Six-year experience with treatment of early donor-specific anti-HLA antibodies in pediatric lung transplantation using a human immunoglobulin-based protocol.
early anti-HLA donor-specific antibodies
human intravenous immunoglobulins
pediatric lung transplantation
treatment
Journal
Pediatric pulmonology
ISSN: 1099-0496
Titre abrégé: Pediatr Pulmonol
Pays: United States
ID NLM: 8510590
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
31
05
2019
accepted:
27
12
2019
pubmed:
8
1
2020
medline:
25
9
2020
entrez:
8
1
2020
Statut:
ppublish
Résumé
Experience with the treatment of early donor-specific anti-HLA antibodies (eDSA) after lung transplantation in children is very limited. At our institution, we have treated patients with eDSA since 2013 with successive infusions of intravenous human immunoglobulins (IVIG), combined in some cases with a single dose of Rituximab and plasmapheresis (therapeutic plasma exchange [tPE]) or immunoabsorption. The aim of this study was to present the 6-year results of IVIG-based therapy in pediatric lung recipients. Records of pediatric (<18 years old) patients transplanted at our institution between 01/2013 and 03/2019 were reviewed. Outcomes were compared between patients with eDSA treated with IVIG (IVIG group) and without eDSA (control group). Median (interquartile range [IQR]) follow-up amounted to 28 (12-52) months. During the study period, 66 lung-transplanted pediatric patients were included, of which 27 (41%) formed the IVIG group and 38 (57%) the control group. Among the IVIG patients, 14 (52%) patients showed concomitant graft dysfunction (possible clinical antibody-mediated rejection). The median time to eDSA detection was 24 (14-63) days after transplantation. eDSA were cleared in 25 (96%) of the 26 patients which completed treatment. At 3 years, graft survival (%) was 73 vs 85 (P = .65); freedom (%) from chronic lung allograft rejection (CLAD) was 89 vs 78 (P = .82); and from infection 47 vs 31 (P = .15), in IVIG vs control patients, respectively. After lung transplantation, an IVIG-based treatment for eDSA yielded high eDSA clearance. IVIG and control patients showed similar CLAD-free and graft survival.
Substances chimiques
Antibodies
0
HLA Antigens
0
Immunoglobulins, Intravenous
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
754-764Informations de copyright
© 2020 The Authors. Pediatric Pulmonology published by Wiley Periodicals, Inc.
Références
Smith JD, Ibrahim MW, Newell H, et al. Pre-transplant donor HLA-specific antibodies: characteristics causing detrimental effects on survival after lung transplantation. J Heart Lung Transplant. 2014;33:1074-1082.
Ius F, Sommer W, Tudorache I, et al. Early-donor-specific antibodies in lung transplantation: risk factors and impact on survival. J Heart Lung Transplant. 2014;33:1255-1263.
Safavi S, Robinson DR, Soresi S, Carby M, Smith JD. De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant. 2014;33:1273-1281.
R. Morrell M, Pilewski JM, Gries CJ, et al. De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation. J Heart Lung Transplant. 2014;33:1288-1294.
Roux A, Bendib Le Lan I, Holifanjaniaina S, et al. Antibody-mediated rejection in lung transplantation: clinical outcomes and donor-specific antibody characteristics. Am J Transplant. 2016;16:1216-1228.
Le Pavec J, Suberbielle C, Lamrani L, et al. De-novo donor-specific anti-HLA antibodies 30 days after lung transplantation are associated with worse outcomes. J Heart Lung Transplant. 2016;35:1067-1077.
Tikkanen JM, Singer LG, Kim SJ, et al. De novo DQ donor-specific antibodies are associated with chronic lung allograft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2016;194:596-606.
Levine DJ, Glanville AR, Aboyoun C, et al. Antibody-mediated rejection of the lung: a consensus report of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2016;35:397-406.
Verleden SE, Vanaudenaerde BM, Emonds MP, et al. Donor-specific and -nonspecific HLA antibodies and outcome post lung transplantation. Eur Respir J. 2017;50(5):1701248. https://doi.org/10.1183/13993003.01248-2017
Hachem RR, Kamoun M, Budev MM, et al. Human Leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study. Am J Transplant. 2018;37:1119-1130.
Tambur AR, Campbell P, Claas FH, et al. Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report. Am J Transplant. 2018;18(7):1604-1614.
Hachem RR, Yusen RD, Meyers BF, et al. Anti-HLA antibodies and preemptive antibody-directed therapy after lung transplantation. J Heart Lung Transplant. 2010;29:973-980.
Witt CA, Gaut JP, Yusen RD, et al. Acute antibody-mediated rejection after lung transplantation: a retrospective, single center, case series. J Heart Lung Transplant. 2013;32:1034-1040.
