The Diversity of Serum Anti-DSG3 IgG Subclasses Has a Major Impact on Pemphigus Activity and Is Predictive of Relapses After Treatment With Rituximab

Copyright © 2022 Golinski, Lemieux, Maho-Vaillant, Barray, Drouot, Schapman, Petit, Hertl, Boyer, Calbo, Joly and Hébert..

Introduction: We studied the distribution and in vitro pathogenicity of anti-DSG3 IgG subclasses during the course of pemphigus vulgaris (PV).

Methods: We longitudinally studied the distribution of anti-DSG3 IgG subclasses (before versus after treatment) in sera from PV patients, using an addressable-laser bead immunoassay (ALBIA). The in vitro pathogenicity of corresponding sera was tested using keratinocyte dissociation and immunofluorescence assays.

Results: Sixty-five sera were assessed at baseline (33 from patients treated with rituximab and 32 with corticosteroids). Sixty-three percent of these baseline sera contained 2 or more anti-DSG3 IgG subclasses versus 35.7% of sera from patients in complete remission (CR) and 75.0% of sera from patients with persistent disease activity after treatment. IgG4 was the most frequently detected anti-DSG3 IgG subclass, both in patients with disease activity and in those in CR. The presence of three or more anti-DSG3 IgG subclasses was predictive of relapse, in particular when it included IgG3, with a positive predictive value of 62.5% and a negative predictive value of 92%. While anti-DSG3 IgG4 Abs from sera collected before treatment were most often pathogenic, anti-DSG3 IgG4 from sera collected after treatment were pathogenic only after adjusting their titer to the one measured before treatment. The IgG3 fraction containing anti-DSG3 Abs also had an in vitro pathogenic effect. The disappearance of the pathogenic effect of some sera after removal of anti-DSG3 IgG3 suggested an additional effect of this IgG subclass.

Conclusion: The serum levels and number of anti-DSG3 IgG subclasses drive the pathogenic effect of pemphigus sera and may predict the occurrence of relapses.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Frontiers in immunology - 13(2022) vom: 20., Seite 849790

Sprache:

Englisch

Beteiligte Personen:

Golinski, Marie-Laure [VerfasserIn]
Lemieux, Alexandre [VerfasserIn]
Maho-Vaillant, Maud [VerfasserIn]
Barray, Marion [VerfasserIn]
Drouot, Laurent [VerfasserIn]
Schapman, Damien [VerfasserIn]
Petit, Marie [VerfasserIn]
Hertl, Michael [VerfasserIn]
Boyer, Olivier [VerfasserIn]
Calbo, Sébastien [VerfasserIn]
Joly, Pascal [VerfasserIn]
Hébert, Vivien [VerfasserIn]

Links:

Volltext

Themen:

4F4X42SYQ6
Autoantibodies
Desmoglein 3
Immunoglobulin G
Immunoglobulin subclasses
Journal Article
Pathogenicity
Pemphigus
Research Support, Non-U.S. Gov't
Rituximab

Anmerkungen:

Date Completed 08.04.2022

Date Revised 03.07.2022

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.3389/fimmu.2022.849790

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM339009578