Checkpoint Pathways in Childhood Cleft Lip and Palate—Associations of PD1 and CTLA4 with Clinical Parameters

Cleft lip and/or palate (CL/P) is associated with recurrent upper respiratory tract complications, yet the immunoregulatory mechanisms accompanying this defect remain insufficiently understood. This study aimed to characterize cellular and soluble parameters associated with PD-1, PD-L1, and CTLA-4 in children with CL/P and to analyze their associations with selected clinical and hematological characteristics. This single-center cross-sectional study included 32 children with CL/P and 16 healthy children as controls. Serum concentrations of sPD-1, sPD-L1, and sCTLA-4 were measured, and the percentages of cells expressing PD-1, PD-L1, and CTLA-4 within T-lymphocyte (CD3+ CD4+ and CD3+ CD8+) and B-lymphocyte (CD19+) populations were assessed using flow cytometry. We analyzed relationships between immunological and clinical parameters, as well as differences between subgroups by gender and mode of delivery. Children with CL/P exhibited significantly higher serum concentrations of sPD-1, sPD-L1, and sCTLA-4, as well as higher percentages of T and B lymphocytes expressing these immune checkpoint molecules, compared to the control group (p < 0.0001 in all cases). We observed significant associations among selected immune checkpoint-related parameters, including a positive correlation between sPD-1 and sCTLA-4 and an inverse correlation between the percentages of CD19+ PD-L1+ and CD19+ CTLA-4+ B lymphocytes. The markers clearly distinguished children with CL/P from healthy children in the study cohort; however, we found no consistent differences by gender or mode of delivery. Children with CL/P exhibited distinct cellular and soluble immune checkpoint-related profiles compared to the control group. However, given the limited sample size and the study’s cross-sectional design, these results should be considered preliminary and require confirmation in larger, independent cohorts.