Cargando…

Multi-Omics Profiling in PGM3 and STAT3 Deficiencies: A Tale of Two Patients

Hyper-IgE Syndrome (HIES) is a heterogeneous group of primary immune-deficiency disorders characterized by elevated levels of IgE, eczema, and recurrent skin and lung infections. HIES that is autosomally dominant in the signal transducer and activator of transcription 3 (STAT3), and autosomal recess...

Descripción completa

Detalles Bibliográficos
Autores principales: Jacob, Minnie, Masood, Afshan, Abdel Rahman, Anas M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916661/
https://www.ncbi.nlm.nih.gov/pubmed/36768728
http://dx.doi.org/10.3390/ijms24032406
_version_ 1784886180400070656
author Jacob, Minnie
Masood, Afshan
Abdel Rahman, Anas M.
author_facet Jacob, Minnie
Masood, Afshan
Abdel Rahman, Anas M.
author_sort Jacob, Minnie
collection PubMed
description Hyper-IgE Syndrome (HIES) is a heterogeneous group of primary immune-deficiency disorders characterized by elevated levels of IgE, eczema, and recurrent skin and lung infections. HIES that is autosomally dominant in the signal transducer and activator of transcription 3 (STAT3), and autosomal recessive mutations in phosphoglucomutase 3 (PGM3) have been reported in humans. An early diagnosis, based on clinical suspicion and immunological assessments, is challenging. Patients’ metabolomics, proteomics, and cytokine profiles were compared to DOCK 8-deficient and atopic dermatitis patients. The PGM3 metabolomics profile identified significant dysregulation in hypotaurine, hypoxanthine, uridine, and ribothymidine. The eight proteins involved include bifunctional arginine demethylase and lysyl hydroxylase (JMJD1B), type 1 protein phosphatase inhibitor 4 (PPI 4), and platelet factor 4 which aligned with an increased level of the cytokine GCSF. Patients with STAT3 deficiency, on the other hand, showed significant dysregulation in eight metabolites, including an increase in protocatechuic acid, seven proteins including ceruloplasmin, and a plasma protease C1 inhibitor, in addition to cytokine VEGF being dysregulated. Using multi-omics profiling, we identified the dysregulation of endothelial growth factor (EGFR) and tumor necrosis factor (TNF) signaling pathways in PGM3 and STAT3 patients, respectively. Our findings may serve as a stepping stone for larger prospective HIES clinical cohorts to validate their future use as biomarkers.
format Online
Article
Text
id pubmed-9916661
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-99166612023-02-11 Multi-Omics Profiling in PGM3 and STAT3 Deficiencies: A Tale of Two Patients Jacob, Minnie Masood, Afshan Abdel Rahman, Anas M. Int J Mol Sci Case Report Hyper-IgE Syndrome (HIES) is a heterogeneous group of primary immune-deficiency disorders characterized by elevated levels of IgE, eczema, and recurrent skin and lung infections. HIES that is autosomally dominant in the signal transducer and activator of transcription 3 (STAT3), and autosomal recessive mutations in phosphoglucomutase 3 (PGM3) have been reported in humans. An early diagnosis, based on clinical suspicion and immunological assessments, is challenging. Patients’ metabolomics, proteomics, and cytokine profiles were compared to DOCK 8-deficient and atopic dermatitis patients. The PGM3 metabolomics profile identified significant dysregulation in hypotaurine, hypoxanthine, uridine, and ribothymidine. The eight proteins involved include bifunctional arginine demethylase and lysyl hydroxylase (JMJD1B), type 1 protein phosphatase inhibitor 4 (PPI 4), and platelet factor 4 which aligned with an increased level of the cytokine GCSF. Patients with STAT3 deficiency, on the other hand, showed significant dysregulation in eight metabolites, including an increase in protocatechuic acid, seven proteins including ceruloplasmin, and a plasma protease C1 inhibitor, in addition to cytokine VEGF being dysregulated. Using multi-omics profiling, we identified the dysregulation of endothelial growth factor (EGFR) and tumor necrosis factor (TNF) signaling pathways in PGM3 and STAT3 patients, respectively. Our findings may serve as a stepping stone for larger prospective HIES clinical cohorts to validate their future use as biomarkers. MDPI 2023-01-26 /pmc/articles/PMC9916661/ /pubmed/36768728 http://dx.doi.org/10.3390/ijms24032406 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Jacob, Minnie
Masood, Afshan
Abdel Rahman, Anas M.
Multi-Omics Profiling in PGM3 and STAT3 Deficiencies: A Tale of Two Patients
title Multi-Omics Profiling in PGM3 and STAT3 Deficiencies: A Tale of Two Patients
title_full Multi-Omics Profiling in PGM3 and STAT3 Deficiencies: A Tale of Two Patients
title_fullStr Multi-Omics Profiling in PGM3 and STAT3 Deficiencies: A Tale of Two Patients
title_full_unstemmed Multi-Omics Profiling in PGM3 and STAT3 Deficiencies: A Tale of Two Patients
title_short Multi-Omics Profiling in PGM3 and STAT3 Deficiencies: A Tale of Two Patients
title_sort multi-omics profiling in pgm3 and stat3 deficiencies: a tale of two patients
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916661/
https://www.ncbi.nlm.nih.gov/pubmed/36768728
http://dx.doi.org/10.3390/ijms24032406
work_keys_str_mv AT jacobminnie multiomicsprofilinginpgm3andstat3deficienciesataleoftwopatients
AT masoodafshan multiomicsprofilinginpgm3andstat3deficienciesataleoftwopatients
AT abdelrahmananasm multiomicsprofilinginpgm3andstat3deficienciesataleoftwopatients