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  • Dual B cell immunotherapy is superior to individual anti-CD20 depletion or BAFF blockade in murine models of spontaneous or accelerated lupus.

Dual B cell immunotherapy is superior to individual anti-CD20 depletion or BAFF blockade in murine models of spontaneous or accelerated lupus.

Arthritis & rheumatology (Hoboken, N.J.) (2014-10-11)
WeiYu Lin, Dhaya Seshasayee, Wyne P Lee, Patrick Caplazi, Sami McVay, Eric Suto, Allen Nguyen, Zhonghua Lin, Yonglian Sun, Laura DeForge, Mercedesz Balazs, Flavius Martin, Ali A Zarrin
ABSTRACT

To determine whether a combination of B cell depletion and BAFF blockade is more effective than monotherapy in treating models of spontaneous or accelerated systemic lupus erythematosus (SLE) in (NZB × NZW)F1 mice. Clinical parameters such as disease progression-free survival, proteinuria, and renal injury were assessed in models of spontaneous, interferon-α (IFNα)-accelerated, or pristane-accelerated lupus in (NZB × NZW)F1 mice. Treatment arms included anti-CD20 (B cell depletion), B lymphocyte stimulator receptor 3 fusion protein (BR-3-Fc) (BAFF blockade), the combination of anti-CD20 and BR-3-Fc, isotype control, or cyclophosphamide. In models of spontaneous, IFNα-accelerated, or pristane-accelerated lupus, mice were treated for 24 weeks, 8 weeks, or 12 weeks, respectively. Peripheral and resident B cell subsets and various autoantibodies were examined. Compared to B cell depletion or BAFF blockade alone, combined therapy significantly improved disease manifestations in all 3 lupus models. In addition, marginal zone B cells, plasmablasts, and circulating and tissue plasma cells were decreased more effectively. Dual B cell immunotherapy also reduced multiple classes of pathogenic autoantibodies, consistent with its observed effectiveness in reducing immune complex-mediated renal injury. Dual immunotherapy via B cell depletion and BAFF blockade is more efficacious than single agent immunotherapy in murine SLE models, and this combination treatment is predicted to be an effective strategy for immunotherapy in human SLE.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Fluorescein isothiocyanate isomer I, suitable for protein labeling, ≥90% (HPLC), powder
Sigma-Aldrich
Pristane, synthetic, ≥98% (GC)
Sigma-Aldrich
Fluorescein 5(6)-isothiocyanate, BioReagent, suitable for fluorescence, mixture of 2 components, ≥90% (HPLC)
Sigma-Aldrich
Aphidicolin from Nigrospora sphaerica, ≥98% (HPLC), powder
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)
SAFC
Pristane, synthetic, liquid, sterile-filtered, BioReagent
Sigma-Aldrich
Fluorescein 5(6)-isothiocyanate, ≥90% (HPLC)
Cyclophosphamide, European Pharmacopoeia (EP) Reference Standard
Supelco
Aphidicolin, analytical standard
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)