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

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.849790

DOI=10.3389/fimmu.2022.849790

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>We studied the distribution and <italic>in vitro</italic> pathogenicity of anti-DSG3 IgG subclasses during the course of pemphigus vulgaris (PV).</p></sec><sec><title>Methods</title><p>We longitudinally studied the distribution of anti-DSG3 IgG subclasses (before <italic>versus</italic> after treatment) in sera from PV patients, using an addressable-laser bead immunoassay (ALBIA). The <italic>in vitro</italic> pathogenicity of corresponding sera was tested using keratinocyte dissociation and immunofluorescence assays.</p></sec><sec><title>Results</title><p>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 <italic>versus</italic> 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 <italic>in vitro</italic> 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.</p></sec><sec><title>Conclusion</title><p>The serum levels and number of anti-DSG3 IgG subclasses drive the pathogenic effect of pemphigus sera and may predict the occurrence of relapses.</p></sec>