Clinical significance of the presence of antihuman leukocyte antigen-donor specific antibody in kidney transplant recipients with allograft dysfunction
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Background/Aims: This study investigated the clinical significance of detecting anti-human leukocyte antigen-donor specific antibody (HLA-DSA) in kidney transplant recipients (KTRs) requiring indication biopsy owing to allograft dysfunction. Methods: We analyzed the presence of HLA-DSA in 210 KTRs who took indication biopsy. We divided these cases into two groups, HLA-DSA (+) (n = 52) and HLA-DSA (–) (n = 158) group, and compared the clinical characteristics, pathological findings, and clinical outcomes of the two groups. Results: The rates of retransplant, pretransplant sensitization, and HLA-mismatch were significantly higher in HLA-DSA (+) group than in HLA-DSA (–) group (p < 0.05 for each comparison). In histologic finding, all types of rejections were more frequent in the former group. Besides, scores of both the T-cell injury markers such as tubulitis, interstitial inf lammation, and vasculitis and antibody- mediated injury markers such as peritubular C4d deposition and microvascular inflammation (glomerulitis plus peritubular capillaritis) were higher in HLA-DSA (+) group (p < 0.05 for each). Notably, allograft outcomes were worse in HLA-DSA (+) group. Further, multivariate analysis showed that presence of HLADSA, advanced interstitial fibrosis/tubular atrophy (interstitial fibrosis plus tubular atrophy ≥ 2), and allograft rejection in biopsy were independent risk factors for allograft failure. Conclusions: The results of this study showed that presence of HLA-DSA in a case of allograft dysfunction adversely influences allograft outcome, and its detection, irrespective of the result of the allograft biopsy, necessitates intensive monitoring and treatment.
Abstract
Background/Aims: This study investigated the clinical significance of detecting anti-human leukocyte antigen-donor specific antibody (HLA-DSA) in kidney transplant recipients (KTRs) requiring indication biopsy owing to allograft dysfunction. Methods: We analyzed the presence of HLA-DSA in 210 KTRs who took indication biopsy. We divided these cases into two groups, HLA-DSA (+) (n = 52) and HLA-DSA (–) (n = 158) group, and compared the clinical characteristics, pathological findings, and clinical outcomes of the two groups. Results: The rates of retransplant, pretransplant sensitization, and HLA-mismatch were significantly higher in HLA-DSA (+) group than in HLA-DSA (–) group (p < 0.05 for each comparison). In histologic finding, all types of rejections were more frequent in the former group. Besides, scores of both the T-cell injury markers such as tubulitis, interstitial inf lammation, and vasculitis and antibody- mediated injury markers such as peritubular C4d deposition and microvascular inflammation (glomerulitis plus peritubular capillaritis) were higher in HLA-DSA (+) group (p < 0.05 for each). Notably, allograft outcomes were worse in HLA-DSA (+) group. Further, multivariate analysis showed that presence of HLADSA, advanced interstitial fibrosis/tubular atrophy (interstitial fibrosis plus tubular atrophy ≥ 2), and allograft rejection in biopsy were independent risk factors for allograft failure. Conclusions: The results of this study showed that presence of HLA-DSA in a case of allograft dysfunction adversely influences allograft outcome, and its detection, irrespective of the result of the allograft biopsy, necessitates intensive monitoring and treatment.
