SERPINA1, generalized pustular psoriasis, and adult-onset immunodeficiency.
adult-onset immunodeficiency syndrome
anti-interferon-γ autoantibody
generalized pustular psoriasis
hyperactive elastase activity
pustular skin reaction
Journal
The Journal of dermatology
ISSN: 1346-8138
Titre abrégé: J Dermatol
Pays: England
ID NLM: 7600545
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
11
05
2021
accepted:
11
07
2021
pubmed:
15
8
2021
medline:
6
10
2021
entrez:
14
8
2021
Statut:
ppublish
Résumé
Adult-onset immunodeficiency syndrome (AOID) with anti-interferon (IFN)-γ autoantibodies is characterized by an AIDS-like illness with disruptive IFN-γ signaling. Patients generally present with recurrent and disseminated opportunistic infections along with neutrophilic dermatoses. Generalized pustular psoriasis (GPP; Online Mendelian Inheritance in Man #614204) is characterized by acute generalized erythema and scaling with numerous aseptic pustules. Mutations in SERPINA3 have been reported as predisposing risk factors for both AOID and GPP. Here, we report two unrelated patients, one with AOID and a pustular skin reaction and the other with GPP, who both carried the same heterozygous variant c.718G>A (p.Val240Met) in SERPINA1. Our observation of a shared mutation in SERPINA1 in AOID and GPP indicate possible pathobiological and disease mechanism similarities in these two disorders. Thus, variants in both SERPINA1, SERPINA3, and potentially other SERPIN family members may be associated with the etiology of GPP and AOID.
Identifiants
pubmed: 34390020
doi: 10.1111/1346-8138.16081
doi:
Substances chimiques
SERPINA1 protein, human
0
alpha 1-Antitrypsin
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1597-1601Subventions
Organisme : Thailand Research Fund
ID : BRG6180007
Organisme : Health Systems Research Institute
ID : 63-118
Organisme : Thailand Research Fund and the Genomics Thailand Research Grant of Health Systems Research Institute (HSRI)
Organisme : Chiang Mai University Faculty of Medicine Research Fund
ID : 120/2563
Informations de copyright
© 2021 Japanese Dermatological Association.
Références
Ku CL, Chi CY, von Bernuth H, Doffinger R. Autoantibodies against cytokines: phenocopies of primary immunodeficiencies? Hum Genet. 2020;139:783-94.
Jutivorakool K, Sittiwattanawong P, Kantikosum K, Hurst C, Kumtornrut C, Asawanonda P, et al. Skin manifestations in patients with adult-onset immunodeficiency due to anti-interferon-gamma autoantibody: a relationship with systemic infections. Acta Derm Venereol. 2018;98:742-7.
Frey S, Sticht H, Wilsmann-Theis D, Gerschütz A, Wolf K, Löhr S, et al. Rare loss-of-function mutation in SERPINA3 in generalized pustular psoriasis. J Invest Dermatol. 2020;140:1451-1455.e13.
Uppala R, Tsoi LC, Harms PW, Wang B, Billi AC, Maverakis E, et al. "Autoinflammatory psoriasis" genetics and biology of pustular psoriasis. Cell Mol Immunol. 2021;18:307-17.
Kantaputra PN, Chuamanochan M, Kiratikano S, Chiewchanvit S, Chaiwarith R, Intachai W, et al. A truncating variant in SERPINA3, skin pustules and adult-onset immunodeficiency. J Dermatol. https://doi.org/10.1111/1346-8138.15942
Johnston A, Xing X, Wolterink L, Barnes DH, Yin Z, Reingold L, et al. IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis. J Allergy Clin Immunol. 2017;140:109-20.
Patschull AO, Segu L, Nyon MP, Lomas DA, Nobeli I, Barrett TE, et al. Therapeutic target-site variability in α1-antitrypsin characterized at high resolution. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011;67:1492-7.
Yamasaki M, Sendall TJ, Pearce MC, Whisstock JC, Huntington JA. Molecular basis of α1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer. EMBO Rep. 2011;12:1011-7.
Song S. Alpha-1 antitrypsin therapy for autoimmune disorders. Chronic Obstr Pulm Dis. 2018;5:289-301.
Pelissier P, Delourme D, Germot A, Blanchet X, Becila S, Maftah A, et al. An original SERPINA3 gene cluster: elucidation of genomic organization and gene expression in the Bos taurus 21q24 region. BMC Genom. 2008;9:151.
Bergin DA, Reeves EP, Hurley K, Wolfe R, Jameel R, Fitzgerald S, et al. The circulating proteinase inhibitor α-1 antitrypsin regulates neutrophil degranulation and autoimmunity. Sci Transl Med. 2014;6:217ra1.
Akiyama M, Takeichi T, McGrath JA, Sugiura K. Autoinflammatory keratinization diseases: an emerging concept encompassing various inflammatory keratinization disorders of the skin. J Dermatol Sci. 2018;90:105-11.
McCarthy C, Reeves EP, McElvaney NG. The role of neutrophils in alpha-1-antitrypsin deficiency. Ann Am Thorac Soc. 2016;13(Suppl 4):S297-304.
Meffre E, O'Connor KC. Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies. Immunol Rev. 2019;292:90-101.
Elshikha AS, Lu Y, Chen MJ, Akbar M, Zeumer L, Ritter A, et al. Alpha 1 antitrypsin inhibits dendritic cell activation and attenuates nephritis in a mouse model of lupus. PLoS One. 2016;11:e0156583.