The study aims to compare serum levels of sCD14 and sCD163 in children with type 1 Diabetes Mellitus with healthy controls, study the distribution of monocyte subsets in children with T1DM , correlate monocyte subsets and their soluble activation markers sCD14 and sCD163 with parameters reflecting islet β-cell insufficiency in children with T1DM.

Type 1 diabetes mellitus (T1DM) is T-cell mediated autoimmune disease in which the function of insulin-secreting pancreatic β-cells is impaired due to autoreactive immune cell-mediated destruction (insulitis). Although adaptive immunity has always been the focus for scientists in studying the pathogenesis of T1DM, yet, innate immunity also plays a critical role. Alterations in innate immune responses drive autoimmune pathogenesis, with involvement in the initial break in tolerance and the later failure of regulation. Several studies suggest that the development of T1DM is strongly associated with different immune cells, including monocytes. Specifically, an increase in the monocyte population has been shown to trigger β-cell destruction during insulitis. Intermediate monocytes may serve as M2 macrophage precursors with high anti-inflammatory properties, producing IL-10. However, other studies reported them to have an antigen-presenting function with a dendritic cell-like feature. Upon antigen stimulation, they became the main producers of inflammatory factors, like TNF-α which has been shown to correlate with the severity of T1DM. Activation of circulating monocytes to a pro-inflammatory state induces the shedding of membrane bound CD14 (mCD14) to soluble CD14. Compared to other acute phase proteins, sCD14 was found to be the most sensitive in T1DM. Soluble CD163 is present in blood serum as a result of shedding the CD163 membrane form of activated monocyte-macrophage-lineage cells in the course of inflammation. Plasma sCD163 is widely used as an immunomodulator with anti-inflammatory properties. It was found to be increased in T2DM.

Inclusion Criteria:

• Children of any age and sex diagnosed with T1DM (according to WHO criteria) with a minimum duration of five years will be included.

Exclusion Criteria:

• Children with other with coexisting autoimmune, chronic, and acute inflammatory diseases.

Children with type 1 Diabetes Mellitus Pediatric Endocrinology Unit in Assiut University Children Hospital