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Loss of Function TGFBR2 Variant as a Contributing Factor in Generalized Pustular Psoriasis and Adult-Onset Immunodeficiency
Background: Generalized pustular psoriasis (GPP; MIM 614204) is a rare multisystemic autoinflammatory disease, characterized by episodes of acute generalized erythema and scaling developed with the spread of numerous sterile pustules. Adult-onset immunodeficiency syndrome (AOID) with anti-interferon...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859322/ https://www.ncbi.nlm.nih.gov/pubmed/36672844 http://dx.doi.org/10.3390/genes14010103 |
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author | Kantaputra, Piranit Daroontum, Teerada Chuamanochan, Mati Chaowattanapanit, Suteeraporn Intachai, Worrachet Olsen, Bjorn Sastraruji, Thanapat Tongsima, Sissades Ngamphiw, Chumpol Kampuansai, Jatupol Cox, Timothy C. Kiratikanon, Salin |
author_facet | Kantaputra, Piranit Daroontum, Teerada Chuamanochan, Mati Chaowattanapanit, Suteeraporn Intachai, Worrachet Olsen, Bjorn Sastraruji, Thanapat Tongsima, Sissades Ngamphiw, Chumpol Kampuansai, Jatupol Cox, Timothy C. Kiratikanon, Salin |
author_sort | Kantaputra, Piranit |
collection | PubMed |
description | Background: Generalized pustular psoriasis (GPP; MIM 614204) is a rare multisystemic autoinflammatory disease, characterized by episodes of acute generalized erythema and scaling developed with the spread of numerous sterile pustules. Adult-onset immunodeficiency syndrome (AOID) with anti-interferon-γ autoantibodies is an immunodeficiency disorder associated with disruptive IFN-γ signaling. Methods: Clinical examination and whole exome sequencing (WES) were performed on 32 patients with pustular psoriasis phenotypes and 21 patients with AOID with pustular skin reaction. Histopathological and immunohistochemical studies were performed. Results: WES identified four Thai patients presenting with similar pustular phenotypes—two with a diagnosis of GPP and the other two with AOID—who were found to carry the same rare TGFBR2 frameshift mutation c.458del; p.Lys153SerfsTer35, which is predicted to result in a marked loss of functional TGFBR2 protein. The immunohistochemical studied showed overexpression of IL1B, IL6, IL17, IL23, IFNG, and KRT17, a hallmark of psoriatic skin lesions. Abnormal TGFB1 expression was observed in the pustular skin lesion of an AOID patient, suggesting disruption to TGFβ signaling is associated with the hyperproliferation of the psoriatic epidermis. Conclusions: This study implicates disruptive TGFBR2-mediated signaling, via a shared truncating variant, c.458del; p.Lys153SerfsTer35, as a “predisposing risk factor” for GPP and AOID. |
format | Online Article Text |
id | pubmed-9859322 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98593222023-01-21 Loss of Function TGFBR2 Variant as a Contributing Factor in Generalized Pustular Psoriasis and Adult-Onset Immunodeficiency Kantaputra, Piranit Daroontum, Teerada Chuamanochan, Mati Chaowattanapanit, Suteeraporn Intachai, Worrachet Olsen, Bjorn Sastraruji, Thanapat Tongsima, Sissades Ngamphiw, Chumpol Kampuansai, Jatupol Cox, Timothy C. Kiratikanon, Salin Genes (Basel) Article Background: Generalized pustular psoriasis (GPP; MIM 614204) is a rare multisystemic autoinflammatory disease, characterized by episodes of acute generalized erythema and scaling developed with the spread of numerous sterile pustules. Adult-onset immunodeficiency syndrome (AOID) with anti-interferon-γ autoantibodies is an immunodeficiency disorder associated with disruptive IFN-γ signaling. Methods: Clinical examination and whole exome sequencing (WES) were performed on 32 patients with pustular psoriasis phenotypes and 21 patients with AOID with pustular skin reaction. Histopathological and immunohistochemical studies were performed. Results: WES identified four Thai patients presenting with similar pustular phenotypes—two with a diagnosis of GPP and the other two with AOID—who were found to carry the same rare TGFBR2 frameshift mutation c.458del; p.Lys153SerfsTer35, which is predicted to result in a marked loss of functional TGFBR2 protein. The immunohistochemical studied showed overexpression of IL1B, IL6, IL17, IL23, IFNG, and KRT17, a hallmark of psoriatic skin lesions. Abnormal TGFB1 expression was observed in the pustular skin lesion of an AOID patient, suggesting disruption to TGFβ signaling is associated with the hyperproliferation of the psoriatic epidermis. Conclusions: This study implicates disruptive TGFBR2-mediated signaling, via a shared truncating variant, c.458del; p.Lys153SerfsTer35, as a “predisposing risk factor” for GPP and AOID. MDPI 2022-12-29 /pmc/articles/PMC9859322/ /pubmed/36672844 http://dx.doi.org/10.3390/genes14010103 Text en © 2022 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 | Article Kantaputra, Piranit Daroontum, Teerada Chuamanochan, Mati Chaowattanapanit, Suteeraporn Intachai, Worrachet Olsen, Bjorn Sastraruji, Thanapat Tongsima, Sissades Ngamphiw, Chumpol Kampuansai, Jatupol Cox, Timothy C. Kiratikanon, Salin Loss of Function TGFBR2 Variant as a Contributing Factor in Generalized Pustular Psoriasis and Adult-Onset Immunodeficiency |
title | Loss of Function TGFBR2 Variant as a Contributing Factor in Generalized Pustular Psoriasis and Adult-Onset Immunodeficiency |
title_full | Loss of Function TGFBR2 Variant as a Contributing Factor in Generalized Pustular Psoriasis and Adult-Onset Immunodeficiency |
title_fullStr | Loss of Function TGFBR2 Variant as a Contributing Factor in Generalized Pustular Psoriasis and Adult-Onset Immunodeficiency |
title_full_unstemmed | Loss of Function TGFBR2 Variant as a Contributing Factor in Generalized Pustular Psoriasis and Adult-Onset Immunodeficiency |
title_short | Loss of Function TGFBR2 Variant as a Contributing Factor in Generalized Pustular Psoriasis and Adult-Onset Immunodeficiency |
title_sort | loss of function tgfbr2 variant as a contributing factor in generalized pustular psoriasis and adult-onset immunodeficiency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859322/ https://www.ncbi.nlm.nih.gov/pubmed/36672844 http://dx.doi.org/10.3390/genes14010103 |
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