Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients
Abstract There is no established treatment for progressive IgA nephropathy refractory to steroids and immunosuppressant drugs (r-IgAN). Interleukin 17 (IL-17) blockade has garnered interest in immune-mediated diseases involving the gut-kidney axis. However, single IL-17A inhibition induced paradoxic...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-55425-7 |
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| author | Miguel G. Uriol-Rivera Aina Obrador-Mulet Maria Rosa Juliá Vanessa Daza-Cajigal Olga Delgado-Sanchez Angel Garcia Alvarez Ana Gomez-Lobon Paula Carrillo-Garcia Carlos Saus-Sarrias Cristina Gómez-Cobo Daniel Ramis-Cabrer Joan Gasco Company Javier Molina-Infante The Balear IgA Research and Treatment Project |
| author_facet | Miguel G. Uriol-Rivera Aina Obrador-Mulet Maria Rosa Juliá Vanessa Daza-Cajigal Olga Delgado-Sanchez Angel Garcia Alvarez Ana Gomez-Lobon Paula Carrillo-Garcia Carlos Saus-Sarrias Cristina Gómez-Cobo Daniel Ramis-Cabrer Joan Gasco Company Javier Molina-Infante The Balear IgA Research and Treatment Project |
| author_sort | Miguel G. Uriol-Rivera |
| collection | DOAJ |
| description | Abstract There is no established treatment for progressive IgA nephropathy refractory to steroids and immunosuppressant drugs (r-IgAN). Interleukin 17 (IL-17) blockade has garnered interest in immune-mediated diseases involving the gut-kidney axis. However, single IL-17A inhibition induced paradoxical effects in patients with Crohn’s disease and some cases of de novo glomerulonephritis, possibly due to the complete Th1 cell response, along with the concomitant downregulation of regulatory T cells (Tregs). Seven r-IgAN patients were treated with at least six months of oral paricalcitol, followed by the addition of subcutaneous anti-IL-17A (secukinumab). After a mean follow-up of 28 months, proteinuria decreased by 71% (95% CI: 56–87), P < 0.001. One patient started dialysis, while the annual eGFR decline in the remaining patients [mean (95% CI)] was reduced by 4.9 mL/min/1.73 m2 (95% CI: 0.1–9.7), P = 0.046. Circulating Th1, Th17, and Treg cells remained stable, but Th2 cells decreased, modifying the Th1/Th2 ratio. Intriguingly, accumulation of circulating Th17.1 cells was observed. This novel sequential therapy appears to optimize renal advantages in patients with r-IgAN and elicit alterations in potentially pathogenic T helper cells. |
| first_indexed | 2024-03-07T15:10:38Z |
| format | Article |
| id | doaj.art-ed42bbc09b42496f80578904f9f518a7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:10:38Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ed42bbc09b42496f80578904f9f518a72024-03-05T18:41:36ZengNature PortfolioScientific Reports2045-23222024-02-0114111110.1038/s41598-024-55425-7Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patientsMiguel G. Uriol-Rivera0Aina Obrador-Mulet1Maria Rosa Juliá2Vanessa Daza-Cajigal3Olga Delgado-Sanchez4Angel Garcia Alvarez5Ana Gomez-Lobon6Paula Carrillo-Garcia7Carlos Saus-Sarrias8Cristina Gómez-Cobo9Daniel Ramis-Cabrer10Joan Gasco Company11Javier Molina-Infante12The Balear IgA Research and Treatment ProjectNephrology Department, Hospital Universitario Son EspasesNephrology Department, Hospital Universitario Son EspasesImmunology Department, Hospital Universitario Son EspasesImmunology Department, Hospital Universitario Son EspasesPharmacy Department, Hospital Universitario Son EspasesPharmacy Department, Hospital Universitario Son EspasesPharmacy Department, Hospital Universitario Son EspasesPathology Department, Hospital Universitario Son EspasesPathology Department, Hospital Universitario Son EspasesLaboratory Medicine Department, Hospital Universitario Son EspasesFundació Institut d’Investigació Sanitària Illes Balears (IdISBa)Nephrology Department, Hospital Universitario Son EspasesGastroenterology Department, Hospital Universitario de CáceresAbstract There is no established treatment for progressive IgA nephropathy refractory to steroids and immunosuppressant drugs (r-IgAN). Interleukin 17 (IL-17) blockade has garnered interest in immune-mediated diseases involving the gut-kidney axis. However, single IL-17A inhibition induced paradoxical effects in patients with Crohn’s disease and some cases of de novo glomerulonephritis, possibly due to the complete Th1 cell response, along with the concomitant downregulation of regulatory T cells (Tregs). Seven r-IgAN patients were treated with at least six months of oral paricalcitol, followed by the addition of subcutaneous anti-IL-17A (secukinumab). After a mean follow-up of 28 months, proteinuria decreased by 71% (95% CI: 56–87), P < 0.001. One patient started dialysis, while the annual eGFR decline in the remaining patients [mean (95% CI)] was reduced by 4.9 mL/min/1.73 m2 (95% CI: 0.1–9.7), P = 0.046. Circulating Th1, Th17, and Treg cells remained stable, but Th2 cells decreased, modifying the Th1/Th2 ratio. Intriguingly, accumulation of circulating Th17.1 cells was observed. This novel sequential therapy appears to optimize renal advantages in patients with r-IgAN and elicit alterations in potentially pathogenic T helper cells.https://doi.org/10.1038/s41598-024-55425-7InflammationInterleukin-17AIgA nephropathyVitamin D receptor |
| spellingShingle | Miguel G. Uriol-Rivera Aina Obrador-Mulet Maria Rosa Juliá Vanessa Daza-Cajigal Olga Delgado-Sanchez Angel Garcia Alvarez Ana Gomez-Lobon Paula Carrillo-Garcia Carlos Saus-Sarrias Cristina Gómez-Cobo Daniel Ramis-Cabrer Joan Gasco Company Javier Molina-Infante The Balear IgA Research and Treatment Project Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients Scientific Reports Inflammation Interleukin-17A IgA nephropathy Vitamin D receptor |
| title | Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients |
| title_full | Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients |
| title_fullStr | Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients |
| title_full_unstemmed | Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients |
| title_short | Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients |
| title_sort | sequential administration of paricalcitol followed by il 17 blockade for progressive refractory iga nephropathy patients |
| topic | Inflammation Interleukin-17A IgA nephropathy Vitamin D receptor |
| url | https://doi.org/10.1038/s41598-024-55425-7 |
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