IgG <i>N-</i>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 re...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/8/1774 |
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| author | Guillaume Font Marie-Laure Walet-Balieu Marie Petit Carole Burel Maud Maho-Vaillant Vivien Hébert Philippe Chan Manuel Fréret Olivier Boyer Pascal Joly Sébastien Calbo Muriel Bardor Marie-Laure Golinski |
| author_facet | Guillaume Font Marie-Laure Walet-Balieu Marie Petit Carole Burel Maud Maho-Vaillant Vivien Hébert Philippe Chan Manuel Fréret Olivier Boyer Pascal Joly Sébastien Calbo Muriel Bardor Marie-Laure Golinski |
| author_sort | Guillaume Font |
| collection | DOAJ |
| description | 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 <i>N-</i>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 <i>N-</i>glycans. The IgG <i>N-</i>glycome from pemphigus patients and its evolution under rituximab treatment were analyzed. Pemphigus patients presented a different IgG <i>N-</i>glycome than healthy donors, with less galactosylated, sialylated <i>N-</i>glycans, as well as a lower level of <i>N-</i>glycans bearing an additional <i>N-</i>acetylglucosamine. IgG <i>N-</i>glycome from patients who achieved clinical remission was not different to the one observed at baseline. Moreover, our study did not identify the <i>N-</i>glycans profile as discriminating between relapsing and non-relapsing patients. We report that pemphigus patients present a specific IgG <i>N-</i>glycome. The changes observed in these patients could be a biomarker of autoimmunity susceptibility rather than a sign of inflammation. |
| first_indexed | 2024-03-09T04:40:46Z |
| format | Article |
| id | doaj.art-30f11748d2ac4c00a0c8af09a30ebfb4 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T04:40:46Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-30f11748d2ac4c00a0c8af09a30ebfb42023-12-03T13:21:16ZengMDPI AGBiomedicines2227-90592022-07-01108177410.3390/biomedicines10081774IgG <i>N-</i>glycosylation from Patients with Pemphigus Treated with RituximabGuillaume Font0Marie-Laure Walet-Balieu1Marie Petit2Carole Burel3Maud Maho-Vaillant4Vivien Hébert5Philippe Chan6Manuel Fréret7Olivier Boyer8Pascal Joly9Sébastien Calbo10Muriel Bardor11Marie-Laure Golinski12Université de Rouen Normandie, Inserm U1234, CHU Rouen, Department of Dermatology, F-76000 Rouen, FranceUniversité de Rouen Normandie, Laboratoire Glyco-MEV UR 4358, SFR Normandie Végétal FED 4277, Innovation Chimie Carnot, F-76000 Rouen, FranceUniversité de Rouen Normandie, Inserm U1234, F-76000 Rouen, FranceUniversité de Rouen Normandie, Laboratoire Glyco-MEV UR 4358, SFR Normandie Végétal FED 4277, Innovation Chimie Carnot, F-76000 Rouen, FranceUniversité de Rouen Normandie, Inserm U1234, CHU Rouen, Department of Dermatology, F-76000 Rouen, FranceUniversité de Rouen Normandie, Inserm U1234, CHU Rouen, Department of Dermatology, F-76000 Rouen, FranceUniversité de Rouen Normandie, INSERM US 51, CNRS UAR 2026, HeRacLeS-PISSARO, Normandie Université, F-76000 Rouen, FranceUniversité de Rouen Normandie, Inserm U1234, CHU Rouen, Department of Rhumatology, F-76000 Rouen, FranceUniversité de Rouen Normandie, Inserm U1234, CHU Rouen, Department of Immunology and Biotherapy, F-76000 Rouen, FranceUniversité de Rouen Normandie, Inserm U1234, CHU Rouen, Department of Dermatology, F-76000 Rouen, FranceUniversité de Rouen Normandie, Inserm U1234, F-76000 Rouen, FranceUniversité de Rouen Normandie, Laboratoire Glyco-MEV UR 4358, SFR Normandie Végétal FED 4277, Innovation Chimie Carnot, F-76000 Rouen, FranceUniversité de Rouen Normandie, Inserm U1234, CHU Rouen, Department of Dermatology, F-76000 Rouen, FrancePemphigus 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 <i>N-</i>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 <i>N-</i>glycans. The IgG <i>N-</i>glycome from pemphigus patients and its evolution under rituximab treatment were analyzed. Pemphigus patients presented a different IgG <i>N-</i>glycome than healthy donors, with less galactosylated, sialylated <i>N-</i>glycans, as well as a lower level of <i>N-</i>glycans bearing an additional <i>N-</i>acetylglucosamine. IgG <i>N-</i>glycome from patients who achieved clinical remission was not different to the one observed at baseline. Moreover, our study did not identify the <i>N-</i>glycans profile as discriminating between relapsing and non-relapsing patients. We report that pemphigus patients present a specific IgG <i>N-</i>glycome. The changes observed in these patients could be a biomarker of autoimmunity susceptibility rather than a sign of inflammation.https://www.mdpi.com/2227-9059/10/8/1774pemphigusrituximabIgGglycosylation<i>N</i>-glycome<i>N</i>-glycans |
| spellingShingle | Guillaume Font Marie-Laure Walet-Balieu Marie Petit Carole Burel Maud Maho-Vaillant Vivien Hébert Philippe Chan Manuel Fréret Olivier Boyer Pascal Joly Sébastien Calbo Muriel Bardor Marie-Laure Golinski IgG <i>N-</i>glycosylation from Patients with Pemphigus Treated with Rituximab Biomedicines pemphigus rituximab IgG glycosylation <i>N</i>-glycome <i>N</i>-glycans |
| title | IgG <i>N-</i>glycosylation from Patients with Pemphigus Treated with Rituximab |
| title_full | IgG <i>N-</i>glycosylation from Patients with Pemphigus Treated with Rituximab |
| title_fullStr | IgG <i>N-</i>glycosylation from Patients with Pemphigus Treated with Rituximab |
| title_full_unstemmed | IgG <i>N-</i>glycosylation from Patients with Pemphigus Treated with Rituximab |
| title_short | IgG <i>N-</i>glycosylation from Patients with Pemphigus Treated with Rituximab |
| title_sort | igg i n i glycosylation from patients with pemphigus treated with rituximab |
| topic | pemphigus rituximab IgG glycosylation <i>N</i>-glycome <i>N</i>-glycans |
| url | https://www.mdpi.com/2227-9059/10/8/1774 |
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