Cargando…
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 di...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879969/ https://www.ncbi.nlm.nih.gov/pubmed/31788565 http://dx.doi.org/10.1016/j.jctube.2019.100123 |
_version_ | 1783473674246946816 |
---|---|
author | Khoshnevisan, Razieh Nekooei-marnany, Nioosha Klein, Christoph Kotlarz, Daniel Behnam, Mahdieh Ostadi, Vajihe Yaran, Majid Rezaei, Abbas Sherkat, Roya |
author_facet | Khoshnevisan, Razieh Nekooei-marnany, Nioosha Klein, Christoph Kotlarz, Daniel Behnam, Mahdieh Ostadi, Vajihe Yaran, Majid Rezaei, Abbas Sherkat, Roya |
author_sort | Khoshnevisan, Razieh |
collection | PubMed |
description | 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 IL-12Rβ1. 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 IL-12Rβ1, 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 Bacillus Calmette–Guérin stimulation, confirming that the mutation is causative in this patient. CONCLUSION: A 3′splicing site mutation in IL12Rβ1, can be corresponding to the abolished expression of IL12Rβ1 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). |
format | Online Article Text |
id | pubmed-6879969 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-68799692019-11-29 IL-12Rβ1 deficiency corresponding to concurrency of two diseases, mendelian susceptibility to mycobacterial disease and Crohn's disease Khoshnevisan, Razieh Nekooei-marnany, Nioosha Klein, Christoph Kotlarz, Daniel Behnam, Mahdieh Ostadi, Vajihe Yaran, Majid Rezaei, Abbas Sherkat, Roya J Clin Tuberc Other Mycobact Dis Article 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 IL-12Rβ1. 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 IL-12Rβ1, 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 Bacillus Calmette–Guérin stimulation, confirming that the mutation is causative in this patient. CONCLUSION: A 3′splicing site mutation in IL12Rβ1, can be corresponding to the abolished expression of IL12Rβ1 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). Elsevier 2019-09-20 /pmc/articles/PMC6879969/ /pubmed/31788565 http://dx.doi.org/10.1016/j.jctube.2019.100123 Text en © 2019 Published by Elsevier Ltd. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Khoshnevisan, Razieh Nekooei-marnany, Nioosha Klein, Christoph Kotlarz, Daniel Behnam, Mahdieh Ostadi, Vajihe Yaran, Majid Rezaei, Abbas Sherkat, Roya IL-12Rβ1 deficiency corresponding to concurrency of two diseases, mendelian susceptibility to mycobacterial disease and Crohn's disease |
title | IL-12Rβ1 deficiency corresponding to concurrency of two diseases, mendelian susceptibility to mycobacterial disease and Crohn's disease |
title_full | IL-12Rβ1 deficiency corresponding to concurrency of two diseases, mendelian susceptibility to mycobacterial disease and Crohn's disease |
title_fullStr | IL-12Rβ1 deficiency corresponding to concurrency of two diseases, mendelian susceptibility to mycobacterial disease and Crohn's disease |
title_full_unstemmed | IL-12Rβ1 deficiency corresponding to concurrency of two diseases, mendelian susceptibility to mycobacterial disease and Crohn's disease |
title_short | IL-12Rβ1 deficiency corresponding to concurrency of two diseases, mendelian susceptibility to mycobacterial disease and Crohn's disease |
title_sort | il-12rβ1 deficiency corresponding to concurrency of two diseases, mendelian susceptibility to mycobacterial disease and crohn's disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879969/ https://www.ncbi.nlm.nih.gov/pubmed/31788565 http://dx.doi.org/10.1016/j.jctube.2019.100123 |
work_keys_str_mv | AT khoshnevisanrazieh il12rb1deficiencycorrespondingtoconcurrencyoftwodiseasesmendeliansusceptibilitytomycobacterialdiseaseandcrohnsdisease AT nekooeimarnanynioosha il12rb1deficiencycorrespondingtoconcurrencyoftwodiseasesmendeliansusceptibilitytomycobacterialdiseaseandcrohnsdisease AT kleinchristoph il12rb1deficiencycorrespondingtoconcurrencyoftwodiseasesmendeliansusceptibilitytomycobacterialdiseaseandcrohnsdisease AT kotlarzdaniel il12rb1deficiencycorrespondingtoconcurrencyoftwodiseasesmendeliansusceptibilitytomycobacterialdiseaseandcrohnsdisease AT behnammahdieh il12rb1deficiencycorrespondingtoconcurrencyoftwodiseasesmendeliansusceptibilitytomycobacterialdiseaseandcrohnsdisease AT ostadivajihe il12rb1deficiencycorrespondingtoconcurrencyoftwodiseasesmendeliansusceptibilitytomycobacterialdiseaseandcrohnsdisease AT yaranmajid il12rb1deficiencycorrespondingtoconcurrencyoftwodiseasesmendeliansusceptibilitytomycobacterialdiseaseandcrohnsdisease AT rezaeiabbas il12rb1deficiencycorrespondingtoconcurrencyoftwodiseasesmendeliansusceptibilitytomycobacterialdiseaseandcrohnsdisease AT sherkatroya il12rb1deficiencycorrespondingtoconcurrencyoftwodiseasesmendeliansusceptibilitytomycobacterialdiseaseandcrohnsdisease |