American Journal of Transplantation 2014; 14: 2668 Wiley Periodicals Inc.
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Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.12959
Letter to the Editor
Less Sensitization but Not Necessarily More Tolerance With Better Matching To the Editor: In the Letter to the Editor, R. J. Duquesnoy correctly asserts that the risk of sensitization and de novo antibody formation after allo-transplantation could be ameliorated with strategies that enhance HLA epitope similarity between donor and recipient (1). As an approach to reduce the incidence of sensitization and prolong graft half-life, matching at an epitope level would appear an important development. Sensitization represents a major barrier to both transient and durable chimerism due to the putative rapid immunemediated elimination of donor hematopoietic stem cells (HSCs) by recipient preformed antibody or anamnestic responses. This reduces the efficacy of current tolerance protocols and may make it considerably more difficult to achieve tolerance in a second allograft, even when donorspecific antibody is not detectable. The work of Kawai et al suggests that the time it takes to mount a primary immune response and reject the HSC graft may be sufficient to produce tolerance to the kidney allograft from the same donor in most but not all cases (2). Tolerance is a certainty among patients who successfully engraft and achieve full donor chimerism. Regardless of their degree of HLA mismatching they should not develop donor-specific allo-reactivity to what is essentially ‘‘self.’’ It is unclear at this time whether better HLA matching as could be achieved using epitope typing would make it more likely to achieve tolerance in the case of transient chimerism or engraftment when conditioning regimens are used that promote full donor chimerism. However, the degree of antigen mismatch may influence the risk of graft-versus-host disease
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(GVHD) in the setting of stable chimerism. There is now some evidence that tolerance can be successfully achieved with good rates of engraftment and low GVHD even when the donor and recipient are unrelated (3). R. A. Montgomery Department of Surgery John Hopkins University Baltimore, MD Corresponding author: Robert A. Montgomery, [email protected]
Disclosure The author of this manuscript has no conflicts of interest to disclose as described by the American Journal of Transplantation.
References 1. Duquesnoy RJ. HLA epitopes and tolerance induction protocols. Am J Transplant 2014; 14: 2667. 2. Kawai T, Cosimi AB, Spitzer TR, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 2008; 358: 353–361. 3. Leventhal J, Abecassis M, Miller J, et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. SciTransl Med 2012; 4: 12124ra28.
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Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.12959
Letter to the Editor
Less Sensitization but Not Necessarily More Tolerance With Better Matching To the Editor: In the Letter to the Editor, R. J. Duquesnoy correctly asserts that the risk of sensitization and de novo antibody formation after allo-transplantation could be ameliorated with strategies that enhance HLA epitope similarity between donor and recipient (1). As an approach to reduce the incidence of sensitization and prolong graft half-life, matching at an epitope level would appear an important development. Sensitization represents a major barrier to both transient and durable chimerism due to the putative rapid immunemediated elimination of donor hematopoietic stem cells (HSCs) by recipient preformed antibody or anamnestic responses. This reduces the efficacy of current tolerance protocols and may make it considerably more difficult to achieve tolerance in a second allograft, even when donorspecific antibody is not detectable. The work of Kawai et al suggests that the time it takes to mount a primary immune response and reject the HSC graft may be sufficient to produce tolerance to the kidney allograft from the same donor in most but not all cases (2). Tolerance is a certainty among patients who successfully engraft and achieve full donor chimerism. Regardless of their degree of HLA mismatching they should not develop donor-specific allo-reactivity to what is essentially ‘‘self.’’ It is unclear at this time whether better HLA matching as could be achieved using epitope typing would make it more likely to achieve tolerance in the case of transient chimerism or engraftment when conditioning regimens are used that promote full donor chimerism. However, the degree of antigen mismatch may influence the risk of graft-versus-host disease
2668
(GVHD) in the setting of stable chimerism. There is now some evidence that tolerance can be successfully achieved with good rates of engraftment and low GVHD even when the donor and recipient are unrelated (3). R. A. Montgomery Department of Surgery John Hopkins University Baltimore, MD Corresponding author: Robert A. Montgomery, [email protected]
Disclosure The author of this manuscript has no conflicts of interest to disclose as described by the American Journal of Transplantation.
References 1. Duquesnoy RJ. HLA epitopes and tolerance induction protocols. Am J Transplant 2014; 14: 2667. 2. Kawai T, Cosimi AB, Spitzer TR, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 2008; 358: 353–361. 3. Leventhal J, Abecassis M, Miller J, et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. SciTransl Med 2012; 4: 12124ra28.
