HLA-B Matching Prolongs Allograft Survival in Islet Cell Transplantation

Overview

Journal Cell Transplant

Specialties Cell Biology
General Surgery

Date 2023 Aug 1

PMID 37526141

Authors

Joana R N Lemos

David A Baidal

Raffaella Poggioli

Virginia Fuenmayor

Carmen Chavez

Ana Alvarez

Camillo Ricordi

Rodolfo Alejandro

Affiliations

Soon will be listed here.

Abstract

Islet cell transplantation (ITx) is an effective therapeutic approach for selected patients with type 1 diabetes with hypoglycemia unawareness and severe hypoglycemia events. In organ transplantation, human leukocyte antigen (HLA) mismatching between donor and recipient negatively impacts transplant outcomes. We aimed to determine whether HLA matching has an impact on islet allograft survival. Forty-eight patients were followed up after islet transplantation at our institution from 2000 to 2020 in a retrospective cohort. Patients underwent intrahepatic ITx or laparoscopic omental approach. Immunosuppression was dependent upon the protocol. We analyzed HLA data restricted to A, B, and DR loci on allograft survival using survival and subsequent multivariable analyses. Patients were aged 42.8 ± 8.4 years, and 64.3% were female. Diabetes duration was 28.6 ± 11.6 years. Patients matching all three HLA loci presented longer graft survival ( = 0.030). Patients with ≥1 HLA-B matching had longer graft survival compared with zero matching ( = 0.025). The number of HLA-B matching was positively associated with time of graft survival (Spearman's rho = 0.590; = 0.034). Analyses adjusted for confounders showed that ≥1 matching for HLA-B decreased the risk of allograft failure ( = 0.009). Our data suggest that HLA-B matching between recipients and donors improved islet allograft survival. Matching all three HLA loci (A, B, and DR) was also associated with prolonged islet allograft survival. Prospective studies and a larger sample size are warranted to validate our findings.

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References

Mittal S, Page S, Friend P, Sharples E, Fuggle S . De novo donor-specific HLA antibodies: biomarkers of pancreas transplant failure. Am J Transplant. 2014; 14(7):1664-71. DOI: 10.1111/ajt.12750. View

Nejentsev S, Howson J, Walker N, Szeszko J, Field S, Stevens H . Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A. Nature. 2007; 450(7171):887-92. PMC: 2703779. DOI: 10.1038/nature06406. View

Massie A, Leanza J, Fahmy L, Chow E, Desai N, Luo X . A Risk Index for Living Donor Kidney Transplantation. Am J Transplant. 2016; 16(7):2077-84. PMC: 6114098. DOI: 10.1111/ajt.13709. View

Shi X, Lv J, Han W, Zhong X, Xie X, Su B . What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients. BMC Nephrol. 2018; 19(1):116. PMC: 5960106. DOI: 10.1186/s12882-018-0908-3. View

Choo S . The HLA system: genetics, immunology, clinical testing, and clinical implications. Yonsei Med J. 2007; 48(1):11-23. PMC: 2628004. DOI: 10.3349/ymj.2007.48.1.11. View

Nerup J, Platz P, Andersen O, Christy M, LYNGSOE J, Poulsen J . HL-A antigens and diabetes mellitus. Lancet. 1974; 2(7885):864-6. DOI: 10.1016/s0140-6736(74)91201-x. View

Lo A, Stratta R, Alloway R, Hodge E . A multicenter analysis of the significance of HLA matching on outcomes after kidney-pancreas transplantation. Transplant Proc. 2005; 37(2):1289-90. DOI: 10.1016/j.transproceed.2004.12.212. View

Forbes S, Flatt A, Bennett D, Crookston R, Pimkova M, Birtles L . The impact of islet mass, number of transplants, and time between transplants on graft function in a national islet transplant program. Am J Transplant. 2021; 22(1):154-164. PMC: 9292186. DOI: 10.1111/ajt.16785. View

Kot M, Baj-Krzyworzeka M, Szatanek R, Musial-Wysocka A, Suda-Szczurek M, Majka M . The Importance of HLA Assessment in "Off-the-Shelf" Allogeneic Mesenchymal Stem Cells Based-Therapies. Int J Mol Sci. 2019; 20(22). PMC: 6888380. DOI: 10.3390/ijms20225680. View

10.

Gruessner A, Sutherland D, Gruessner R . Matching in pancreas transplantation--a registry analysis. Transplant Proc. 2001; 33(1-2):1665-6. DOI: 10.1016/s0041-1345(00)02633-6. View

11.

Susal C, Opelz G . Impact of HLA matching and HLA antibodies in organ transplantation: a collaborative transplant study view. Methods Mol Biol. 2012; 882:267-77. DOI: 10.1007/978-1-61779-842-9_15. View

12.

Broeders N, Racape J, Hamade A, Massart A, Hoang A, Mikhalski D . A new HLA allocation procedure of kidneys from deceased donors in the current era of immunosuppression. Transplant Proc. 2015; 47(2):267-74. DOI: 10.1016/j.transproceed.2014.12.018. View

13.

Bertuzzi F, De Carlis L, Marazzi M, Rampoldi A, Bonomo M, Antonioli B . Long-term Effect of Islet Transplantation on Glycemic Variability. Cell Transplant. 2018; 27(5):840-846. PMC: 6047271. DOI: 10.1177/0963689718763751. View

14.

Dewar P, Wilkinson R, Elliott R, Ward M, Kerr D, Kenward D . Superiority of B locus matching over other HLA matching in renal graft survival. Br Med J (Clin Res Ed). 1982; 284(6318):779-82. PMC: 1496407. DOI: 10.1136/bmj.284.6318.779. View

15.

Bucin D . Specific immune tolerance related to disparity in MHC class I region. Med Hypotheses. 1995; 44(2):132-6. DOI: 10.1016/0306-9877(95)90086-1. View

16.

Noble J, Valdes A . Genetics of the HLA region in the prediction of type 1 diabetes. Curr Diab Rep. 2011; 11(6):533-42. PMC: 3233362. DOI: 10.1007/s11892-011-0223-x. View

17.

Rudolph E, Dunn T, Mauer D, Noreen H, Sutherland D, Kandaswamy R . HLA-A, -B, -C, -DR, and -DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival. Am J Transplant. 2016; 16(8):2401-12. DOI: 10.1111/ajt.13734. View

18.

Foster E, Bridges N, Feurer I, Eggerman T, Hunsicker L, Alejandro R . Improved Health-Related Quality of Life in a Phase 3 Islet Transplantation Trial in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care. 2018; 41(5):1001-1008. PMC: 5911786. DOI: 10.2337/dc17-1779. View

19.

Chaigne B, Geneugelijk K, Bedat B, Alibashe Ahmed M, Honger G, de Seigneux S . Immunogenicity of Anti-HLA Antibodies in Pancreas and Islet Transplantation. Cell Transplant. 2016; 25(11):2041-2050. DOI: 10.3727/096368916X691673. View

20.

Vantyghem M, Kerr-Conte J, Arnalsteen L, Sergent G, Defrance F, Gmyr V . Primary graft function, metabolic control, and graft survival after islet transplantation. Diabetes Care. 2009; 32(8):1473-8. PMC: 2713623. DOI: 10.2337/dc08-1685. View