Impacts of donor-specific anti-HLA antibodies and antibody-mediated rejection on outcomes after intestinal transplantation in children
Corresponding Author
L.-M. Petit
Unité d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpitaux Universitaires de Genève, Geneve, Switzerland
Correspondence
Laetitia-Marie Petit, Unité d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpitaux Universitaires de Genève, Geneve, Switzerland.
Email: [email protected]
Search for more papers by this authorM. Rabant
Service d'Anatomopathologie, Hôpital Necker Enfants Malades, Paris, France
Search for more papers by this authorD. Canioni
Service d'Anatomopathologie, Hôpital Necker Enfants Malades, Paris, France
Search for more papers by this authorC. Suberbielle-Boissel
Laboratoire d'Histocompatibilité, Hôpital Saint Louis, Paris, France
Search for more papers by this authorO. Goulet
Service d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpital Necker Enfants Malades, Paris, France
Search for more papers by this authorC. Chardot
Service de Chirurgie Viscérale Pédiatrique, Hôpital Necker Enfants Malades, Paris, France
Search for more papers by this authorF. Lacaille
Service d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpital Necker Enfants Malades, Paris, France
Search for more papers by this authorCorresponding Author
L.-M. Petit
Unité d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpitaux Universitaires de Genève, Geneve, Switzerland
Correspondence
Laetitia-Marie Petit, Unité d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpitaux Universitaires de Genève, Geneve, Switzerland.
Email: [email protected]
Search for more papers by this authorM. Rabant
Service d'Anatomopathologie, Hôpital Necker Enfants Malades, Paris, France
Search for more papers by this authorD. Canioni
Service d'Anatomopathologie, Hôpital Necker Enfants Malades, Paris, France
Search for more papers by this authorC. Suberbielle-Boissel
Laboratoire d'Histocompatibilité, Hôpital Saint Louis, Paris, France
Search for more papers by this authorO. Goulet
Service d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpital Necker Enfants Malades, Paris, France
Search for more papers by this authorC. Chardot
Service de Chirurgie Viscérale Pédiatrique, Hôpital Necker Enfants Malades, Paris, France
Search for more papers by this authorF. Lacaille
Service d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpital Necker Enfants Malades, Paris, France
Search for more papers by this authorAbstract
AMR is a risk factor for graft failure after SBTx. We studied impact of DSAs and AMR in 22 children transplanted between 2008 and 2012 (11 isolated SBTx, 10 liver inclusive Tx, and one modified multivisceral Tx). Three patients never developed DSA, but DSAs were found in seven in the pre-Tx period and de novo post-Tx in 19 children. Pathology revealed cellular rejection (15/19), with vascular changes and C4d+. Patients were treated with IV immunoglobulins, plasmapheresis, and steroids. Rescue therapy included antithymocyte globulins, rituximab, eculizumab, and bortezomib. Pathology and graft function normalized in 13 patients, graft loss occurred in two, and death in seven. At the end of the follow-up, 15 children were alive (68%), 13 with functioning graft (59%). Prognosis factors for poor outcome after Tx were the presence of symptoms at AMR suspicion (P +.033). DSAs were often found following SBTx, mostly de novo. Resistant ACR or severe AMR is still difficult to differentiate, with a high need for immunosuppression in both. DSAs may precede development of severe disease and pathology features on the graft: relationship and correlation need to be better investigated with larger groups before and after Tx.
References
- 1www.intestinaltransplantregistry.org.
- 2Abu-Elmagd KM, Wu G, Costa G, et al. Preformed and de novo donor specific antibodies in visceral transplantation: long-term outcome with special reference to the liver. Am J Transplant. 2012; 12: 3047–3060.
- 3Farmer DG, Venick RS, Colangelo J, et al. Pretransplant predictors of survival after intestinal transplantation: analysis of a single-center experience of more than 100 transplants. Transplantation. 2010; 90: 1574–1580.
- 4Kubal CA, Mangus RS, Vianna RM, et al. Impact of positive flow cytometry crossmatch on outcomes of intestinal/multivisceral transplantation: role of anti-IL2-receptor antibody. Transplantation. 2013; 95: 1160–1166.
- 5Tsai HL, Island ER, Chang JW, et al. Association between donor specific antibodies and acute rejection and resolution in small bowel and multivisceral transplantation. Transplantation. 2011; 92: 709–715.
- 6Dick AAS, Horslen S. Antibody mediated rejection after intestinal transplantation. Review. Curr Opin Organ Transplant. 2012; 17: 250–257.
- 7Monteverde ML, Chaparro A, Goldberg J, et al. Donor-specific anti-HLA antibodies in pediatric renal transplant recipients with creeping creatinine: prevalence, histological correlations, and impact on patient and graft survival. Pediatr Transplant. 2015; 19: 684–690.
