- Email: [email protected]
Potential Benefits of Antigen Reduction in Heart Valve Allografts
CORRESPONDENCE
The publication by Feingold and colleagues [1] concerning the expression of blood group antigens in cryopreserved allografts confirms the findings of Kadner and colleagues [2] in aortic and mitral allografts that was published earlier than the referenced citation [3]. Both groups conclude that (1) the microvascular endothelial cells of human heart valve conduits and myocardium express blood group antigens, whereas luminal endothelium does not, and (2) cryopreservation preserves the microvascular endothelial cells. Kadner and colleagues [2, 3] conclude that the absence of blood group-expressing cells precludes the need for blood group matching of heart valve donor tissue with recipients. Feingold and colleagues [1] allow that this antigen mismatch may affect valve durability. Evidence that blood group matching improves valve performance has been difficult to obtain, even as a definitive role for mismatched tissue antigens (MCH-I and MCH-II) is yet to be clearly defined. The strongest positive correlation comes from blood group matched and mismatched pediatric recipients [4, 5]. Given the immunogenicity of cryopreserved cardiac allografts, we agree with the Invited Commentator [6] that decellularization of allograft valve tissue would be an important step in the search for an optimal tissue-based implant. Our proprietary decellularization method called SynerGraft (CryoLife Inc, Kennesaw, GA) substantially reduces histologically demonstrable cells and class I and class II major histocompatibility antigens of aortic and pulmonary valves [7]. The role of the endothelium and possibly fibroblasts in the stimulation of an immune response has long been thought of importance to valve durability [8]. In the midterm, development of panel reactive antibodies in SynerGraft valve recipients is markedly diminished, while valve performance is maintained [9]. William F. Northrup III, MD Steven Goldstein, PhD CryoLife, Inc 1655 Roberts Blvd, NW Kennesaw, GA 30144 e-mail: [email protected]
References 1. Feingold B, Wearden PD, Morell VO, Galvis D, Galambos C. Expression of A and B blood group antigens on cryopreserved homografts. Ann Thorac Surg 2009;87:211– 4. 2. Kadner A, Chen RH, Mitchell RN, Adams DH. Lack of ABH-antigen expression on human cardiac valves. J Heart Valve Dis 2000;9:512– 6. 3. Kadner A, Chen RH, Mitchell RN, Adams DH. Homograft crossmatching is unnecessary due to the absence of blood group antigens. Ann Thorac Surg 2001;71:S349 –52. 4. Shaddy RE, Hunter D, Osborn KA, et al. Heart disease in the young: Prospective analysis of HLA immunogenicity of cryopreserved valve allografts used in pediatric heart surgery. Circulation 1996;94:1063–7. 5. Baskett RJ, Nanton MA, Warren AE, Ross DB. Human leukocyte antigen-DR and ABO mismatch are associated with accelerated homograft valve failure in children: implications for therapeutic interventions. J Thorac Cardiovasc Surg 2003; 126:232–9. 6. Jacobs ML. Invited Commentary. Ann Thorac Surg 2009;87: 214 –5. 7. Elkins RC, Dawson PE, Goldstein S, Walsh SP, Black KS. Decellularized human valve allografts. Ann Thorac Surg 2001;71(5 Suppl):S428 –32. © 2010 by The Society of Thoracic Surgeons Published by Elsevier Inc
8. Yankah AC, Wottge HU, Muller-Hermelink HK, et al. Transplantation of aortic and pulmonary allografts, enhanced viability of endothelial cells by cryopreservation, importance of histocompatibility. J Card Surg 1987;2(1 Suppl):209 –20. 9. Brown JW, Elkins RC, Clarke DR, et al. Performance of the CryoValve SG human decellularized pulmonary valve in 342 patients compared to the conventional CryoValve at a mean follow-up of 4 years. J Thorac Cardiovasc Surg [in press].
Drs Northrup and Goldstein disclose that they have a financial relationship with CryoLife Inc.
