Impact of IgG3 Subclass and C1q-Fixing Donor-Specific HLA Alloantibodies on Rejection and Survival in Liver Transplantation

O’Leary, Jacqueline G.; Kaneku, Hugo; Banuelos, Nubia; Jennings, Linda W.; Klintmalm, Göran B.; Terasaki, Paul I.

doi:10.1111/ajt.13153

Cited by 134 publications

(137 citation statements)

References 46 publications

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“…Consequently, it is reasonable to hypothesize that, given the nature of the procedure, DDLT recipients may be more sensitive to the detrimental effects of HLA antibodies in comparison to LDLT recipients. That said, similar to recent reports, DSA is likely to have an impact in both donor settings because our multivariate analysis demonstrated an independent association between DSA and graft failure regardless of donor type (5)(6)(7)(8)10,(19)(20)(21).…”

Section: Discussionsupporting

confidence: 91%

“…Although early studies suggested correlations between positive crossmatches and graft loss in LT, liver recipients have been routinely transplanted without regard for HLA antibodies for years (1,25). Not until the recent seminal work of multiple investigators has the interest in alloantibodies in LT become reinvigorated (6,7,10,20,26,27). Significant associations have been made between preformed and de novo DSA and liver transplant rejection, alloimmune hepatitis and patient and graft survival (4)(5)(6)(7)(8)(9)(10)19,21,26).…”

Section: Discussionmentioning

confidence: 99%

“…Although older studies did not find a correlation between graft survival and DSA (1-3), more recent data using advanced techniques such as solid-phase antibody testing have found new associations between DSA with high mean fluorescent intensity (MFI) and rejection, alloimmune hepatitis and long-term patient and graft survival (4)(5)(6)(7)(8)(9)(10). Most of the studies, however, have been single center and retrospective in nature.…”

Section: Introductionmentioning

confidence: 99%

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Donor-Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients

Levitsky

Kaneku

Jie

et al. 2016

American Journal of Transplantation

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With less ischemia, improved donor selection and controlled procedures, living donor liver transplantation (LDLT) might lead to less HLA donor-specific antibody (DSA) formation or fewer adverse outcomes than deceased donor liver transplantation (DDLT). Using the multicenter A2ALL (Adult-to-Adult Living Donor Liver Transplantation Cohort Study) biorepository, we compared the incidence and outcomes of preformed and de novo DSAs between LDLT and DDLT. In total, 129 LDLT and 66 DDLT recipients were identified as having serial samples. The prevalence of preformed and de novo DSAs was not different between DDLT and LDLT recipients (p = 0.93). There was no association between patient survival and the timing (preformed vs. de novo), class (I vs. II) and relative levels of DSA between the groups; however, preformed DSA was associated with higher graft failure only in DDLT recipients (p = 0.01). De novo DSA was associated with graft failure regardless of liver transplant type (p = 0.005) but with rejection only in DDLT (p = 0.0001). On multivariate analysis, DSA was an independent risk factor for graft failure regardless of liver transplant type (p = 0.017, preformed; p = 0.002, de novo). In conclusion, although similar in prevalence, DSA may have more impact in DDLT than LDLT recipients. Although our findings need further validation, future research should more robustly test the effect of donor type and strategies to mitigate the impact of DSA.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Donor-Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients

Levitsky

Kaneku

Jie

et al. 2016

American Journal of Transplantation

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“…4,105,107,108,118 IgG3 subclass testing versus standard DSA testing better predicted the risk for death in a large, single-center, retrospective analysis of preformed and de novo DSA. 119 Further supporting this concept, in a pediatric weaning trial, some of the 12 tolerant patients had DSA but none had IgG3 DSA. 120,121 In addition, the presence of an HLA and a non-HLA DSA may increase the risk for fibrosis progression.…”

Section: Donor-specific Alloantibodies In Liver Transplantationmentioning

confidence: 91%

Advancing Transplantation

et al. 2017

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“…39 In an update, presence of IgG3 antibodies, antibody-fixing complement (C1q) and de novo DSAs with MFI greater than 5000 were found to be associated with an increased risk of mortality. 285 Long-term data on the prevalence of de novo DSAs postliver transplant are scarce. In a cross-sectional study of patients with and without histologically proven chronic rejection (n = 39 each), de novo DSAs were observed in 62% of patients with chronic rejection versus 38% without rejection (P = 0.047).…”

Section: Prevalence and Impact Of De Novo Dsas On Graft Function And mentioning

confidence: 99%

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients

et al. 2017

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Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of recipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient modifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes. COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across Europe. The group's remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant. The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting. 12 Department of Gastroenterology and Hepatology, Erasmus MC, University Hospital Rotterdam, the Netherlands. 13 Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Belgium.14 Abdominal Transplant Surgery, Microbiology and Immunology Department, University Hospitals KU Leuven, Belgium. 15 Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Spain. www.transplantjournal.com S1 S olid organ transplantation has evolved from an experimental procedure to an established treatment option for many types of end-stage organ failure. Both patient and graft outcomes are continuing to improve, and 1-year patient and graft survival currently exceed 80%.1,2 However, survival rates gradually decline over the long term. In kidney transplant, 5-and 10-year graft survival rates in Europe are 77% and 56%, and for liver transplant, 64% and 54% (Figures 1 and 2). 3,4 Although most European countries have seen an increase in both living and deceased donation, transplantation is not available to all who would benefit from the procedure, and there is considerable morbidity and mortality for those listed for transplant.6 Therefore, maximizing long-term graft survival and reducing the need for retransplantation is paramount, not only in improving outcomes for the recipients but also for those awaiting a graft. The improvement in outcomes is predominantly due to reduction in (Transplantation. 2017;101:S1-S41). The authors were approached by Astellas to discuss the practical implementation o...

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Impact of IgG3 Subclass and C1q-Fixing Donor-Specific HLA Alloantibodies on Rejection and Survival in Liver Transplantation

Cited by 134 publications

References 46 publications

Donor-Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients

Donor-Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients

Advancing Transplantation

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients

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