Insensitivity to cyclosporine may explain the HLA-DRw6 recipient effect.
Clinical as well as experimental studies have found an interindividual variability in the immunosuppressive effect of cyclosporine (CsA). In renal transplant patients treated with CsA and prednisolone alone, biopsy-verified rejections were significantly more frequent in DRw6-positive than in DRw6-negative graft recipients. The relative risk for developing a graft rejection independently of the CsA blood levels increased in HLA-DRw6-positive transplant patients. Although no statistical significance of the CsA levels within different DR phenotypes could be assessed, HLA-DR2-positive graft recipients with biopsy-verified rejection episodes had significantly lower CsA levels than DR2-negative patients (P = 0.01). Our results would indicate a very low CsA sensitivity of HLA-DRw6-positive graft recipients and might explain previous results describing an increased incidence of rejection and decreased graft survival rates in these patients.
Kudlacek
S
S
2nd Department of Medicine, Institute of Immunology, University of Vienna, Vienna, Austria.
Zlabinger
G J
GJ
Pohanka
E
E
Hamilton
G
G
Rosenmayr
A
A
Kovarik
J
J
D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use*; D004351:Drug Resistance / Q000276:immunology*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000453:epidemiology* / Q000517:prevention & control; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D015236:HLA-C Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D016853:Muromonab-CD3 / Q000627:therapeutic use
D000961:Antilymphocyte Serum; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine