Molecular investigations on T cell subsets in patients affected by hypomorphic DCLRE1C mutation

ABSTRACT

Objective

In this study, we explored the expression of transcription factors, cytokines, and co-stimulatory molecules within the helper T (Th) cell subsets (Th1, Th2, Th17, and Treg) of patients with hypomorphic DCLRE1C gene mutations.

Methods

The study comprised eight patients and five controls. Transcription factor and cytokine expressions of Th subsets and co-stimulatory molecules were investigated by qPCR and flow cytometric following T cell stimulation. The findings were compared between patients (non-HSCT) and with hematopoietic stem cell transplantation (HSCT).

Results

Flow cytometric analyses; while the Treg rate was significantly lower in non-HSCT than in controls (p = 0.010), the IFN-γ rate was significantly higher in patients than in the control and HSCT groups (p = 0.016, p = 0.022, respectively). Co-stimulatory molecule expressions were significantly lower in non-HSCT than in control (p < 0.001), and there was a significant improvement after HSCT. Post-stimulation qPCR analysis, significant changes were detected in non-HSCT/control, non-HSCT/HSCT, and HSCT/control comparisons.

Conclusions

Our study is the first study to molecularly investigate Th cell subsets in hypomorphic DCLRE1C patients. It was determined that abnormalities in Th cell subsets still persisted despite HSCT. There are still many conditions to be explained in these patients, and we believe that our study may shed light on future studies.

KEYWORDS:

• Leaky SCID
• DCLRE1C
• Th cell
• Treg
• CD4

Declaration of interest

The authors were supported by Necmettin Erbakan University Scientific Research Projects Coordinator. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Acknowledgments

We thank our patients who participated in the study and we thank to Necmettin Erbakan University the Scientific Research Committee for financial support (project number: 192018006).

Authors’ contributions

MA Karaselek and S Keles: conception and design; O Dogar, A Kıykım, E Hazar, S Guner, and I Reisli: evaluation of the patients; MA Karaselek, T Duran, and S Kuccukturk: molecular analysis and interpretation of the data; S Keles and MA Karaselek: flow cytometry analysis and interpretation of the data; S Guner and S Kuccukturk: statistical data analysis and interpretation; MA Karaselek: drafting of the paper; S Keles and I Reisli: revising the paper critically for intellectual content; S Keles and I Reisli: final approval of the version to be published; all authors agree to be accountable for all aspects of the study.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/1744666X.2024.2352479

Ethics statement

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by Necmettin Erbakan University Ethics Committee (approval number: 2023/4615).

Additional information

Funding

The study was funded by Necmettin Erbakan University Scientific Research Projects Coordinator for supporting the project [project number: 192018006].