- 8Tran A, Fixler D, Huang R, Meza T, Lacelle C, Das BB. Donor-specific HLA alloantibodies: impact on cardiac allograft vasculopathy, rejection, and survival after pediatric heart transplantation. J Heart Lung Transplant. 2015; 35: 87–91.
- 9Goulet O, Sauvat F, Ruemmele F, et al. Results of the Paris program: ten years of pediatric intestinal transplantation. Transplant Proc. 2005; 37: 1667–1670.
- 10Ruiz P, Bagni A, Brown R, et al. Histological criteria for the identification of acute cellular rejection in human small bowel allografts: results of the pathology workshop at the VIII International Small Bowel Transplant Symposium. Transplant Proc. 2004; 36: 335–337.
- 11Sis B, Jhangri GS, Riopel J, et al. A new diagnostic algorithm for antibody mediated microcirculation inflammation in kidney transplants. Am J Transplant. 2012; 12: 1168–1179.
- 12Berry GJ, Angelini A, Burke MM, et al. The ISHLT working formulation for pathological diagnosis of antibody-mediated rejection in heart transplantation: evolution and current status. J Heart Lung Transplant. 2011; 30: 601–611.
- 13Feucht HE, Felber E, Gokel MJ, et al. Vascular deposition of complement split products in kidney allografts with cell-mediated rejection. Clin Exp Immunol. 1991; 86: 464–470.
- 14De Greef E, Avitzur Y, Grant D, et al. The successful use of infliximab as salvage therapy in pediatric intestinal transplant patients with steroid and thymoglobulin resistant late acute rejection. J Pediatr Gastroenterol Nutr. 2012; 54: 565–567.
- 15Creput C, Durrbach A, Samuel D, et al. Incidence of renal and liver rejection and patient survival rate following combined liver and kidney transplantation. Am J Transplant. 2003; 3: 348–356.
- 16Gerlach UA, Lachmann N, Sawitzki B, et al. Clinical relevance of the de novo production of anti-HLA antibodies following intestinal and multivisceral transplantation. Transpl Int. 2014; 27: 280–289.
- 17Lefaucheur C, Loupy A, Hill GS, et al. Long-term outcome according to levels of preformed donor-specific HLA-antibodies in kidney transplantation. J Am Soc Nephrol. 2010; 21: 1398–1406.
- 18Fromont G, Cerf-Bensussan N, Patey N, et al. Small bowel transplantation in children: an immunohistochemical study of intestinal grafts. Gut. 1995; 37: 783–790.
- 19Haas M, Sis B, Racusen LC, et al. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014; 14: 272–283.
- 20Ruiz P, Garcia M, Pappas P, et al. Mucosal vascular alterations in isolated small bowel allografts: relationship to humoral sensitization. Am J Transplant. 2003; 3: 43–49.
- 21Ruiz P, Takahashi H, Delacruz V, et al. International grading scheme for acute cellular rejection in small bowel transplantation: single-center experience. Transplant Proc. 2010; 42: 47–53.
- 22de Serre NP, Canioni D, Lacaille F, et al. Evaluation of c4d deposition and circulating antibody in small bowel transplantation. Am J Transplant. 2008; 8: 1290–1296.
- 23Kaneku H, Wozniak LJ. Donor-specific human leukocyte antigen antibodies in intestinal transplantation. Review. Curr Opin Organ Transplant. 2014; 19: 261–266.
- 24Asaoka T, Sotolongo B, Island ER, et al. MicroRNA signature of acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies. Am J Transplant. 2012; 12: 465–468.
- 25Gonzalez-Roncero F, Suner M, Bernal G, Cabello V, Toro M, Pereira P. Angel Gentil M. Eculizumab treatment of acute antibody mediated rejection in renal transplantation: case reports. Transplant Proc. 2012; 44: 2690–2694.
- 26Tzvetanov I, Spaggiari M, Joseph J, Jeon H, Oberholzer J, Benedetti E. The use of bortezomib as a rescue treatment for acute antibody mediated rejection: report of three cases and review of literature. Transplant Proc. 2012; 44: 2971–2975.
- 27Woddle ES, Walsh RC, Alloway RR, Girnita A, Brailey P. Proteasome inhibitor therapy for antibody mediated rejection. Pediatr Transplant. 2011; 15: 548–556.
- 28Vo AA, Petrozzino J, Yeung K, et al. Efficacy, outcomes, and cost-effectiveness of desensitization using IV IG and rituximab. Transplantation. 2013; 95: 852–858.
- 29Gondolesi G, Blondeau B, Maurette R, et al. Pretransplant immunomodulation of highly sensitized small bowel transplant candidates with intravenous immune globulin. Transplantation. 2006; 81: 1743–1746.