Modifications of the BAFF/BAFF-Receptor Axis in Patients With Pemphigus Treated With Rituximab Versus Standard Corticosteroid Regimen
| Autor: | Philippe Musette, Maud Maho-Vaillant, Sébastien Calbo, Gaëtan Riou, Marie-Laure Golinski, Marie Anne Petit, Pascal Joly, Olivier Boyer, Vivien Hébert |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Immunology 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine rituximab immune system diseases Adrenal Cortex Hormones Internal medicine hemic and lymphatic diseases B-Cell Activating Factor medicine Immunology and Allergy Humans Immunologic Factors RNA Messenger B-cell activating factor BAFF receptor B cell Corticosteroïd Original Research 030203 arthritis & rheumatology B-Lymphocytes business.industry RC581-607 medicine.disease BAFF - B-cell activating factor Pemphigus Regimen Endocrinology medicine.anatomical_structure Immunoglobulin class switching BAFF-receptor Corticosteroid Rituximab Immunologic diseases. Allergy business medicine.drug B-Cell Activation Factor Receptor |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| Popis: | The efficacy of the B-cell-depleting agent rituximab has been reported in immune diseases but relapses are frequent, suggesting the need for repeated infusions. The B-cell activating factor (BAFF) is an important factor for B cell survival, class switch recombination and selection of autoreactive B cells, as well as maintaining long-lived plasma cells. It has been hypothesized that relapses after rituximab might be due to the increase of serum BAFF levels. From the Ritux3 trial, we showed that baseline serum BAFF levels were higher in pemphigus patients than in healthy donors (308 ± 13 pg/mL versus 252 ± 28 pg/mL, p=0.037) and in patients with early relapse compared who didn’t (368 ± 92 vs 297 ± 118 pg/mL, p=0.036). Rituximab and high doses of CS alone have different effects on the BAFF/BAFF-R axis. Rituximab led to an increase of BAFF levels associated to a decreased mRNA (Day 0: 12.3 ± 7.6 AU vs Month 36: 3.3 ± 4.3 AU, p=0.01) and mean fluorescence intensity of BAFF-R in non-autoreactive (Day 0: 3232 vs Month 36: 1527, mean difference: 1705, 95%CI: 624 to 2786; p=0.002) as well as on reappearing autoreactive DSG-specific B cells (Day 0: 3873 vs Month 36: 2688, mean difference: 1185, 95%CI: -380 to 2750; p=0.20). Starting high doses of corticosteroids allowed a transitory decrease of serum BAFF levels that re-increased after doses tapering whereas it did not modify BAFF-R expression in autoreactive and non-autoreactive B cells. Our results suggest that the activation of autoreactive B cells at the onset of pemphigus is likely to be related to the presence of high BAFF serum levels and that the decreased BAFF-R expression after rituximab might be responsible for the delayed generation of memory B cells, resulting in a rather long period of mild pemphigus activity after rituximab therapy. Conversely, the incomplete B cell depletion and persistent BAFF-R expression associated with high BAFF serum levels might explain the high number of relapses in patients treated with CS alone. |
| Databáze: | OpenAIRE |
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