Therapeutic B cell depletion and regeneration in rheumatoid arthritis: Emerging patterns and paradigms

2006 ◽  
Vol 54 (8) ◽  
pp. 2356-2367 ◽  
Author(s):  
Gregg J. Silverman
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Emerging Patterns

scholarly journals Induction of long-term B-cell depletion in refractory rheumatoid arthritis patients preferentially affects autoreactive more than protective humoral immunity

2012 ◽  
Vol 14 (2) ◽  
pp. R57 ◽  
Author(s):  
YK Onno Teng ◽  
Gillian Wheater ◽  
Vanessa E Hogan ◽  
Philip Stocks ◽  
EW Nivine Levarht ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Humoral Immunity ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Refractory Rheumatoid Arthritis

scholarly journals IFN signature determines responder status on B cell depletion in rheumatoid arthritis patients

2010 ◽  
Vol 69 (Suppl 2) ◽  
pp. A12-A12
Author(s):  
S Vosslamber ◽  
H G Raterman ◽  
M Schreurs ◽  
T van der Pouw Kraan ◽  
M T Nurmohamed ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion

Steady-state generation of mucosal IgA+ plasmablasts is not abrogated by B-cell depletion therapy with rituximab

Blood ◽  
2010 ◽  
Vol 116 (24) ◽  
pp. 5181-5190 ◽  
Author(s):  
Henrik E. Mei ◽  
Daniela Frölich ◽  
Claudia Giesecke ◽  
Christoph Loddenkemper ◽  
Karin Reiter ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Steady State ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Ki 67

AbstractThe anti-CD20 antibody rituximab depletes human B cells from peripheral blood, but it remains controversial to what extent tissue-resident B cells are affected. In representative patients with rheumatoid arthritis, we here demonstrate that recently activated presumably short-lived plasmablasts expressing HLA-DRhigh and Ki-67 continuously circulate in peripheral blood after B-cell depletion by rituximab at 26%-119% of their initial numbers. They circulate independent of splenectomy, express immunoglobulin A (IgA), β7 integrin, and C-C motif receptor 10 (CCR10) and migrate along CCL28 gradients in vitro, suggesting their mucosal origin. These plasmablasts express somatically hypermutated VH gene rearrangements and spontaneously secrete IgA, exhibiting binding to microbial antigens. Notably, IgA+ plasmablasts and plasma cells were identified in the lamina propria of patients treated with rituximab during peripheral B-cell depletion. Although a relation of these “steady state”–like plasmablasts with rheumatoid arthritis activity could not be found, their persistence during B-cell depletion indicates that their precursors, that is, B cells resident in the mucosa are not deleted by this treatment. These data suggest that a population of mucosal B cells is self-sufficient in adult humans and not replenished by CD20+ B cells immigrating from blood, lymphoid tissue, or bone marrow, that is, B cells depleted by rituximab.

scholarly journals A5.8 B Cell Depletion Therapy in a Cohort of Patients with Seropositive and Seronegative Rheumatoid Arthritis: Abstract A5.8 Table 1

2013 ◽  
Vol 72 (Suppl 1) ◽  
pp. A32.3-A33
Author(s):  
ML Velloso Feijoo ◽  
R Martínez Pérez ◽  
L Mayordomo Gonzalez ◽  
JL Marenco de la Fuente
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion

B-cell-activating factor receptor expression on naive and memory B cells: relationship with relapse in patients with rheumatoid arthritis following B-cell depletion therapy

2010 ◽  
Vol 69 (12) ◽  
pp. 2181-2188 ◽  
Author(s):  
Inmaculada de la Torre ◽  
Rita A Moura ◽  
Maria J Leandro ◽  
Jonathan Edwards ◽  
Geraldine Cambridge
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Receptor Expression ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
B Cell Activating Factor ◽  
Significant Difference ◽  
Cell Repopulation

ObjectivesTo examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27− and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab.Patients and MethodsBAFF-R expression on B-cell subsets was determined in normal controls (NC; n=11), active patients with RA pre-rituximab (pre-RX; n=15), relapsing patients either concordant for B-cell repopulation (C-R, n=13) or discordant, with relapse more than 3 months after repopulation (D-R, n=11) and patients in remission over 3 months postrepopulation (discordant non-relapsing (D-NR), n=5). Serum BAFF was measured by ELISA and analysed using Mann–Whitney.ResultsThere was no significant difference between NC, pre-RX and D-NR patients in %BAFF-R-positive B cells or mean fluorescence intensity (MFI) in naive and memory B cells. Relapsing patients had significantly lower MFI and %BAFF-R-positive cells in both naive and memory compartments from NC and pre-RX (C-R and D-R; p<0.01). BAFF levels in pre-RX patients were within the normal range and did not correlate with BAFF-R expression in any patient group. D-NR patients had relatively lower proportions of pre and postswitch CD27+ B cells than pre-RX patients (D-NR vs pre-RX; p<0.05 for both) and also lower numbers of postswitch B cells than D-R patients (D-NR vs D-R, p<0.05).ConclusionBAFF-R expression was significantly reduced on both naive and memory B cells in patients at relapse, regardless of the relationship with B-cell repopulation or serum BAFF levels. Re-establishment of active disease was also associated with an increase in class-switch recombination. Factors responsible for lower levels of BAFF-R may relate to altered thresholds for autoreactive B-cell generation at relapse in patients with RA.

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