IgG Glycosylation from Patients with Pemphigus Treated with Rituximab.

Pemphigus is a life-threatening auto-immune blistering disease of the skin and mucous membrane that is caused by the production of auto-antibodies (auto-Abs) directed against adhesion proteins: desmoglein 1 and 3. We demonstrated in the "Ritux3" trial, the high efficacy of rituximab, an anti-CD20 recombinant monoclonal antibody, as the first-line treatment for pemphigus. However, 25% of patients relapsed during the six-month period after rituximab treatment. These early relapses were associated with a lower decrease in anti-desmoglein auto-Abs after the initial cycle of rituximab. The glycosylation of immunoglobulin-G (IgG) can affect their affinity for Fc receptors and their serum half-life. We hypothesized that the extended half-life of Abs could be related to modifications of IgG glycans. The IgG glycome from pemphigus patients and its evolution under rituximab treatment were analyzed. Pemphigus patients presented a different IgG glycome than healthy donors, with less galactosylated, sialylated glycans, as well as a lower level of glycans bearing an additional acetylglucosamine. IgG glycome from patients who achieved clinical remission was not different to the one observed at baseline. Moreover, our study did not identify the glycans profile as discriminating between relapsing and non-relapsing patients. We report that pemphigus patients present a specific IgG glycome. The changes observed in these patients could be a biomarker of autoimmunity susceptibility rather than a sign of inflammation.