Pre-Transplant Angiotensin II Type 1 Receptor Antibodies and Anti-Endothelial Cell Antibodies Predict Graft Function and Allograft Rejection in a Low-Risk Kidney Transplantation Setting
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Background: Non-HLA antibodies, anti-angiotensin II type 1 receptor antibodies (anti-AT1R) and anti-endothelial cell antibodies (AECA), are known to play a role in allograft rejection. We evaluated the role of both antibodies in predicting post-transplant outcomes in low-risk living donor kidney transplantation (LDKT) recipients. Methods: In 94 consecutive LDKT recipients who were ABO compatible and negative for pre-transplant HLA donor-specific antibodies, we determined the levels of anti-AT1Rs using an enzyme-linked immunosorbent assay and the presence of AECAs using a flow cytometric endothelial cell crossmatch (ECXM) assay with pre-transplant sera. Hazard ratio (HR) was calculated to predict post-transplant outcomes. Results: Pre-transplant anti-AT1Rs (≥11.5 U/mL) and AECAs were observed in 36 (38.3%) and 22 recipients (23.4%), respectively; 11 recipients had both. Pre-transplant anti-AT1Rs were a significant risk factor for the development of acute rejection (AR) (HR 2.09; P=0.018), while a positive AECA status was associated with AR or microvascular inflammation only (HR 2.47; P=0.004) throughout the follow-up period. In particular, AECA (+) recipients with ≥11.5 U/mL anti-AT1Rs exhibited a significant effect on creatinine and estimated glomerular filtration rate (P<0.001; P=0.028), although the risk of AR was not significant. Conclusions: Pre-transplant anti-AT1Rs and AECAs have independent negative effects on post-transplant outcomes in low-risk LDKT recipients. Assessment of both antibodies would be helpful in stratifying the pre-transplant immunological risk, even in low-risk LDKT recipients.
Abstract
Background: Non-HLA antibodies, anti-angiotensin II type 1 receptor antibodies (anti-AT1R) and anti-endothelial cell antibodies (AECA), are known to play a role in allograft rejection. We evaluated the role of both antibodies in predicting post-transplant outcomes in low-risk living donor kidney transplantation (LDKT) recipients. Methods: In 94 consecutive LDKT recipients who were ABO compatible and negative for pre-transplant HLA donor-specific antibodies, we determined the levels of anti-AT1Rs using an enzyme-linked immunosorbent assay and the presence of AECAs using a flow cytometric endothelial cell crossmatch (ECXM) assay with pre-transplant sera. Hazard ratio (HR) was calculated to predict post-transplant outcomes. Results: Pre-transplant anti-AT1Rs (≥11.5 U/mL) and AECAs were observed in 36 (38.3%) and 22 recipients (23.4%), respectively; 11 recipients had both. Pre-transplant anti-AT1Rs were a significant risk factor for the development of acute rejection (AR) (HR 2.09; P=0.018), while a positive AECA status was associated with AR or microvascular inflammation only (HR 2.47; P=0.004) throughout the follow-up period. In particular, AECA (+) recipients with ≥11.5 U/mL anti-AT1Rs exhibited a significant effect on creatinine and estimated glomerular filtration rate (P<0.001; P=0.028), although the risk of AR was not significant. Conclusions: Pre-transplant anti-AT1Rs and AECAs have independent negative effects on post-transplant outcomes in low-risk LDKT recipients. Assessment of both antibodies would be helpful in stratifying the pre-transplant immunological risk, even in low-risk LDKT recipients.
