LABORATORY IMMUNOLOGY AND KIDNEY TRANSPLANTATION

J.P. Peräsaari¹, L. Kyllönen², K. Salmela², J. Merenmies^1
1Clinical Laboratory, Finnish Red Cross Blood Service, Helsinki/FINLAND, ²Department Of Surgery, Division Of Transplantation, Helsinki University Hospital, Helsinki/FINLAND

Body: Introduction: Donor specific HLA antibodies (DSA) form the major obstacle for a substantial part of patients suffering from chronic renal failure to receive a renal transplant. A negative lymphocyte cross match (XM) based on complement dependent cytotoxicity (CDC-XM) is sensitive enough to prevent hyperacute rejections and most of accelerated antibody-mediated rejections (AMR). However, sensitive solid phase antibody detection such as Luminex-based antibody identification has revealed that a number of CDC-XM negative patients have DSA's before transplantation. However, the clinical impact of DSA's detected only by Luminex are obscure. Methods: Serum samples were collected from 800 consecutive adult kidney transplant recipients during 2000-2004 on the day of transplant. All transplantations were performed after a negative CDC-XM using spleen-derived lymphocytes. Retrospective serum screening and identification of HLA-antibodies was performed with Luminex-based commercial kits (LABScreen, One Lambda Inc.). HLA typing of the patients and donors was performed with a CDC test (Biotest) and low resolution PCR-SSP (One Lambda). Additional typing with PCR-SSO (One Lambda) was performed to confirm donor specificity of an antibody. Rejection diagnosis was based on core biopsies classified according to the Banff 1997 classification. Results: Anti-HLA antibodies were detected in 275 patients (34%). DSA’s were found in 106 (13%) patients. Of the patients, 48 (6.0%) had Class I DSA and 38 (4.8%) had Class II DSA. Both Class I and Class II antibodies were detected in 20 (2.5%) patients. Of the patients with Class I antibodies, 38% had DSA. However, the patients with Class II antibodies were much more likely to have DSA, as 38 (95%) of 40 Class II Ab positive patients had DSA. The overall incidence of rejection was significantly higher among patients with Class II DSA than patients without DSA (NDSA) or with class I DSA only. In DSA II group 39.5% of the patients were diagnosed with rejection. In the DSA I and NDSA groups rejection incidences were 12.5% and 14.3%, respectively. In DSA I+II group the rejection incidence was comparable to DSA II group (35%). Also, the incidence of clinically important steroid resistant rejection (SRR) was significantly higher in DSA I+II group (20% p<0.001) and DSA II group (7.9% p<0.025 ) compared to NDSA or DSA I (2.0%) and (2.1 %) respectively. The patients with Class II DSA had significantly lower allograft survival (GS) (log-rank: p=0.005) than patients without DSA: The Kaplan-Meier estimate of 5-year GS in patients with DSA II was 77.5% vs 87.0 in NDSA patients. DSA I patients showed only a trend for worse GS compared to NDSA patients. Conclusion: In conclusion, the risk of rejection and graft loss is increased in patients having Class II DSA pre-transplant. However, the majority of the patients having DSA based on Luminex identification had excellent GS during ten year follow up. According to our data DSA detected by Luminex with negative CDC-XM is not a contraindication for renal transplantation. Instead, these patients should be carefully followed after TX.

Disclosure: All authors have declared no conflicts of interest.