Reversion of resistance to immunosuppressive agents in three patients with psoriatic arthritis by cyclosporine A: Modulation of P-glycoprotein function

Andrea Picchianti Diamanti, Manuela Rosado, Valentina Germano, Marco Scarsella, Ezio Giorda, Edoardo Podestà, Raffaele D'Amelio, Rita Carsetti, Bruno Laganà

Research output: Contribution to journalArticle

Abstract

Secondary resistance may be a major problem in the management of autoimmune diseases. P-glycoprotein (P-gp) over-function has been described as a mechanism of drug resistance in autoimmune patients. P-gp function can in vitro be inhibited by cyclosporine A (CSA) and verapamil; moreover, P-gp reduction by CSA in systemic lupus erythematosus and rheumatoid arthritis has been demonstrated. Here, P-gp function before and after CSA administration in three psoriatic arthritis (PsA) patients, who developed a resistance to MTX/SSA, has been evaluated. P-gp function on patient cells was analyzed by measuring the changes in rhodamine-123 (Rh-123) fluorescence after verapamil incubation. CSA treatment resulted in good clinical outcome that was related with a significant P-gp function reduction at CD3+ and CD8+ levels. In addition to its immunosuppressive activity, CSA results may also be related to MTX/SSA effect restoration through P-gp inhibition. This is the first time that CSA has been demonstrated as being able to revert MTX/SSA resistance in PsA.

Original languageEnglish
Pages (from-to)9-13
Number of pages5
JournalClinical Immunology
Volume138
Issue number1
DOIs
Publication statusPublished - Jan 2011

Keywords

  • Cyclosporine
  • Drug resistance
  • P-glycoprotein
  • Rhodamine-123

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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