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Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study

We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an open clinical trial, 22 patients with active systemic lupus erythematosis and renal involvement (mainly class III and IV according to the WHO classification) that was refractory...

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Autores principales: Vigna-Perez, Mónica, Hernández-Castro, Berenice, Paredes-Saharopulos, Octavio, Portales-Pérez, Diana, Baranda, Lourdes, Abud-Mendoza, Carlos, González-Amaro, Roberto
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526618/
https://www.ncbi.nlm.nih.gov/pubmed/16677395
http://dx.doi.org/10.1186/ar1954
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author Vigna-Perez, Mónica
Hernández-Castro, Berenice
Paredes-Saharopulos, Octavio
Portales-Pérez, Diana
Baranda, Lourdes
Abud-Mendoza, Carlos
González-Amaro, Roberto
author_facet Vigna-Perez, Mónica
Hernández-Castro, Berenice
Paredes-Saharopulos, Octavio
Portales-Pérez, Diana
Baranda, Lourdes
Abud-Mendoza, Carlos
González-Amaro, Roberto
author_sort Vigna-Perez, Mónica
collection PubMed
description We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an open clinical trial, 22 patients with active systemic lupus erythematosis and renal involvement (mainly class III and IV according to the WHO classification) that was refractory to conventional therapy were studied. In all these patients, Rituximab (0.5 to 1.0 g at days 1 and 15) was added to the immunosuppressive therapy and its therapeutic effect was evaluated. In addition, the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed. We found a significant reduction in disease activity (p < 0.05, MEX-SLEDAI index), and proteinuria (p < 0.05) at days 60 and 90 of Rituximab therapy. Although most patients showed improvement in creatinine clearance and erythrocyturia, no significant changes in these parameters were detected. In most patients (20/22), B cell depletion was observed, but no clear-cut effect of Rituximab on complement levels or auto-antibody titers was detected (p > 0.05 in all cases). One patient died at day 70 with invasive histoplasmosis. No important adverse effects of Rituximab therapy were registered in other patients. A significant enhancement in the levels of different CD4+ regulatory cells (T(REG), Th3, Tr1), but not CD8+ Ts lymphocytes, was observed at day 30. This increase was sustained for T(REG )cells at day 90, and accompanied by an improvement in their regulatory function. In addition, we observed an unexpected increase in the apoptosis of T cells at day 30. Interestingly, the enhancement in the suppressive function of T(REG )cells was not observed in the two patients that showed the poorest clinical response to Rituximab. We conclude that the data obtained in this open clinical trial suggest that Rituximab is a promising candidate for randomized controlled trials in patients with lupus nephritis refractory to the conventional immunosuppressive therapy. The effects of Rituximab on regulatory cells and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic lupus erythematosis deserves additional studies.
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spelling pubmed-15266182006-08-04 Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study Vigna-Perez, Mónica Hernández-Castro, Berenice Paredes-Saharopulos, Octavio Portales-Pérez, Diana Baranda, Lourdes Abud-Mendoza, Carlos González-Amaro, Roberto Arthritis Res Ther Research Article We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an open clinical trial, 22 patients with active systemic lupus erythematosis and renal involvement (mainly class III and IV according to the WHO classification) that was refractory to conventional therapy were studied. In all these patients, Rituximab (0.5 to 1.0 g at days 1 and 15) was added to the immunosuppressive therapy and its therapeutic effect was evaluated. In addition, the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed. We found a significant reduction in disease activity (p < 0.05, MEX-SLEDAI index), and proteinuria (p < 0.05) at days 60 and 90 of Rituximab therapy. Although most patients showed improvement in creatinine clearance and erythrocyturia, no significant changes in these parameters were detected. In most patients (20/22), B cell depletion was observed, but no clear-cut effect of Rituximab on complement levels or auto-antibody titers was detected (p > 0.05 in all cases). One patient died at day 70 with invasive histoplasmosis. No important adverse effects of Rituximab therapy were registered in other patients. A significant enhancement in the levels of different CD4+ regulatory cells (T(REG), Th3, Tr1), but not CD8+ Ts lymphocytes, was observed at day 30. This increase was sustained for T(REG )cells at day 90, and accompanied by an improvement in their regulatory function. In addition, we observed an unexpected increase in the apoptosis of T cells at day 30. Interestingly, the enhancement in the suppressive function of T(REG )cells was not observed in the two patients that showed the poorest clinical response to Rituximab. We conclude that the data obtained in this open clinical trial suggest that Rituximab is a promising candidate for randomized controlled trials in patients with lupus nephritis refractory to the conventional immunosuppressive therapy. The effects of Rituximab on regulatory cells and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic lupus erythematosis deserves additional studies. BioMed Central 2006 2006-05-05 /pmc/articles/PMC1526618/ /pubmed/16677395 http://dx.doi.org/10.1186/ar1954 Text en Copyright © 2006 Vigna-Perez et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Vigna-Perez, Mónica
Hernández-Castro, Berenice
Paredes-Saharopulos, Octavio
Portales-Pérez, Diana
Baranda, Lourdes
Abud-Mendoza, Carlos
González-Amaro, Roberto
Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study
title Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study
title_full Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study
title_fullStr Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study
title_full_unstemmed Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study
title_short Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study
title_sort clinical and immunological effects of rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526618/
https://www.ncbi.nlm.nih.gov/pubmed/16677395
http://dx.doi.org/10.1186/ar1954
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