Ontology type: schema:ScholarlyArticle Open Access: True
2019-12
AUTHORSBerkani Nicolas, Joly Pascal, Golinski Marie-Laure, Colliou Natacha, Lim Annick, Larbi Anis, Riou Gaetan, Caillot Frederique, Bernard Philippe, Bedane Christophe, Delaporte Emmanuel, Chaby Guillaume, Dompmartin Anne, Hertl Michael, Calbo Sebastien, Musette Philippe
ABSTRACTBullous Pemphigoid is the most common auto-immune bullous skin disease. It is characterized by the production of auto-antibodies directed against 2 proteins of the hemi-desmosome (BP180 and BP230). We assessed the efficacy and mechanisms of action of rituximab, an anti-CD20 monoclonal antibody, in 17 patients with severe and relapsing type of bullous pemphigoid. The phenotype, cytokine gene expression, and rearrangement of BP180-specific B-cell receptor genes were performed over 2 years following treatment. At the end of the study, 5 patients had died, 3 had withdrawn from the study, and 9 patients were in complete remission. The one- and two-year relapse rates were 44.1% (95% Confidence Interval (CI): 21.0-76.0%) and 66.5%, (95% CI: 38.4-91.4%), respectively. Phenotypic analyses confirmed dramatic B-cell depletion, which lasted for 9 to 12 months. The ELISA values of serum anti-BP180 antibodies and the frequency of BP180-specific circulating B cells decreased dramatically following treatment, which paralleled the improvement of skin lesions. During B-cell reconstitution, a polyclonal IgM repertoire appeared and a shift in the rearrangement of the B-cell receptor genes of BP180-specific circulating B cells was observed. Concurrently, we observed a decrease of IL-15, IL-6 and TNFα expressing BP180-specific B cells, and the emergence of IL-10 and IL-1RA-expressing BP180-specific IgM+ B cells in patients in complete remission off therapy, suggesting the functional plasticity of BP180-specific auto-immune B cells after rituximab treatment. More... »
PAGES3525
http://scigraph.springernature.com/pub.10.1038/s41598-019-40203-7
DOIhttp://dx.doi.org/10.1038/s41598-019-40203-7
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