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.
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.
Authors: Stefanie Sarantopoulos; Kristen E Stevenson; Haesook T Kim; Whitney S Washel; Nazmim S Bhuiya; Corey S Cutler; Edwin P Alyea; Vincent T Ho; Robert J Soiffer; Joseph H Antin; Jerome Ritz Journal: Blood Date: 2010-11-19 Impact factor: 22.113
Authors: Burkhard Möller; Daniel Aeberli; Stefan Eggli; Martin Fuhrer; Istvan Vajtai; Esther Vögelin; Hans-Rudolf Ziswiler; Clemens A Dahinden; Peter M Villiger Journal: Arthritis Res Ther Date: 2009-05-06 Impact factor: 5.156
Authors: Uri Hershberg; Wenzhao Meng; Bochao Zhang; Nancy Haff; E William St Clair; Philip L Cohen; Patrice D McNair; Ling Li; Marc C Levesque; Eline T Luning Prak Journal: Arthritis Res Ther Date: 2014-02-11 Impact factor: 5.156