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HLA antibodies in liver transplantation

HLA antibodies in liver transplantation. Hugo Kaneku, MD Post-Doctoral Research Fellow Department of Surgery Division of Liver and Pancreas Transplantation UCLA. Terasaki Festschrift January 24-26, 2014. HLA Abs in liver transplantation. 1. 12. Gordon RD, et al. Surgery 1986.

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HLA antibodies in liver transplantation

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  1. HLA antibodies inliver transplantation Hugo Kaneku, MD Post-Doctoral Research Fellow Department of Surgery Division of Liver and Pancreas Transplantation UCLA Terasaki Festschrift January 24-26, 2014

  2. HLA Abs in liver transplantation 1 12 Gordon RD, et al. Surgery 1986 Takaya S, et al. Transplantation 1992

  3. HLA Abs in liver transplantation Significant association between post-tx FCXM and acute rejection (100% vs. 17%, p<0.001)

  4. HLA Abs in liver transplantation De novo DSA: 62% in chronic rejection vs. 38% in controls (p=0.04)

  5. De novo DSA in LT • Biorepository and research database of the Simmons Transplant Institute at Baylor (includes all LT since 1985) • We selected only primary adult LT between 2000-2009 • Without preformed DSA

  6. Patient characteristics (n=749) Kaneku, et al. Am J Transp 2013

  7. Incidence of de novo DSA 5% 92% No DSA 8% 95% class II n=749 n=61 Kaneku, et al. Am J Transp 2013

  8. Effect of de novo DSA on survival DSA- (n=688) DSA+ (n=61) Log-rank p=0.005 Kaneku, et al. Am J Transp 2013

  9. Predictors of de novo DSA Kaneku, et al. Am J Transp 2013

  10. IgG3 subclass DSA in LT

  11. IgG3 DSA increases risk of graft loss Single IgG (32) Multiple IgG without IgG3 (7) Multiple IgG with IgG3 (18) p=0.0087 IgG3 HR: 3.4 (p=0.007) Kaneku, et al. Liver Transp 2012

  12. Incidence of de novo IgG3DSA 34% IgG3- 92% No DSA 8% 66% IgG3+ n=749 n=61

  13. Effect of de novo IgG3 DSA on survival DSA- (n=688) IgG3- DSA (n=21) DSA+ (n=61) IgG3+ DSA (n=40) Graft Survival DSA HR: 1.9 (p=0.01) IgG3 DSA HR: 2.2 (p= 0.002) Logrank p=0.005 Logrank p=0.002

  14. Predictors of de novo IgG3 DSA

  15. Conclusions De novo DSA was detected in 8% of liver transplant recipients at 1 year and is most commonly directed against class II HLA, especially HLA-DQ. 1

  16. Conclusions Both, de novo DSA and IgG3 DSA at 1 year decrease survival and are independent predictors of graft loss. 2

  17. Conclusions IgG3 DSA identifies more harmful DSA. Patients with non-IgG3 DSA show the same survival as patients without DSA. 3

  18. Conclusions The best way to avoid de novo DSA formation is to maintain adequate immunosuppression levels with tacrolimus, especially in patients with HLA-DQ mismatches. 4

  19. Acknowledgment • Terasaki Foundation Laboratory, Los Angeles, CA: • Nubia Banuelos, BS • Paul I. Terasaki, PhD • Annette C. & Harold C. Simmons Transplant Institute at Baylor, Dallas, TX: • Jacqueline O’Leary, MD, MPH • Linda Jennings, PhD • Brian Susskind, PhD • Göran Klintmalm, MD, PhD

  20. Thank you

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