Modulation of molecular imprints in the antigen-experienced B cell repertoire by rituximab.
Arthritis Rheum
; 58(12): 3665-74, 2008 Dec.
Article
em En
| MEDLINE
| ID: mdl-19035487
ABSTRACT
OBJECTIVE:
Transient B cell depletion by rituximab has recently gained more importance in the treatment of rheumatic disorders. Nevertheless, little is known about the reemerging B cells. We analyzed dynamic changes in the repopulating B cells, particularly the postswitch B cells, and studied the mutational patterns of Ig genes in antigen-experienced B cells.METHODS:
Five patients with active rheumatoid arthritis (RA) were treated with rituximab. In 3 patients, B cell receptor (BCR) gene analysis was performed before treatment and during B cell recovery using genomic DNA. In 2 patients, B cell subsets were studied during the early recovery phase using single-cell technology. For comparison, immunophenotyping of B cell subsets was performed.RESULTS:
Early B cell recovery was marked by a relatively expanded population of highly mutated B cells, which were correlated with B cells with a plasmablast phenotype on comparative immunophenotyping. Analysis of the mutational pattern in these cells revealed increased RGYW/WRCY (where R = A/G, Y = C/T, and W = A/T) hotspot targeting (44% before rituximab versus 59% after) and elevated ratios of replacement to silent mutations within the complementarity-determining regions in Ig genes (1.87 before rituximab versus 2.67 after; P < or = 0.0025).CONCLUSION:
Our findings show that rituximab leads to qualitative changes in the imprints of highly mutated, antigen-experienced BCRs, representing the result of selection, whereas molecular processes such as Ig V rearrangements are not affected by this treatment.
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Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Linfócitos B
/
Antirreumáticos
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Anticorpos Monoclonais
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article