Monocyte Soluble Activation Markers sCD14 and sCD163 in Children With Type 1 Diabetes Mellitus
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Children diagnosed to have T1DM with a minimum duration of five years
|
Diagnostic Test: ELISA
Determination of serum levels of sCD14 and sCD163 using ELISA
|
| Healthy children
|
Diagnostic Test: ELISA
Determination of serum levels of sCD14 and sCD163 using ELISA
|
Outcome Measures
Primary Outcome Measures
- To compare the levels of monocyte soluble activation markers among children with T1DM and healthy controls [Baseline]
To compare the levels of sCD14 and sCD163 among children with T1DM and healthy controls using ELISA
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assiut University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
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- Harms RZ, Ostlund KR, Cabrera MS, Edwards E, Fisher M, Sarvetnick N. Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes. Front Immunol. 2020 Sep 15;11:1922. doi: 10.3389/fimmu.2020.01922. eCollection 2020.
- Ismail NA, Abd El Baky AN, Ragab S, Hamed M, Hashish MA, Shehata A. Monocyte chemoattractant protein 1 and macrophage migration inhibitory factor in children with type 1 diabetes. J Pediatr Endocrinol Metab. 2016 Jun 1;29(6):641-5. doi: 10.1515/jpem-2015-0340.
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- Marshak-Rothstein A. Autoimmunity--promoting and stabilizing innate immunity 'UNWUCHT'. Immunol Rev. 2016 Jan;269(1):7-10. doi: 10.1111/imr.12387.
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- Myśliwska J, Smardzewski M, Marek-Trzonkowska N, Myśliwiec M, Raczyńska K. Expansion of CD14+CD16+ monocytes producing TNF-α in complication-free diabetes type 1 juvenile onset patients. Cytokine. 2012 Oct;60(1):309-17. doi: 10.1016/j.cyto.2012.03.010. Epub 2012 Apr 7.
- Ratajczak W, Atkinson SD, Kelly C. The TWEAK/Fn14/CD163 axis-implications for metabolic disease. Rev Endocr Metab Disord. 2022 Jun;23(3):449-462. doi: 10.1007/s11154-021-09688-4. Epub 2021 Sep 20. Review.
- Wong KL, Tai JJ, Wong WC, Han H, Sem X, Yeap WH, Kourilsky P, Wong SC. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood. 2011 Aug 4;118(5):e16-31. doi: 10.1182/blood-2010-12-326355. Epub 2011 Jun 7.
- Monocyte activation markers