Assessment of immunosuppression by serum inhibition of alloreaction and measurement of cyclosporin A (CyA) serum levels in kidney graft recipients under CyA.
The immunosuppressive effect of kidney graft recipient sera was studied on T-lymphocyte alloreactive line (4H) proliferation and compared to native cyclosporin A (CyA) and CyA metabolite concentrations determined by radioimmunoassay (RIA) using specific or nonspecific monoclonal antibodies. Three clinical groups were studied: (1) patients experiencing acute renal rejection episodes (CyA-R), (2) patients experiencing CyA-dependent nephrotoxicity episodes (CyA-TOX) and (3) patients in a clinically steady state (CyA-ST), according to their therapeutic regimen i.e., monotherapy (CyA alone) or polytherapy (CyA associated with prednisolone and/or azathioprine). Regardless of the clinical state, sera of patients in polytherapy displayed more inhibitory activity than those of monotherapy patients (24% and 40% inhibition of 4H proliferation, respectively, at sera dilution of 1:2), something which was no doubt due to the inhibitory activity of prednisolone on T-lymphocyte growth. In the two therapeutic regimens, CyA-ST patient sera exhibited the lowest inhibitory activity on the 4H line (45% and 65% inhibition of 4H proliferation in mono- and polytherapy, respectively, at sera dilution of 1:2). Sera from CyA-TOX patients were highly inhibitory (74% and 86% inhibition of 4H proliferation in mono- and polytherapy, respectively, at sera dilution of 1:2), in agreement with RIA assays showing increased native circulating CyA and CyA metabolites and daily CyA intake in this group as compared to CyA-ST. Surprisingly, CyA-R patient sera were no less inhibitory than those of CyA-ST patients on 4H-line, antigen-induced proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
Chabannes
D
D
Unité INSERM 211, Unité de Recherche sur les effecteurs lymphocytaires T, Faculté de Médecine, Nantes, France.
Vernillet
L
L
Cantarovich
D
D
Humbert
H
H
Vie
H
H
Soulillou
J P
JP
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003524:Cyclosporins / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000187:drug effects; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007519:Isoantigens / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged
D003524:Cyclosporins; D007519:Isoantigens; D001379:Azathioprine; D008775:Methylprednisolone