Reversion of resistance to immunosuppressive agents in three patients with psoriatic arthritis by cyclosporine A: modulation of P-glycoprotein function.
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.
Department of Medical Sciences, Sapienza University of Rome, 2nd School of Medicine, S. Andrea University Hospital, Rome, Italy. pyke@inwind.it
Andrea Picchianti
AP
Diamanti
Manuela
M
Rosado
Valentina
V
Germano
Marco
M
Scarsella
Ezio
E
Giorda
Edoardo
E
Podestà
Raffaele
R
D'Amelio
Rita
R
Carsetti
Bruno
B
Laganà
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D015535:Arthritis, Psoriatic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D001799:Blood Sedimentation / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use*; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D020112:Rhodamine 123 / Q000378:metabolism; D012460:Sulfasalazine / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D020112:Rhodamine 123; D012460:Sulfasalazine; D016572:Cyclosporine; D002097:C-Reactive Protein; D014700:Verapamil; D008727:Methotrexate