SERPINA1, generalized pustular psoriasis, and adult-onset immunodeficiency

J Dermatol. 2021 Oct;48(10):1597-1601. doi: 10.1111/1346-8138.16081. Epub 2021 Aug 12.

Abstract

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.

Keywords: adult-onset immunodeficiency syndrome; anti-interferon-γ autoantibody; generalized pustular psoriasis; hyperactive elastase activity; pustular skin reaction.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Heterozygote
  • Humans
  • Immunologic Deficiency Syndromes*
  • Mutation
  • Psoriasis* / diagnosis
  • Psoriasis* / genetics
  • Skin Diseases, Vesiculobullous*
  • alpha 1-Antitrypsin / genetics*

Substances

  • SERPINA1 protein, human
  • alpha 1-Antitrypsin