ELISA AT1R

M. Taniguchi, L.M.Rebellato, J.Cai, J.Hopfield, K.P.Briley, C.E.Haisch, P.G.Catrou, P.Bolin, K.Parker, W.T.Kendrick, S.A.Kendrick, R.C.Harland and P.I.Terasaki

Reports have associated non-HLA antibodies, specifically those against angiotensin IItype-1receptor(AT1R), with antibody-mediated kidney graft rejection. However, association of anti-AT1R with graft failure had not been demonstrated. We tested anti-AT1R and donorspecific HLA antibodies(DSA) in pre-and posttransplant sera from 351 consecutive kidney recipients: 134 with biopsy-proven rejection and/or lesions (abnormal biopsy group [ABG]) and 217 control group (CG) patients. The ABG’s rate of anti-AT1R was significantly higher than the CG’s (18%vs. 6%, p<0.001). Moreover, 79% of ABG patients with anti-AT1R lost their rafts (vs. 0%, CG), anti-AT1R levels in 58% of those failed grafts increasing posttransplant. With anti-AT1R detectable before DSA, time to graft failure was 31 months—but 63 months with DSA detectable before anti-AT1R. Patients with both anti-AT1R and DSA had lower graft survival than those with DSA alone (log-rank p¼0.007). Multivariate analysis showed that de novo anti-AT1R was anindependent predictorof graft failure in theABG, alone (HR: 6.6), and in the entire population (HR: 5.4). In conclusion, this study found significant association of anti-AT1R with graft failure. Further study is needed to establish causality between anti-AT1R and graft failure and, thus, the importance of routine anti-AT1R monitoring and therapeutic targeting.

Keywords: Angiotensin II type-1 receptor antibodies, AT1R, DSA, kidney transplantation, rejection

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Comments

  • This paper followed patients with anti AT1R, DSA and graft failure. However, causality and reasons as to why some anti AT1R in some patients are more agonistic than other patients still remains unclear. I found it important to note that development of DSA and anti AT1R post transplant translated into lower graft survivial versus DSA or AT1R alone. It was interesting to discuss that about half of the patients with both pre and post transplant anti AT1R lost their grafts compared to one patient with only pre anti AT1R that lost his/her graft. My question is, for those patients who have anti AT1R pre transplant but do not have anti AT1R post transplant. What happens to the anti AT1R? This paper shows the importance of monitoring HLA and non HLA post transplant and the importance of pre transplant baselines.
  • With discussion from our researchers it is clear how AT1R testing could paint a better picture for risk of rejection. This is an exciting discovery that will change the scope of how we take care of our patients outside of HLA antibody mediated rejection.
  • This article and discussion helped improve my understanding of how non-HLA antibodies can effect transplantation. I have been running the AT1R ELISA for the past few months and knowing how the data is used gave me a better idea of the importance of monitoring patients for non-HLA.
  • I was aware that our lab currently runs the AT1R testing, but until this article and the discussion regarding its content, I was not familiar with its importance and use. I found the discussion regarding the difference between HLA and non HLA specific antibody quite interesting in their relationship to graft failure. My interpretation of the data suggesting a more rapid graft failure with a pre-transplant positive AT1R sample, regardless of HLA antibody, certainly suggests an increase importance in AT1R monitoring from a patient standpoint.
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