Anti-HLA class II antibodies and chronic allograft nephropathy

The purpose of this study was to prospectively analyze the relationship between posttransplant IgG anti-HLA class I and/or class II antibodies and graft failure due to chronic allograft nephropathy (CAN). We studied 512 first kidney graft recipients transplanted at a single center, with a graft functioning for at least 3 years. A single blood sample was collected from each patient, and the presence of antibodies was evaluated by PRA-ELISA. The median post-transplant time after blood collection was 4.4 years and did not differ between patients with or without anti-HLA antibodies. Among the 512 recipients, 55 (10.7%)were positive for anti-HLA class II, 20 (3.9%) for anti-HLAclass I, and 16 (3.1%) for anti-HLA class I and class II antibodies. After antibody evaluation, the patients were followed for at least 34 months. Anti-HLA class II antibodies and serum creatinine levels > or = 2 mg/dl at the time of antibody testing were independently associated with graft loss due to CAN, with relative risks (RR) of 3.29 and 13.82, respectively. When both factors were present, the RR rose to 36.07. In graft biopsies with CAN, the lesions believed to be mediated by antibodies (chronic glomerulopathy, arteriosclerosis, and lamination of the peritubular capillaries basement membrane) were more prevalent in biopsies with CAN from patients with anti-HLA class II antibodies. In conclusion, our data support not only an association but also a pathogenic role of anti-HLA class II antibodies in approximately 40% of chronic allograft cases.