case_images: PMC11363706_01
case_images: The C129S missense mutation dramatically impairs CTLA-4 expression resulting in decreased transendocytosis. (A) Representative example of CD80GFP transendocytosis assay results. These plots show cells previously gated on forward and side scatter profile, and negative for Cell Trace Violet. GFP signal represents percent transendocytosis of CD80. (B) Summary results from n = 3 independent experiments, performed as in A. (C) Percent CTLA-4+ CHO cells after transfection with WT or mutant CTLA-4 plasmids (n = 3),**p < 0.01, unpaired t-tests. (D) Flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) to identify CD4 + FoxP3 + regulatory T-cells (T  regs) and CD4 + CD3- cells. (E) Analysis of CTLA-4 protein expression by Tregs (upper row) and CD4 + FoxP3 + cells (lower row), gated as shown in (D). (F) Mean fluorescence intensity for CTLA-4 on Tregs from two healthy donors, and the patient and his father with the C129S variant.
case_images: fped-12-1434076-g002.jpg
case_images: PMC11363706_01_fped-12-1434076-g002.jpg
case_images: F2
case_images: These findings are similar to those seen with the causal allele R51X (Figure 2). Moreover, analysis of peripheral blood mononuclear cells (PBMCs) from the patient and his father confirmed reduced CTLA-4 protein levels (Figures 2D,E).