참고문헌 (27)
- Terasaki PI, "Humoral theory of transplantation", Am J Transplant, 3, pp.665~673 (2003)
- Opelz G, "Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies", Lancet, 365, pp.1570~1576 (2005)
- Han F, "Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection", Clin Chem Lab Med, 47, pp.1265~1269 (2009)
- Breimer ME, "Multicenter evaluation of a novel endothelial cell crossmatch test in kidney transplantation", Transplantation, 87, pp.549~556 (2009)
- Xavier P, "XM-ONE detection of endothelium cell antibodies identifies a subgroup of HLA-antibody negative patients undergoing acute rejection", Transplant Proc, 43, pp.91~94 (2011)
- Ronda C, "Non-human leukocyte antigen antibodies reactive with endothelial cells could be involved in early loss of renal allografts", Transplant Proc, 43, pp.1345~1348 (2011)
- Taniguchi M, "Higher risk of kidney graft failure in the presence of anti-angiotensin II type-1 receptor antibodies", Am J Transplant, 13, pp.2577~2589 (2013)
- Giral M, "Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss", Am J Transplant, 13, pp.2567~2576 (2013)
- Banasik M, "The influence of non-HLA antibodies directed against angiotensin II type 1 receptor(AT1R)on early renal transplant outcomes", Transpl Int, 27, pp.1029~1038 (2014)
- Banasik M, "Non-HLA antibodies: angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) are associated with renal allograft injury and graft loss", Transplant Proc, 46, pp.2618~2621 (2014)
- Jackson AM, "Endothelial cell antibodies associated with novel targets and increased rejection", J Am Soc Nephrol, 26, pp.1161~1171 (2015)
- Philogene MC, "Anti-angiotensin II Type 1 receptor and anti-endothelial cell antibodies: A cross-sectional analysis of pathological findings in allograft biopsies", Transplantation, 101, pp.608~615 (2017)
- Philogene MC, "Pre-transplant screening for non-HLA antibodies : who should be tested", Hum Immunol, 79, pp.195~202 (2018)
- Piotti G, "Vascular endothelium as a target of immune response in renal transplant rejection", Front Immunol, 5, pp.505~ (2014)
- Fuss A, "C4d-negative antibody-mediated rejection with high anti-angiotensin II type I receptor antibodies in absence of donor-specific antibodies", Nephrology (Carlton), 20, pp.467~473 (2015)
- 민지원, "Clinical Impact of Pre-transplant Antibodies Against Angiotensin II Type I Receptor and Major Histocompatibility Complex Class I-Related Chain A in Kidney Transplant Patients", Annals of Laboratory Medicine, 38(5), pp.450~457 (2018), 대한진단검사의학회[DOI]
- Reinsmoen NL, "Increased negative impact of donor HLA-specific together with non-HLA-specific antibodies on graft outcome", Transplantation, 97, pp.595~601 (2014)
- Haas M, "The Banff 2017 Kidney Meeting Report: revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials", Am J Transplant, 18, pp.293~307 (2018)
- Batal I, "Clinical significance of the distribution of C4d deposits in different anatomic compartments of the allograft kidney", Mod Pathol, 21, pp.1490~1498 (2008)
- Gibson IW, "Peritubular capillaritis in renal allografts: prevalence, scoring system, reproducibility and clinicopathological correlates", Am J Transplant, 8, pp.819~825 (2008)
- Gupta A, "Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies", Kidney Int, 89, pp.217~225 (2016)
- Daniel V, "Clinical relevance of preformed IgG and IgM antibodies against donor endothelial progenitor cells in recipients of living donor kidney grafts", Clin Transplant, 30, pp.124~130 (2016)
- Zitzner JR, "A prospective study evaluating the role of donor-specific anti-endothelial crossmatch (XM-ONE assay) in predicting living donor kidney transplant outcome", Hum Immunol, 74, pp.1431~1436 (2013)
- Gareau AJ, "Pre-transplant AT1R antibodies correlate with early allograft rejection", Transpl Immunol, 46, pp.29~35 (2018)
- In JW, "Anti-angiotensin type 1 receptor antibodies associated with antibody-mediated rejection in patients without preformed HLA-donor-specific antibody", Transplant Proc, 46, pp.3371~3374 (2014)
- Banasik M, "The impact of non-HLA antibodies directed against endothelin-1 type A receptors (ETAR) on early renal transplant outcomes", Transpl Immunol, 30, pp.24~29 (2014)
- Cuevas E, "Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies", Nephrol Dial Transplant, 31, pp.1738~1745 (2016)