참고문헌 (31)
- Wiebe C, "Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant", Am J Transplant, 12, pp.1157~1167 (2012)[DOI]
- Lee PC, "All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies", Transplantation, 74, pp.1192~1194 (2002)[DOI]
- Sellares J, "Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence", Am J Transplant, 12, pp.388~399 (2012)[DOI]
- Cosio FG, "Transplant glomerulopathy", Am J Transplant, 8, pp.492~496 (2008)[DOI]
- Everly MJ, "Incidence and impact of de novo donor-specific alloantibody in primary renal allografts", Transplantation, 95, pp.410~417 (2013)[DOI]
- Dieplinger G, "Impact of de novo donor-specific HLA antibodies detected by Luminex solid-phase assay after transplantation in a group of 88 consecutive living-donor renal transplantations", Transpl Int, 27, pp.60~68 (2014)[DOI]
- Dieplinger G, "Changes in successive measures of de novo donor-specific anti-human leukocyte antigen antibodies intensity and the development of allograft dysfunction", Transplantation, 98, pp.1097~1104 (2014)[DOI]
- Chung BH, "Comparison of clinical outcome between high and low baseline anti-ABO antibody titers in ABO-incompatible kidney transplantation", Ren Fail, 33, pp.150~158 (2011)[DOI]
- Solez K, "Banff 07 classification of renal allograft pathology: updates and future directions", Am J Transplant, 8, pp.753~760 (2008)[DOI]
- Haas M, "Banff 2013 meeting report: inclusion of C4d-negative antibody-mediated rejection and antibody-associated arterial lesions", Am J Transplant, 14, pp.272~283 (2014)[DOI]
- Cooper JE, "Clinical significance of post kidney transplant de novo DSA in otherwise stable grafts", Clin Transpl, pp.359~364 (2011)
- Chung BH, "Clinical impact of the baseline donor-specific anti-human leukocyte antigen antibody measured by Luminex single antigen assay in living donor kidney transplant recipients after desensitization therapy", Transpl Int, 27, pp.49~59 (2014)[DOI]
- Chung BH, "Impact of ABO incompatibility on the development of acute antibody-mediated rejection in kidney transplant recipients presensitized to HLA", PLoS One, 10, pp.e0123638~ (2015)[DOI]
- Armstrong KA, "Obesity is associated with worsening cardiovascular risk factor profiles and proteinuria progression in renal transplant recipients", Am J Transplant, 5, pp.2710~2718 (2005)[DOI]
- Vlad G, "Relevance of different antibody detection methods for the prediction of antibody- mediated rejection and deceased-donor kidney allograft survival", Hum Immunol, 70, pp.589~594 (2009)[DOI]
- Caro-Oleas JL, "Clinical relevance of HLA donor-specific antibodies detected by single antigen assay in kidney transplantation", Nephrol Dial Transplant, 27, pp.1231~1238 (2012)[DOI]
- Hwang HS, "Antibody monitoring system to support the single-antigen Luminex assay in donor-specific antibody detection", Hum Immunol, 73, pp.370~375 (2012)[DOI]
- Ntokou IS, "Long-term follow up for anti-HLA donor specific antibodies postrenal transplantation: high immunogenicity of HLA class II graft molecules", Transpl Int, 24, pp.1084~1093 (2011)[DOI]
- Gloor JM, "Histologic findings one year after positive crossmatch or ABO blood group incompatible living donor kidney transplantation", Am J Transplant, 6, pp.1841~1847 (2006)[DOI]
- Ishida H, "Influence of preoperative anti-HLA antibodies on shortand long-term graft survival in recipients with or without rituximab treatment", Transpl Int, 27, pp.371~382 (2014)[DOI]
- Lachmann N, "Anti-human leukocyte antigen and donor-specific antibodies detected by luminex posttransplant serve as biomarkers for chronic rejection of renal allografts", Transplantation, 87, pp.1505~1513 (2009)[DOI]
- Nankivell BJ, "The natural history of chronic allograft nephropathy", N Engl J Med, 349, pp.2326~2333 (2003)[DOI]
- Thomas WR, "T and B cell responses to HDM allergens and antigens", Immunol Res, 37, pp.187~199 (2007)[DOI]
- Ramiscal RR, "T-cell subsets in the germinal center", Immunol Rev, 252, pp.146~155 (2013)[DOI]
- Qi H, "From SAP-less T cells to helpless B cells and back: dynamic T-B cell interactions underlie germinal center development and function", Immunol Rev, 247, pp.24~35 (2012)[DOI]
- Naemi FM, "Anti-donor HLA class I antibodies: pathways to endothelial cell activation and cell-mediated allograft rejection", Transplantation, 96, pp.258~266 (2013)[DOI]
- Lobo LJ, "Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation", J Heart Lung Transplant, 32, pp.70~97 (2013)[DOI]
- Sis B, "A new diagnostic algorithm for antibody-mediated microcirculation inflammation in kidney transplants", Am J Transplant, 12, pp.1168~1179 (2012)[DOI]
- de Kort H, "Microcirculation inflammation associates with outcome in renal transplant patients with de novo donor-specific antibodies", Am J Transplant, 13, pp.485~492 (2013)[DOI]
- Loupy A, "The impact of donor-specific anti-HLA antibodies on late kidney allograft failure", Nat Rev Nephrol, 8, pp.348~357 (2012)
- Aubert V, "Low levels of human leukocyte antigen donor-specific antibodies detected by solid phase assay before transplantation are frequently clinically irrelevant", Hum Immunol, 70, pp.580~583 (2009)[DOI]
