IL-12Rβ1 deficiency corresponding to concurrency of two diseases, mendelian susceptibility to mycobacterial disease and Crohn's disease.

Background: The interleukin-12 receptor β1 (IL-12Rβ1) deficiency is a primary immunodeficiency (PID), affecting the immunological pathway of interleukin 12/interferon- γ (IL12/IFN-γ) axis and interleukin 23 receptor (IL23R). Defect in this pathway is mainly affecting the cellular immunity-related disorders. IL-12Rβ1 is a receptor chain of both the IL-12 and the IL-23 receptors and thus, deficiency of IL-12Rβ1 abolishes both IL-12 and IL-23 signaling.

Material And Methods: In this study, we performed whole exon sequencing and confirmatory Sanger sequencing in . Evaluation of the IL12/IFN-γ axis was performed by assessment of patients' whole blood cell to IL12/IFN-γ responding. Total and surface IL-12Rβ1expression was evaluated, in peripheral blood mononuclear cells (PBMCs) and T cell- derived PBMCs, and Th17 count was assessed.

Results: In the present study, we described a c.1791 + 2T > G mutation at a splicing site position in using whole exome sequencing, and confirmed with targeted Sanger sequencing in a 26- year-old patient with Mendelian susceptibility to mycobacterial disease (MSMD) and Crohn's disease (CD). Complete lack of IL-12Rβ1 protein expression was detected in patient's PBMCs, compared to the healthy control. Furthermore, no IL-12Rβ1 protein was expressed on the cell surface. Interestingly, IL-12Rβ1-mutant cells showed an impaired response to IL12, and stimulation, confirming that the mutation is causative in this patient.

Conclusion: A 3'splicing site mutation in , can be corresponding to the abolished expression of in patients' cells, and associated with an impaired IL12-mediated signaling, which may lead not only to MSMD, but also to inflammatory bowel disease (IBD).