Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Long-Term Anti-CD20 Treatment Reduces Antibody-Secreting Ells in NZB/W Lupus Mouse.
Wang2, Wensheng, Owen2, Terasa, Ichikawa2, Travis, Anolik1, Jennifer H.
Although anti-CD20 antibody efficiently depletes most B cells, B-cell depletion (BCD) has shown variable efficacy in clinical trials as a therapy for systemic lupus erythematosus (SLE). To better understand the mechanisms of action of anti-CD20 and the effect on SLE, a lupus-prone mouse model was used to study the alteration in antibody-secreting cells after B cell depletion.
For short-term treatment, NZB/NZWF1 female mice (2430 wks old) with durable proteinuria > 2+ (100 mg/dl) were dosed weekly × 4 with anti-mCD20 antibody (IgG2a, a gift from Biogen Idec)(n=6) or control antibody IgG2a and sacrificed 1 wk after the last treatment. To study longer-term effects of BCD, 27 wk old NZB/NZWF1 female mice with high titer anti-dsDNA antibodies were dosed weekly with anti-mCD20 antibody or control IgG via retro-orbital injection. One group was treated weekly × 4 (n= 6) and sacrificed 8 wks later. Another was treated weekly × 12 (n= 6) and sacrificed 1 wk after the last treatment. Cells from spleen, bone marrow (BM) and kidney were collected and total IgG and dsDNA antibody secreting cells (ASC) were determined by ELIspot.
Nephritis improved after anti-mCD20 treatment (neither 4 wks nor 12 wks treated mice were found to develop nephritis [3+ proteinuria]) compared to control (5/6 mice developed nephritis 4+). Although BCD was efficient (>90% B220+ cell depletion), there was no difference in the numbers of anti-dsDNA-secreting cells and total IgG-secreting cells in either spleen, BM or kidney after 4 treatments of anti-mCD20, over the short-term (evaluation 1 wk after the last treatment- see Table) or long-term (evaluation 8 wks after the last treatment, data not shown). Interestingly, in untreated mice the ratio of anti-dsDNA/total IgG-secreting cells in the kidney was significantly higher than in spleen and BM (p<10-4) suggesting that the kidney is a reservoir of either production or maintenance of autoreactive ASCs. In striking contrast, long-term treatment with anti-mCD20 resulted in significant decreases in total IgG and anti-dsDNA-secreting cells in spleen. In addition, the average size of total IgG-secreting cell spots from kidney decreased significantly, suggesting a shift in the antibody producing capacity after anti-mCD20.
Long-term anti-CD20 treatment significantly reduces ASCs in spleen and moderately reduces ASCs in bone marrow and kidney. Treatment also appears to alter antibody secretion in kidney. Therefore, longer term B cell depletion may have increased efficacy as a treatment for SLE.
|Spleen||115.6 ± 35.6||61.9 ± 17.5||0.12||3.4 ± 1.0||2.6 ± 0.58||0.3|
|BM||15.9 ± 4.2||21.2 ± 3.2||0.26||0.66 ± 0.17||0.46 ± 0.11||0.28|
|Kidney||68.3 ± 4.1||81.5 ± 21.0||0.11||30.3 ± 8.8||37.3 ± 8.3||0.18|
To cite this abstract, please use the following information:
Wang, Wensheng, Owen, Terasa, Ichikawa, Travis, Anolik, Jennifer H.; Long-Term Anti-CD20 Treatment Reduces Antibody-Secreting Ells in NZB/W Lupus Mouse. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :436