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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

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

  • Margareta Budner1
  • Kamil Torres1
  • Violetta Opoka-Winiarska2
  • Agnieszka Lasota3
  • Małgorzata Gdak4
  • Paulina Mertowska5
  • Sebastian Mertowski5
  • Krzysztof Gosik5
  • Minseung Kang6
  • Tomasz Urbanowicz7,8
  • Ewelina Grywalska5
8 affiliations
  1. 1Department of Plastic, Reconstructive and Microsurgery, Medical University of Lublin, ul. Jaczewskiego 8, 20-090 Lublin, Poland
  2. 2Department of Pediatric Pulmonology and Rheumatology, Medical University of Lublin, ul. Prof. Antoniego Gębali 6, 20-093 Lublin, Poland
  3. 3Department of Jaw Orthopaedics, Medical University of Lublin, ul. Chodźki 6, 20-093 Lublin, Poland
  4. 4Department of Pediatric Pulmonology and Rheumatology, University Children’s Hospital, ul. Prof. Antoniego Gębali Street 6, 20-093 Lublin, Poland
  5. 5Department of Experimental Immunology, Medical University of Lublin, ul. Chodźki 4a, 20-093 Lublin, Poland
  6. 6College of Medicine, Korea University, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
  7. 7Cardiac Surgery and Transplantology Department, Poznan University of Medical Sciences, ul. Długa 1/2, 61-848 Poznań, Poland
  8. 8Department of Precision Medicine in Medical Surgical and Critical Area, University of Palermo, 90134 Palermo, Italy
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{budner2026checkpoint,
  title = {{Checkpoint Pathways in Childhood Cleft Lip and Palate—Associations of PD1 and CTLA4 with Clinical Parameters}},
  author = {Margareta Budner and Kamil Torres and Violetta Opoka-Winiarska and Agnieszka Lasota and Małgorzata Gdak and Paulina Mertowska and Sebastian Mertowski and Krzysztof Gosik and Minseung Kang and Tomasz Urbanowicz and Ewelina Grywalska},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219488},
  url = {https://www.mdpi.com/1422-0067/27/21/9488},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Checkpoint Pathways in Childhood Cleft Lip and Palate—Associations of PD1 and CTLA4 with Clinical Parameters
AU  - Margareta Budner
AU  - Kamil Torres
AU  - Violetta Opoka-Winiarska
AU  - Agnieszka Lasota
AU  - Małgorzata Gdak
AU  - Paulina Mertowska
AU  - Sebastian Mertowski
AU  - Krzysztof Gosik
AU  - Minseung Kang
AU  - Tomasz Urbanowicz
AU  - Ewelina Grywalska
PY  - 2026
DA  - 2026/10/24
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219488
UR  - https://www.mdpi.com/1422-0067/27/21/9488
AB  - 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.
SN  - 1422-0067
ER  -