American Journal of Transplantation 2015; 15: 1727 Wiley Periodicals Inc.
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Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.13257
Letter to the Editor
Potential Hurdles to ABO-Incompatible Living Donor Kidney Transplantation Without Augmented Immunosuppression To the Editor: I read with interest the recent work by Masterson et al (1) reporting a successful case series of ABO-incompatible nonA2 living donor kidney transplantations (ABOi-LDKT). Transplanting low-isoagglutinin titer recipients without any special preparatory regimen would definitively pave the way to safer, cheaper and less invasive ABOi organ transplantations, and will increase solutions in paired exchange pools (5). Nevertheless, until initiation of mycophenolate mofetil 7–14 days before transplantation will be judged unnecessary, application of this ABOi protocol to recipients on deceased donor lists would remain impracticable. Furthermore, I feel that several technical details could undermine the conclusions of such protocol, and I kindly suggest the authors to perform additional investigations on their cohort.
In Table 3, the authors confirm the lack of correlation among isoagglutinin titers determined using the tube, Ortho and Diamed gel-card methods. It is known that even under standardized procedures, the tube test has an interlaboratory variation of 3–8 dilutions, while the gelcard methods have only 1 dilution variation. Flow cytometry titration performs even better and has virtually no variation (2). Implementation of the most exact isoagglutinin titration method in future ABOi-LDKT trials is now even more mandatory given the implications for avoidance of augmented immunosuppression. In 13% of the general population, a subset of anti-A/B IgG2 targets the combined structure of the terminal trisaccharide (which determines the A or B blood group) plus the H carbohydrate core chain. Four different types of H chain co-exist on erythrocytes; on the contrary, vascular endothelium expresses only type 2 chains. The direct consequence of this phenomenon is that by measuring the overall isoagglutinin titer on erythrocytes, we are including innocuous anti-type 1/3/4 ‘‘donorspecific’’ but not ‘‘graft-specific’’ isohemagglutinin, hence, overestimating the risk in 13% of recipients. In order to avoid such an overestimate, an ELISA-based titration method has been recently developed to differentiate chain type-specific anti-A and anti-B (3), and its implementation would be highly beneficial.
Some antigenic epitopes in individual A or B antigens are not present in AB antigen and vice versa. Accordingly, using commercial, exclusively A or B erythrocytes to titer anti-AB isohemagglutinins can lead to titer overestimates (5). So, in the four AB to A/B transplantations, the authors report (1), it should have been advisable to titer anti-AB isohemagglutinins using commercial or donorderived AB erythrocytes. In healthy individuals, most anti-A and anti-B IgGs are of the IgG2 and IgG4 subclasses, i.e. do not fix complement. It would then be interesting to learn the relative anti-B IgG subclass composition before transplantation and at the time of rejection in the single patient (a) who developed accelerated antibody-mediated rejection and C4d deposition versus the other 19 who intriguingly did not develop C4d deposition (1). D. Focosi* North-Western Tuscany Blood Bank, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy *Corresponding author: Daniele Focosi, [email protected]
Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
References 1. Masterson R, Hughes P, Walker RG, et al. ABO incompatible renal transplantation without antibody removal using conventional immunosuppression alone. Am J Transplant 2014; 14: 2807–2813. 2. Tanabe K. Interinstitutional variation in the measurement of anti-A/B antibodies: The Japanese ABO-Incompatible Transplantation Committee survey. Transplantation 2007; 84: S13–S16. 3. Lindberg L, Johansson SM, Liu J, Grufman P, Holgersson J. Is there a clinical need for a diagnostic test allowing detection of chain typespecific anti-A and anti-B? Transfusion 2011; 51: 494–503. 4. Jeyakanthan M, West LJ. Donor-specific isohemagglutinins: Measuring the unknown. Am J Transplant 2012; 12: 803–805. 5. Ferrari P, Hughes PD, Cohney SJ, Woodroffe C, Fidler S, D’Orsogna L. ABO-incompatible matching significantly enhances transplant rates in kidney paired donation. Transplantation 2013; 96: 821–826.
