Separate Gut Plasma Cell Populations Produce Auto-Antibodies against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis

Saykat Das, Jorunn Stamnaes, Esko Kemppainen, Kaisa Hervonen, Knut E.A. Lundin, Naveen Parmar, Frode L. Jahnsen, Jørgen Jahnsen, Katri Lindfors, Teea Salmi, Rasmus Iversen, Ludvig M. Sollid

    Research output: Contribution to journalArticleScientificpeer-review

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    Abstract

    Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto-antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto-antibodies reactive with both transglutaminase enzymes. Here it is reported that in DH both gut plasma cells and serum auto-antibodies are specific for either TG2 or TG3 with no TG2–TG3 cross reactivity. By generating monoclonal antibodies from TG3-specific duodenal plasma cells of DH patients, three conformational epitope groups are defined. Both TG2-specific and TG3-specific gut plasma cells have few immunoglobulin (Ig) mutations, and the two transglutaminase-reactive populations show distinct selection of certain heavy and light chain V-genes. Mass spectrometry analysis of TG3-specific serum IgA corroborates preferential usage of IGHV2-5 in combination with IGKV4-1. Collectively, these results demonstrate parallel induction of anti-TG2 and anti-TG3 auto-antibody responses involving separate B-cell populations in DH patients.

    Original languageEnglish
    Article number2300401
    JournalAdvanced science
    Volume10
    Issue number25
    DOIs
    Publication statusPublished - 2023
    Publication typeA1 Journal article-refereed

    Keywords

    • auto-antibodies
    • celiac disease
    • cross reactivity
    • dermatitis herpetiformis
    • transglutaminase 2
    • transglutaminase 3

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • General Chemical Engineering
    • General Materials Science
    • Biochemistry, Genetics and Molecular Biology (miscellaneous)
    • General Engineering
    • General Physics and Astronomy

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