Jackups R Jr., Canter C, Sweet SC, Mohanakumar T, Morris GP. Measurement of donor-specific HLA antibodies following plasma exchange therapy predicts clinical outcome in pediatric heart and lung transplant recipients with antibody-mediated rejection. J Clin Apher. 2013;28:301-308.
Ius F, Sommer W, Tudorache I, et al. Preemptive treatment with therapeutic plasma exchange and rituximab for early donor-specific antibodies after lung transplantation. J Heart Lung Transplant. 2015;34:50-58.
Ius F, Sommer W, Kieneke D, et al. IgM-enriched human intravenous immunoglobulin-based treatment of patients with early donor specific anti-HLA antibodies after lung transplantation. Transplantation. 2016;100:2682-2692.
Islam AK, Sinha N, DeVos JM, et al. Early clearance vs persistence of de novo donor-specific antibodies following lung transplantation. Clin Transplant. 2017;31(8):e13028.
Vacha M, Chery G, Hulbert A, et al. Antibody depletion strategy for the treatment of suspected antibody-mediated rejection in lung transplant recipients: Does it work? Clin Transplant. 2017;31(3):e12886.
Ius F, Verboom M, Sommer W, et al. Preemptive treatment of early donor-specific antibodies with IgA- and IgM-enriched intravenous human immunoglobulins in lung transplantation. Am J Transplant. 2018;18:2295-2304.
Hayes D Jr, Kopp BT, Sheikh SI, et al. Pretransplant panel reactive antibodies and lung transplant outcomes in children. Thorac Cardiovasc Surg. 2017;65:36-42.
Verleden SE, Todd JL, Sato M, et al. Impact of CLAD phenotype on survival after lung re-transplantation: a multicenter study. Am J Transplant. 2015;15:2223-2230.
Walpen AJ, Laumonier T, Aebi C, Mohacsi PJ, Rieben R. Immunoglobulin M-enriched intravenous immunoglobulin inhibits classical pathway complement activation, but not bactericidal activity of human serum. Xenotransplantation. 2004;11:141-148.
Goldfarb SB, Hayes D Jr, Levvey BJ, et al. International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Twenty-First Pediatric Lung and Heart-Lung Transplantation Report - 2018; Focus Theme: Multiorgan Transplantation. J Heart Lung Transplant. 2018;37:1196-1206.
Dipchand AI, Webber S, Mason K, et al. Incidence, characterization, and impact of newly detected donor-specific anti-HLA antibody in the first year after pediatric heart transplantation: a report from the CTOC-04 study. Am J Transplant. 2018;18:2163-2174.
Irving CA, Carter V, Gennery AR, et al. Effect of persistent versus transient donor-specific HLA antibodies on graft outcomes in pediatric cardiac transplantation. J Heart Lung Transplant. 2015;34:1310-1317.
Engen RM, Park GE, Schumacher CS, et al. Donor-specific antibody surveillance and graft outcomes in pediatric kidney transplant recipients. Transplantation. 2018;102:2072-2079.
Brugière O, Roux A, Le Pavec J, et al. Role of C1q-binding anti-HLA antibodies as a predictor of lung allograft outcome. Eur Respir J. 2018;52(2):1701898.
Jordan SC, Toyoda M, Kahwaji J, Vo AA. Clinical aspects of intravenous immunoglobulin use in solid organ transplant recipients. Am J Transplant. 2011;11:196-202.
Tedla FM, Roche-Recinos A, Brar A. Intravenous immunoglobulin in kidney transplantation. Curr Opin Organ Transplant. 2015;20:630-637.
Koenig A, Mariat C, Mousson C, Wood KJ, Rifle G, Thaunat O. B cells and antibodies in transplantation. Transplantation. 2016;100:1460-1464.
Lobo PI. Role of natural autoantibodies and natural IgM anti-leucocyte autoantibodies in health and disease. Front Immunol. 2016;7:198. https://doi.org/10.3389/fimmu.2016.00198
Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity. 2009;30:636-645.
Haynes SE, Saini S, Schowengerdt KO. Post-transplant lymphoproliferative disease and other malignancies after pediatric cardiac transplantation: an evolving landscape. Curr Opin Organ Transplant. 2015;20:562-569.
Van Besien K, Bachier-Rodriguez L, Satlin M, et al. Prophylactic rituximab prevents EBV PTLD in haplo-cord transplant recipients at high risk. Leuk Lymphoma. 2019:1-4. https://doi.org/10.1080/10428194.2018
Delapierre B, Reman O, Dina J, et al. Low dose Rituximab for pre-emptive treatment of Epstein Barr virus reactivation after allogenic hematopoietic stem cell transplantation. Curr Res Transl Med. 2019;67:145-148.