Reply To the Editor: We would like to thank Drs Northrup and Goldstein [1] for their interest in our work [2], and we appreciate the editor for giving us the opportunity to reply. We disagree with Drs Northrup and Goldstein’s assertion that our findings of A and B blood group antigen expression on human cryopreserved pulmonary homografts simply reaffirm those of others. The cited works of Kadner and colleagues [3, 4] reported expression of blood group antigens in the context of a preserved microvasculature endothelium on freshly explanted “myocardial tissue” and cryopreserved “septal myocardial tissue.” They also reported intact endothelium without blood group antigen expression on freshly harvested human cardiac valve leaflets and no blood group antigen expression nor intact endothelium on cryopreserved valve leaflets. In addition, we found no report in the literature detailing the expression of blood group antigens on homograft conduit (vessel) microvasculature. Thus, our findings of blood group A and B antigen expression and preservation of cryopreserved homograft conduit microvasculature (vasa vasorum) endothelium are indeed unique. We do agree with Dr Jacobs, who wrote the invited comment on our article [5], and with Drs Northrup and Goldstein that an optimal tissue-based implant would lack immunogenicity. Putting aside the issue of whether an immune response to blood group and/or major histocompatibility complex antigens expressed on the homograft microvasculature affects homograft longevity, a significant proportion of children with homograft exposure ultimately require heart transplantation. Many are highly allosensitized, which poses a significant barrier to transplantation [6 – 8]. This problem is likely to grow during the next 10 to 20 years as the initial waves of patients who have been surgical successes in staged single-ventricle palliation reach adolescence or young adulthood and present with end-stage ventricular dysfunction. Although data showing decreased antigen expression on and low panel reactive antibody response to decellularized homografts are encouraging [9], analysis with modern, highly sensitive alloantibody detection techniques (eg, Luminex; Luminex Corp, Austin, TX) would be most indicative of whether or not decellularized homograft is immunogenic. Brian Feingold, MD, MS Peter D. Wearden, MD, PhD Victor O. Morell, MD Daniel Galvis, BS, Pa (Ascp) Csaba Galambos, MD, PhD Children’s Hospital of Pittsburgh of UPMC University of Pittsburgh Medical Center 4401 Penn Ave Pittsburgh, PA 15224 e-mail: [email protected] Ann Thorac Surg 2010;90:357– 63 • 0003-4975/$36.00 doi:10.1016/j.athoracsur.2009.08.044
MISCELLANEOUS
Potential Benefits of Antigen Reduction in Heart Valve Allografts To the Editor:
The publication by Feingold and colleagues [1] concerning the expression of blood group antigens in cryopreserved allografts confirms the findings of Kadner and colleagues [2] in aortic and mitral allografts that was published earlier than the referenced citation [3]. Both groups conclude that (1) the microvascular endothelial cells of human heart valve conduits and myocardium express blood group antigens, whereas luminal endothelium does not, and (2) cryopreservation preserves the microvascular endothelial cells. Kadner and colleagues [2, 3] conclude that the absence of blood group-expressing cells precludes the need for blood group matching of heart valve donor tissue with recipients. Feingold and colleagues [1] allow that this antigen mismatch may affect valve durability. Evidence that blood group matching improves valve performance has been difficult to obtain, even as a definitive role for mismatched tissue antigens (MCH-I and MCH-II) is yet to be clearly defined. The strongest positive correlation comes from blood group matched and mismatched pediatric recipients [4, 5]. Given the immunogenicity of cryopreserved cardiac allografts, we agree with the Invited Commentator [6] that decellularization of allograft valve tissue would be an important step in the search for an optimal tissue-based implant. Our proprietary decellularization method called SynerGraft (CryoLife Inc, Kennesaw, GA) substantially reduces histologically demonstrable cells and class I and class II major histocompatibility antigens of aortic and pulmonary valves [7]. The role of the endothelium and possibly fibroblasts in the stimulation of an immune response has long been thought of importance to valve durability [8]. In the midterm, development of panel reactive antibodies in SynerGraft valve recipients is markedly diminished, while valve performance is maintained [9]. William F. Northrup III, MD Steven Goldstein, PhD CryoLife, Inc 1655 Roberts Blvd, NW Kennesaw, GA 30144 e-mail: [email protected]
