CD4(+) CD25(+) cells in type 1 diabetic patients with other autoimmune manifestations

Abstract

The existence of multiple autoimmune disorders in diabetics may indicate underlying primary defects of immune regulation. The study aims at estimation of defects of CD4(+) CD25(+high) cells among diabetic children with multiple autoimmune manifestations, and identification of disease characteristics in those children. Twenty-two cases with type 1 diabetes associated with other autoimmune diseases were recruited from the Diabetic Endocrine and Metabolic Pediatric Unit (DEMPU), Cairo University along with twenty-one normal subjects matched for age and sex as a control group. Their anthropometric measurements, diabetic profiles and glycemic control were recorded. Laboratory investigations included complete blood picture, glycosylated hemoglobin, antithyroid antibodies, celiac antibody panel and inflammatory bowel disease markers when indicated. Flow cytometric analysis of T-cell subpopulation was performed using anti-CD3, anti-CD4, anti-CD8, anti-CD25 monoclonal antibodies. Three cases revealed a proportion of CD4(+) CD25(+high) below 0.1% and one case had zero counts. However, this observation did not mount to a significant statistical difference between the case and control groups neither in percentage nor absolute numbers. Significant statistical differences were observed between the case and the control groups regarding their height, weight centiles, as well as hemoglobin percentage, white cell counts and the absolute lymphocytic counts. We concluded that, derangements of CD4(+) CD25(+high) cells may exist among diabetic children with multiple autoimmune manifestations indicating defects of immune controllers.

Keywords: Autoimmunity; CD4+ CD25+ cells; Children; T regulatory cells; Type1 diabetes mellitus.

Fig. 1

Comparison between cases and control groups regarding their height on the Egyptian growth chart (percentiles).

Fig. 2

Comparison of the absolute number of CD3⁺ CD4⁺ in cases and control group.

Fig. 3

Flow cytometric results of patient 14: The lymphocyte, as it was identified by their forward and side scatter properties were gated for coexpression of CD4⁺ and CD25^+high. CD4⁺CD25^+high = 0%.

Fig. 4

By analyzing the Roc curve of absolute CD4⁺ CD25^+high it did not achieve under the curve >65% and it was of no significant P-value.

Fig. 5

Whisker and box plot comparison of the absolute counts of CD4⁺ CD25^+high in both cases and control groups.

Fig. 6

Flow cytometric results of patient 9: The lymphocyte, as it was identified by their forward and side scatter properties were gated (a) for co expression of CD4⁺ and CD25^+high. CD4⁺CD25^+high = 0.09% (b) compared to one of the healthy controls (c and d) where the CD4⁺CD25^+high = 1.37%.