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Published on: May 6, 2013
High expression of OX40 (CD134) and 4-1BB (CD137) molecules on CD4(+)CD25(high) cells in children with type 1
Agnieszka Szypowska1, Anna Stelmaszczyk-Emmel2, Urszula Demkow2
1Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland.
Insights
This study found higher levels of OX40 and 4-1BB positive cells in children with type 1 diabetes (T1D), particularly in those under 5 years old. These findings suggest a role for these immune cells in T1D pathogenesis in pediatric populations.
Area of Science:
- Immunology
- Pediatric Endocrinology
- Diabetes Research
Background:
- Type 1 diabetes (T1D) incidence is rising in children, especially those under 5.
- Mechanisms of beta-cell damage in pediatric T1D are not well understood.
- Immune cell involvement in T1D pathogenesis requires further investigation.
Purpose of the Study:
- To compare the frequency of OX40 (CD134) and 4-1BB (CD137) positive cells in the peripheral blood of children with newly diagnosed T1D versus healthy controls.
- To investigate potential age-related differences in these immune cell populations, focusing on children under 5 years of age.
Main Methods:
- Flow cytometry was used to analyze peripheral blood samples from 33 children with newly diagnosed T1D and 39 healthy controls.
- Key markers analyzed included CD4, CD25, CD137 (4-1BB), and CD134 (OX40).
- Fasting C-peptide levels were measured, and separate analyses were conducted for children under 5 years old.
Main Results:
- Children with T1D showed a significantly higher frequency of CD4(+)CD25(high)OX40(+) cells (3.58% vs. 1.1%, p=0.003) and CD4(+)CD25(high)4-1BB(+) cells (5.76% vs. 3.74%, p=0.037) compared to controls.
- A positive correlation was observed between the age of diabetic children and their C-peptide levels (r=0.54, p=0.004).
- Children under 5 with T1D exhibited a higher frequency of both CD4(+)CD25(high)OX40(+) (p=0.004) and CD4(+)CD25(high)4-1BB(+) cells (p=0.079) compared to age-matched controls.
Conclusions:
- The frequency of OX40 and 4-1BB positive immune cells is elevated in children with T1D compared to healthy children.
- These immune cell differences may be more pronounced in younger children (under 5 years).
- Further research is necessary to elucidate age-related immune system variations and their role in T1D pathogenesis.
Purpose:
Despite the rapidly rising incidence of diabetes in children, with the highest rise in children<5 years of age, data on mechanisms that trigger severe beta-cells damage are limited. The aim of the study was to assess the frequency of OX40 (CD134) or 4-1BB (CD137) positive cells in the peripheral blood of children with newly diagnosed type 1 diabetes (T1D) in comparison to healthy controls.
Material/Methods:
The study included 33 children (mean age 7.3 ± 5.4 years) with newly diagnosed T1D and 39 age-matched healthy controls. Separate analysis was performed in children<5 years. Flow cytometric analysis was performed using the following markers: CD4, CD25, CD137, and CD134. Fasting C-peptide level was assessed as well.
Results:
The frequency of CD4(+)CD25(high)OX40(+) was higher in T1D children than in controls (median value 3.58% vs. 1.1%, respectively; p=0.003). Moreover, T1D children had higher frequency of CD4(+)CD25(high)4-1BB(+) cells than healthy subjects (median value 5.76% vs. 3.74%, respectively; p=0.037). A significant correlation was noted between the age of diabetic children and the C-peptide level (r=0.54, 95% CI [0.19-0.77], p=0.004). In comparison with age-matched controls, children<5 years had higher frequency of CD4(+)CD25(high)OX40(+) (p=0.004) and CD4(+)CD25(high)4-1BB(+) cells (p=0.079).
Conclusions:
Our study showed higher frequency of both OX40 and 4-1BB positive cells in T1D children in comparison to controls. It seems that observed differences might be more pronounced in children<5 years of age than in older subjects. Further clinical studies are needed to determine the age-related differences in the immune system, in the pathogenesis of T1D.
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