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Title:
Mycophenolic acid counteracts B cell proliferation and plasmablast formation in patients with systemic lupus erythematosus | Arthritis Research & Therapy
Description:
Introduction Clinical trials revealed a high efficacy of mycophenolate mofetil (MMF) in inducing and maintaining remission in patients with class III-V-lupus nephritis. Also extrarenal manifestations respond to MMF treatment. However, few attempts have been undertaken to delineate its mechanism of action in systemic lupus erythematosus (SLE) a disease characterized by enhanced B cell activation. Methods Clinical and paraclinical parameters of 107 patients with SLE were recorded consecutively and analyzed retrospectively. Patients were divided into treatment groups (MMF: n = 39, azathioprine (AZA) n = 30 and controls without immunosuppressive therapy n = 38). To further delineate the effect of mycophenolic acid (MPA) on naive and memory B cells in vitro assays were performed. Results Although patients taking AZA flared more frequently than patients on MMF or controls, the analysis of clinical parameters did not reveal significant differences. However, profound differences in paraclinical parameters were found. B cell frequencies and numbers were significantly higher in patients taking MMF compared to those on AZA but lower numbers and frequencies of plasmablasts were detected compared to AZA-treated patients or controls. Notably, MMF treatment was associated with a significantly higher frequency and number of transitional B cells as well as naive B cells compared to AZA treatment. Differences in T cell subsets were not significant. MPA abrogated in vitro proliferation of purified B cells completely but had only moderate impact on B cell survival. Conclusions The thorough inhibition of B cell activation and plasma cell formation by MMF might explain the favorable outcomes of previous clinical trials in patients with SLE, since enhanced B cell proliferation is a hallmark of this disease.
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Keywords {🔍}
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Topics {✒️}
class iii-v-lupus nephritis biotin-labeled anti-igd antibody cd27-igd+cd38+ mature naïve anti-cd40 +il21-induced proliferation cd27+igd+ pre-switched memory cd27+igd- post-switched memory carboxy-fluorescein-succinimidyl ester article download pdf icos-dependent extrafollicular helper mycophenolic acid-mediated suppression purified cd27-igd+ antigen-naïve cell-dependent antibody responses mpa-treated cd3/cd28-activated calculate post-switched memory riedel-de-haen ag full size image anti-cd27-magnetic beads inosine monophosphate dehydrogenase facs canto-ii equipped type-ii-impdh polymorphisms [46] long-lived plasma cells spreptavidin-labeled magnetic beads organ-threatening lupus nephritis systemic lupus erythematosus hla-drlow asc subset hla-drhigh asc counts monoclonal anti-cd40 antibody cd27-igd+cd38++ transitional cd27-igd+cd38+ naïve mycophenolic acid counteracts peripheral hla-drlow asc hladrhigh antibody-secreting cells cd27-igd+ antigen-naïve mycophenolate mofetil impairs fluorochrome-labeled monoclonal antibodies fluorescence-labeled monoclonal antibodies high benefit-risk ratio long-lived lymphocytes il-2-induced stat5 phosphorylation prone mrllpr/lpr mice mycophenolic acid impedes il-21-induced signal transducer serum antibody response long-term belimumab treatment flow cytometric analysis privacy choices/manage cookies differential blood counts full access phospho-flow cytometry central laboratory
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- Boddana P, Webb LH, Unsworth J, Brealey M, Bingham C, Harper SJ: Hypogammaglobulinemia and bronchiectasis in mycophenolate mofetil-treated renal transplant recipients: an emerging clinical phenomenon?
- Borba EF, Saad CG, Pasoto SG, Calich AL, Aikawa NE, Ribeiro AC, Moraes JC, Leon EP, Costa LP, Guedes LK Silva CA, Goncalves CR, Fuller R, Oliveira SA, Ishida MA, Precioso AR, Bonfa E: Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?
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headline:Mycophenolic acid counteracts B cell proliferation and plasmablast formation in patients with systemic lupus erythematosus
description:Clinical trials revealed a high efficacy of mycophenolate mofetil (MMF) in inducing and maintaining remission in patients with class III-V-lupus nephritis. Also extrarenal manifestations respond to MMF treatment. However, few attempts have been undertaken to delineate its mechanism of action in systemic lupus erythematosus (SLE) a disease characterized by enhanced B cell activation. Clinical and paraclinical parameters of 107 patients with SLE were recorded consecutively and analyzed retrospectively. Patients were divided into treatment groups (MMF: n = 39, azathioprine (AZA) n = 30 and controls without immunosuppressive therapy n = 38). To further delineate the effect of mycophenolic acid (MPA) on naive and memory B cells in vitro assays were performed. Although patients taking AZA flared more frequently than patients on MMF or controls, the analysis of clinical parameters did not reveal significant differences. However, profound differences in paraclinical parameters were found. B cell frequencies and numbers were significantly higher in patients taking MMF compared to those on AZA but lower numbers and frequencies of plasmablasts were detected compared to AZA-treated patients or controls. Notably, MMF treatment was associated with a significantly higher frequency and number of transitional B cells as well as naive B cells compared to AZA treatment. Differences in T cell subsets were not significant. MPA abrogated in vitro proliferation of purified B cells completely but had only moderate impact on B cell survival. The thorough inhibition of B cell activation and plasma cell formation by MMF might explain the favorable outcomes of previous clinical trials in patients with SLE, since enhanced B cell proliferation is a hallmark of this disease.
datePublished:2012-05-09T00:00:00Z
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Systemic Lupus Erythematosus
Lupus Nephritis
Cell Subset
Mycophenolic Acid
Lupus Patient
Rheumatology
Orthopedics
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headline:Mycophenolic acid counteracts B cell proliferation and plasmablast formation in patients with systemic lupus erythematosus
description:Clinical trials revealed a high efficacy of mycophenolate mofetil (MMF) in inducing and maintaining remission in patients with class III-V-lupus nephritis. Also extrarenal manifestations respond to MMF treatment. However, few attempts have been undertaken to delineate its mechanism of action in systemic lupus erythematosus (SLE) a disease characterized by enhanced B cell activation. Clinical and paraclinical parameters of 107 patients with SLE were recorded consecutively and analyzed retrospectively. Patients were divided into treatment groups (MMF: n = 39, azathioprine (AZA) n = 30 and controls without immunosuppressive therapy n = 38). To further delineate the effect of mycophenolic acid (MPA) on naive and memory B cells in vitro assays were performed. Although patients taking AZA flared more frequently than patients on MMF or controls, the analysis of clinical parameters did not reveal significant differences. However, profound differences in paraclinical parameters were found. B cell frequencies and numbers were significantly higher in patients taking MMF compared to those on AZA but lower numbers and frequencies of plasmablasts were detected compared to AZA-treated patients or controls. Notably, MMF treatment was associated with a significantly higher frequency and number of transitional B cells as well as naive B cells compared to AZA treatment. Differences in T cell subsets were not significant. MPA abrogated in vitro proliferation of purified B cells completely but had only moderate impact on B cell survival. The thorough inhibition of B cell activation and plasma cell formation by MMF might explain the favorable outcomes of previous clinical trials in patients with SLE, since enhanced B cell proliferation is a hallmark of this disease.
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Systemic Lupus Erythematosus
Lupus Nephritis
Cell Subset
Mycophenolic Acid
Lupus Patient
Rheumatology
Orthopedics
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