TY - JOUR
TI - Clonal expansion of B-cells in human systemic lupus erythematosus:
Evidence from studies before and after therapeutic B-cell depletion
AU - Sfikakis, Petros P.
AU - Karali, Vassiliki
AU - Lilakos, Konstantinos and
AU - Georgiou, George
AU - Panayiotidis, Panayiotis
JO - Clinical Immunology Newsletter
PY - 2009
VL - 132
TODO - 1
SP - 19-31
PB - ACADEMIC PRESS INC ELSEVIER SCIENCE
SN - 0197-1859
TODO - 10.1016/j.clim.2009.02.010
TODO - SLE; B-cell; Immunoglobulin heavy-chain repertoire; Rituximab; Nephritis
TODO - Anti-B-cell therapy may be beneficial for patients with SLE and active
proliferative glomerulonephritis. Using genomic DNA, we examined how
rituximab-induced transient B-cell depletion affected the composition of
immunoglobulin heavy-chain (IG-V-H/D-H/J(H)) repertoire at the
time-point of 33-35% B-cell reconstitution in these patients. Clusters
of clonaly-related Ig-V-H/D-H/J(H) sequences were evident in all 7
patients with active SLE but in none of 4 healthy subjects studied for
comparison. In addition to original somatic mutation(s) shared in the
majority of clonaly-related sequences, ongoing mutation suggested
expansion of single B-cell precursors and clonal evolution. Otherwise,
lupus repertoire was similar to that of healthy subjects with the
exception of increased somatic hypermutation. The regenerating
repertoire was diverse and comparable to baseline, albeit with fewer
somatic mutations but more clonal expansions. Since clonal expansion may
lead to preferential survival/growth of potentially autoreactive B-cells
further studies are warranted, especially as therapies aiming to reduce
B-cell survival emerge. (C) 2009 Elsevier Inc. All rights reserved.
ER -