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Copyright of American Journal of Transplantation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
C
Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.13257
Letter to the Editor
Potential Hurdles to ABO-Incompatible Living Donor Kidney Transplantation Without Augmented Immunosuppression To the Editor: I read with interest the recent work by Masterson et al (1) reporting a successful case series of ABO-incompatible nonA2 living donor kidney transplantations (ABOi-LDKT). Transplanting low-isoagglutinin titer recipients without any special preparatory regimen would definitively pave the way to safer, cheaper and less invasive ABOi organ transplantations, and will increase solutions in paired exchange pools (5). Nevertheless, until initiation of mycophenolate mofetil 7–14 days before transplantation will be judged unnecessary, application of this ABOi protocol to recipients on deceased donor lists would remain impracticable. Furthermore, I feel that several technical details could undermine the conclusions of such protocol, and I kindly suggest the authors to perform additional investigations on their cohort.
In Table 3, the authors confirm the lack of correlation among isoagglutinin titers determined using the tube, Ortho and Diamed gel-card methods. It is known that even under standardized procedures, the tube test has an interlaboratory variation of 3–8 dilutions, while the gelcard methods have only 1 dilution variation. Flow cytometry titration performs even better and has virtually no variation (2). Implementation of the most exact isoagglutinin titration method in future ABOi-LDKT trials is now even more mandatory given the implications for avoidance of augmented immunosuppression. In 13% of the general population, a subset of anti-A/B IgG2 targets the combined structure of the terminal trisaccharide (which determines the A or B blood group) plus the H carbohydrate core chain. Four different types of H chain co-exist on erythrocytes; on the contrary, vascular endothelium expresses only type 2 chains. The direct consequence of this phenomenon is that by measuring the overall isoagglutinin titer on erythrocytes, we are including innocuous anti-type 1/3/4 ‘‘donorspecific’’ but not ‘‘graft-specific’’ isohemagglutinin, hence, overestimating the risk in 13% of recipients. In order to avoid such an overestimate, an ELISA-based titration method has been recently developed to differentiate chain type-specific anti-A and anti-B (3), and its implementation would be highly beneficial.
Some antigenic epitopes in individual A or B antigens are not present in AB antigen and vice versa. Accordingly, using commercial, exclusively A or B erythrocytes to titer anti-AB isohemagglutinins can lead to titer overestimates (5). So, in the four AB to A/B transplantations, the authors report (1), it should have been advisable to titer anti-AB isohemagglutinins using commercial or donorderived AB erythrocytes. In healthy individuals, most anti-A and anti-B IgGs are of the IgG2 and IgG4 subclasses, i.e. do not fix complement. It would then be interesting to learn the relative anti-B IgG subclass composition before transplantation and at the time of rejection in the single patient (a) who developed accelerated antibody-mediated rejection and C4d deposition versus the other 19 who intriguingly did not develop C4d deposition (1). D. Focosi* North-Western Tuscany Blood Bank, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy *Corresponding author: Daniele Focosi, [email protected]
Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
References 1. Masterson R, Hughes P, Walker RG, et al. ABO incompatible renal transplantation without antibody removal using conventional immunosuppression alone. Am J Transplant 2014; 14: 2807–2813. 2. Tanabe K. Interinstitutional variation in the measurement of anti-A/B antibodies: The Japanese ABO-Incompatible Transplantation Committee survey. Transplantation 2007; 84: S13–S16. 3. Lindberg L, Johansson SM, Liu J, Grufman P, Holgersson J. Is there a clinical need for a diagnostic test allowing detection of chain typespecific anti-A and anti-B? Transfusion 2011; 51: 494–503. 4. Jeyakanthan M, West LJ. Donor-specific isohemagglutinins: Measuring the unknown. Am J Transplant 2012; 12: 803–805. 5. Ferrari P, Hughes PD, Cohney SJ, Woodroffe C, Fidler S, D’Orsogna L. ABO-incompatible matching significantly enhances transplant rates in kidney paired donation. Transplantation 2013; 96: 821–826.
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Copyright of American Journal of Transplantation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
