Retrospective Analysis Of Antibody-Mediated Rejection In Renal Allograft Recipients

Objective: To study the potential high-risk factors, the pathological features, the clinical process and prognosis in antibody-mediated rejection (AMR) patients.Methods: 112 renal allograft recipients undertaken allograft biopsy from January 1994 to May 2007 were enrolled. Their paraffin sections were stained with polyclonal anti-C4d antibody and monoclonal anti-CD20 antibody. According to Banff 2005 diagnostic categories, there were 30 C4d-positive cases which were divided into two groups: the AAMR (Acute AMR) group including 19 cases and the CAMR (Chronic AMR) group including 11 cases; 35 cases of ATMR (Acute T-cell-Mediated Rejection) were recruited as the control group of AAMR meanwhile 26 cases of CTMR (Chronic active T-cell-Mediated Rejection) were recruited as the control group of CAMR. 18 cases after transplantation-unrelated nephrectomy were recruited as the negative control group. Then clinical information and biochemical data were collected and analyzed. Differences of clinical and histological changes between groups were evaluated by SPSS 13.0. A p value of less than 0.05 was considered significant.Results: 1. 35.2% of acute rejection cases and 29.7% of chronic rejection cases are C4d positive. 2. There is no significant difference of age, gender composing and allograft cold ischemia time between AMR and TMR group. 3. Glomerulitis, tubulitis, neutrophils invading peritubular capillary and vasculitis are common pathological appearance in both AAMR and ATMR biopsies. Peritubular capillary basement membrane multilayering may be a specific pathologic appearance of CAMR. 4. There is no significant relation between C4d-positive deposition and B-cell invading in renal allograft, but allografts with both C4d and CD20 positve deposition have significantly worse prognosis. 5. 9 of 19 (47.4%) AAMR cases got complete or partial relief, the 1 year recipient/allograft survival rate is 73.7%/68.4%, which is significantly worse than that of ATMR group. 7. None of 8 AAMR cases treated with single methylprednisolone (MP) protocol got complete relief, which indicates that MP has no therapeutic effect on AAMR. 8. Among 5 cases that received MP+ATG+IVIG treatment, 2 cases got complete relief, 2 cases died of severe pulmonary infection, the 1 year recipient/allograft survival rate is 60.0%/60.0%, which implies that although MP+ATG+IVIG combined protocol may have effect on reversing AAMR, it also resulted in higher risk of infections. None of 11 CAMR cases got relief, which demonstrates that there is no effective treatment for CAMR at present.Conclusion: Age, gender and allograft cold ischemia time are not responsible for AMR; Biopsy of AAMR allograft is short of typical pathological appearance while peritubular capillary basement membrane multilayering implies CAMR; There is no relation between C4d-positive deposition and B-cell invading in renal allografts, but allografts with both C4d and CD20 positve deposition have worse prognosis; Applying single MP protocol to cure AAMR has little effect; MP+ATG+IVIG combined protocol may have effect on reversing AAMR, but it has little effect on improving the long-term allograft survival. No effective treatment is found for CAMR in our study.