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Article

Susceptibility of alpha-1 antitrypsin deficiency variants to polymer-blocking therapy.

JCI insight - 8 Aug 2025

Ronzoni Riccardo, Aldobiyan Ibrahim, Miranda Elena, Heyer-Chauhan Narinder, Elliston Emma Lk, Pérez Juan, Fra Annamaria, Irving James A, Lomas David A

Abstract excerpt

The Z variant (Glu342Lys) causes alpha-1 antitrypsin (AAT) to self-assemble into polymer chains that accumulate within hepatocytes, causing liver disease and exposing a cryptic epitope recognized by the 2C1 monoclonal antibody (mAb). They can be blocked by the small molecule GSK716 ('716) that stabilizes an intermediate on the polymerization pathway. We have characterized 23 mutants of AAT in a cellular model to...

Read the complete abstract on PubMed

Topics

alpha 1-Antitrypsin Deficiency
alpha 1-Antitrypsin
Humans
Antibodies, Monoclonal
Polymers
Mutation

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Hepatocytes

Epitopes

Polymerization

Source

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Identifiers

PMID: 40627447
DOI: 10.1172/jci.insight.194354
PMCID: PMC12333946

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 25 Oct 2026.

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