have been labeled as regulatory B-cells (B-reg). Diabetes and bacterial infections are linked in both directions. Chronic infections are associated with higher proinflammatory cytokines, which can exacerbate insulin resistance and compromise glycemic management, whereas diabetes increases susceptibility to bacterial infections and their consequences. There is growing proof that changes in the microbiota’s makeup that may have a significant impact on how diabetes develops. The current study aimed to consolidate and update the current knowledge about the cellular and regulatory molecules that are exhibited by B-reg for T1DM patients and the role of the disease in the development of urinary tract infection (UTI).
The current investigation was carried out in the provinces of Kerbala. A total of 90 male children blood and urine samples were collected, whose ages ranged between 5-15 years. 60 patients with T1DM (30 T1DM patients with UTIs and 30 T1DM patients without UTIs) and 30 healthy individuals (control group). The frequency of B-cell subsets were measured using flow cytometry and cultivation urine on agar to indicate UTIs. The level of human serum of some immunological markers was measured by ELISA assay.
The results of the current study showed that a significant decreased the percentage of cluster of differentiation (CD)19+B cells on level P ≤ 0.0001 for both patients groups of T1DM compared to control . CD19+IL10+ B-cell (B-reg) was significant decreased in T1DM with UTIs compared with healthy controls but increased in the group of T1DM without UTIs. T1DM with UTIs significantly increased CD80 expression on B-reg, whereas T1DM without UTIs only slightly decreased it when compared to the control group. Additionally, it demonstrated that in both groups of T1DM patients, the concentration of CD80 expression on B-reg has significantly decreased.

IL-35, macrophage migration inhibitory factor (MIF), Lipopolysaccharide binding protein (LBP) and Toll-like receptors (TLR4) were higher for both patients groups of T1DM compared to control group but more significant increase in barameters levels for T1DM with bacterial infection compared with both other groups. Transforming growth factor-β (TGF-β1) level was higher in T1DM with UTIs compared with patients without bacterial infection and healthy individuals.
The bacterial infections lead to an increase in the plasma level of total cholesterol (CHOL), total to high-density lipoprotein cholesterol (TC/HDL-C) , Low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (Non-HDL-C) compared to diabetic patients without UTIs and healthy individuals. Triglyceride (TC) concentration was significantly higher in diabetic patients without bacterial infection compared to T1DM with UTIs and healthy individuals.
The concentration of serum aspartate transaminase (AST) and alanine transaminase (ALT) were significantly decreasing in T1DM in comparison with controls. The concentration of alkaline phosphatase (ALP) were significantly elevated in diabetic patients without UTIs compared to T1DM with UTIs and controls. A significant increases are in the levels of total serum bilirubin and creatinine in T1DM with UTIs when compared to controls and T1DM without UTIs.
The bacterial pathogens that cause UTI belong to gram negative 54% and gram-positive bacteria 46%. Among Gram negative pathogens, Escherichia coli is the principal etiology of UTI in diabetic individuals that estimated at 35% followed by Pseudomonas stutzeria while among Gram positives, Kocuria rosea is the major uropathogen estimated at 18.5 % followed by Streptococcus thoraltensis , Streptococcus gallolyticus , Staphylococcus haemolyticus , Kocuria kristinae.

These findings suggest that numerically deficient for CD19+B cells ,CD19+IL10+ B-cell and CD19+IL10+CD24+CD27+ B-reg percentage in B-cell and difference in the cytokines concentration for T1DM children with bacterial infection, that may involve in the loss of auto-tolerance of immunity system that ensuing death of pancreatic beta cells, making it a viable immunotherapy target.