ISERPINB3/I, Adult-Onset Immunodeficiency, and Generalized Pustular Psoriasis

Background: Generalized pustular psoriasis (GPP; MIM 614204) is a rare and severe pustular autoinflammatory skin disease in which acute generalized erythema and scaling develop with numerous sterile pustules. GPP shares skin manifestations, especially pustular skin reaction, with adult-onset immunod...

Full description

Saved in:
Bibliographic Details
Published in:Genes 2023-01, Vol.14 (2)
Main Authors: Kantaputra, Piranit, Daroontum, Teerada, Chuamanochan, Mati, Chaowattanapanit, Suteeraporn, Kiratikanon, Salin, Choonhakarn, Charoen, Intachai, Worrachet, Olsen, Bjorn, Tongsima, Sissades, Ngamphiw, Chumpol, Pontisso, Patrizia, Cox, Timothy C, Ounjai, Puey
Format: Article
Language:English
Subjects:
Demographic aspects
DNA sequencing
Genetic aspects
Immunodeficiency
Methods
Nucleotide sequencing
Physiological aspects
Psoriasis
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background: Generalized pustular psoriasis (GPP; MIM 614204) is a rare and severe pustular autoinflammatory skin disease in which acute generalized erythema and scaling develop with numerous sterile pustules. GPP shares skin manifestations, especially pustular skin reaction, with adult-onset immunodeficiency (AOID) with anti-interferon-γ autoantibodies, an autoimmune disease. Methods: Clinical examinations and whole-exome sequencing (WES) were performed on 32 patients with pustular psoriasis phenotypes and 21 patients with AOID with pustular skin reaction. Immunohistochemical and histopathological studies were performed. Results: WES identified three Thai patients presenting with similar pustular phenotypes—two with a diagnosis of AOID and the other with GPP. A heterozygous missense variant chr18:g.61325778C>A NM_006919.2: c.438G>T; NP_008850.1: p.Lys146Asn; rs193238900 in SERPINB3 was identified in two patients: one with GPP and the other with AOID. The other patient who had AOID carried a heterozygous missense variant chr18:g.61323147T>C NM_006919.2: c.917A>G; NP_008850.1: p.Asp306Gly in SERPINB3. Immunohistochemical studies showed overexpression of SERPINA1 and SERPINB3, a hallmark of psoriatic skin lesions. Conclusions: Genetic variants in SERPINB3 are associated with GPP and AOID with pustular skin reaction. The skin of patients with GPP and AOID carrying SERPINB3 mutations showed overexpression of SERPINB3 and SERPINA1. Clinically and genetically, GPP and AOID appear to share pathogenetic mechanisms.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes14020266