References 1. Feingold B, Wearden PD, Morell VO, Galvis D, Galambos C. Expression of A and B blood group antigens on cryopreserved homografts. Ann Thorac Surg 2009;87:211– 4. 2. Kadner A, Chen RH, Mitchell RN, Adams DH. Lack of ABH-antigen expression on human cardiac valves. J Heart Valve Dis 2000;9:512– 6. 3. Kadner A, Chen RH, Mitchell RN, Adams DH. Homograft crossmatching is unnecessary due to the absence of blood group antigens. Ann Thorac Surg 2001;71:S349 –52. 4. Shaddy RE, Hunter D, Osborn KA, et al. Heart disease in the young: Prospective analysis of HLA immunogenicity of cryopreserved valve allografts used in pediatric heart surgery. Circulation 1996;94:1063–7. 5. Baskett RJ, Nanton MA, Warren AE, Ross DB. Human leukocyte antigen-DR and ABO mismatch are associated with accelerated homograft valve failure in children: implications for therapeutic interventions. J Thorac Cardiovasc Surg 2003; 126:232–9. 6. Jacobs ML. Invited Commentary. Ann Thorac Surg 2009;87: 214 –5. 7. Elkins RC, Dawson PE, Goldstein S, Walsh SP, Black KS. Decellularized human valve allografts. Ann Thorac Surg 2001;71(5 Suppl):S428 –32. © 2010 by The Society of Thoracic Surgeons Published by Elsevier Inc
8. Yankah AC, Wottge HU, Muller-Hermelink HK, et al. Transplantation of aortic and pulmonary allografts, enhanced viability of endothelial cells by cryopreservation, importance of histocompatibility. J Card Surg 1987;2(1 Suppl):209 –20. 9. Brown JW, Elkins RC, Clarke DR, et al. Performance of the CryoValve SG human decellularized pulmonary valve in 342 patients compared to the conventional CryoValve at a mean follow-up of 4 years. J Thorac Cardiovasc Surg [in press].
Drs Northrup and Goldstein disclose that they have a financial relationship with CryoLife Inc.
Reply To the Editor: We would like to thank Drs Northrup and Goldstein [1] for their interest in our work [2], and we appreciate the editor for giving us the opportunity to reply. We disagree with Drs Northrup and Goldstein’s assertion that our findings of A and B blood group antigen expression on human cryopreserved pulmonary homografts simply reaffirm those of others. The cited works of Kadner and colleagues [3, 4] reported expression of blood group antigens in the context of a preserved microvasculature endothelium on freshly explanted “myocardial tissue” and cryopreserved “septal myocardial tissue.” They also reported intact endothelium without blood group antigen expression on freshly harvested human cardiac valve leaflets and no blood group antigen expression nor intact endothelium on cryopreserved valve leaflets. In addition, we found no report in the literature detailing the expression of blood group antigens on homograft conduit (vessel) microvasculature. Thus, our findings of blood group A and B antigen expression and preservation of cryopreserved homograft conduit microvasculature (vasa vasorum) endothelium are indeed unique. We do agree with Dr Jacobs, who wrote the invited comment on our article [5], and with Drs Northrup and Goldstein that an optimal tissue-based implant would lack immunogenicity. Putting aside the issue of whether an immune response to blood group and/or major histocompatibility complex antigens expressed on the homograft microvasculature affects homograft longevity, a significant proportion of children with homograft exposure ultimately require heart transplantation. Many are highly allosensitized, which poses a significant barrier to transplantation [6 – 8]. This problem is likely to grow during the next 10 to 20 years as the initial waves of patients who have been surgical successes in staged single-ventricle palliation reach adolescence or young adulthood and present with end-stage ventricular dysfunction. Although data showing decreased antigen expression on and low panel reactive antibody response to decellularized homografts are encouraging [9], analysis with modern, highly sensitive alloantibody detection techniques (eg, Luminex; Luminex Corp, Austin, TX) would be most indicative of whether or not decellularized homograft is immunogenic. Brian Feingold, MD, MS Peter D. Wearden, MD, PhD Victor O. Morell, MD Daniel Galvis, BS, Pa (Ascp) Csaba Galambos, MD, PhD Children’s Hospital of Pittsburgh of UPMC University of Pittsburgh Medical Center 4401 Penn Ave Pittsburgh, PA 15224 e-mail: [email protected] Ann Thorac Surg 2010;90:357– 63 • 0003-4975/$36.00 doi:10.1016/j.athoracsur.2009.08.044
MISCELLANEOUS
Potential Benefits of Antigen Reduction in Heart Valve Allografts To the Editor: