Influence of glutathione S-transferase T1 donor/recipient mismatch and anti-GSTT1 antibodies in hepatic graft-versus-host-disease

Martínez-Bravo, María José; Tallón, Inmaculada; Espigado, Ildefonso; Pérez-Simón, Josè Antonio; Pérez‐Romero, Pilar; Gracia-Ahufinger, Irene; Aguilera, Isabel; Núñez‐Roldán, Antonio

doi:10.1016/j.imlet.2011.09.005

Cited by 8 publications

(3 citation statements)

References 26 publications

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“…We have previously shown that GSTT1 mismatch may elicit a specific antibody response after allogeneic stem cell transplantation in cases where donors were previously primed through pregnancy. Specific anti-GSTT1 antibodies were associated with the development of hepatic acute GVHD [15]. On the other hand, we have demonstrated T cell activation after stimulation with GSTT1 peptides in GSTT1mismatched patients who underwent liver transplantation, Figure 2.…”

Section: Discussionmentioning

confidence: 77%

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Mismatch on Glutathione S-Transferase T1 Increases the Risk of Graft-versus-Host Disease and Mortality after Allogeneic Stem Cell Transplantation

Martínez-Bravo

Calderón-Cabrera

Márquez-Malaver

et al. 2014

Biology of Blood and Marrow Transplantation

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Several drug-metabolizing enzymes, preferentially expressed in the liver, have the potential to act as minor histocompatibility antigens. In the present study, we analyzed the impact of glutathione S-transferase T1 (GSTT1), glutathione S-transferase M1, glutathione S-transferase P1, and UDP glucuronosyl transferase 2B17 (UGT2B17) disparities on the outcome of 125 patients undergoing allogeneic hematopoietic stem cell transplantation. Grades 2 to 4 acute graft-versus-host disease (aGVHD) developed in 56.2% versus 73.3% of GSTT1-matched versus mismatched patients (P = .048). Remarkably, 8.6% GSTT1-matched patients developed grades 2 to 4 liver aGVHD, compared with 36.8% among GSTT1-mismatched recipients (P < .001). Regarding chronic graft-versus-host disease (cGVHD), 34.8% versus 70.7% matched versus mismatched patients developed overall cGVHD (P = .038) and 16.3% versus 48% developed hepatic cGVHD (P = .006). We also found a strong association between the UGT2B17 mismatch and the risk of severe aGVHD (P = .001), especially with gut involvement (P < .001). Most striking was the influence of the GSTT1 mismatch on nonrelapse mortality (26.8% versus 52.6%, P = .031) and overall survival (62% versus 36.9%, P = .045). In summary, UGT2B17 and GSTT1 mismatch are risk factors for the development of GVHD and the latter also influences on mortality and survival after allogeneic transplantation from HLA-identical donors.

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Section: Discussionmentioning

confidence: 77%

“…These Abs constitute a risk factor to develop de novo immune hepatitis [13] or chronic antibody-mediated rejection [14]. In addition, we have previously described that the presence of these Abs may induce hepatic GVHD in GSTT1-positive patients who receive allo-HSCT from GSTT1-null donors [15,16].…”

Section: Introductionmentioning

confidence: 99%

Mismatch on Glutathione S-Transferase T1 Increases the Risk of Graft-versus-Host Disease and Mortality after Allogeneic Stem Cell Transplantation

Martínez-Bravo

Calderón-Cabrera

Márquez-Malaver

et al. 2014

Biology of Blood and Marrow Transplantation

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“…Yeo et al [ 23 ] explored the role of GSTT1 in cardiothoracic transplantation and demonstrated that pre-transplant anti-GSTT1 antibodies that developed post transfusion are associated with a higher incidence of acute allograft rejection. Martinez-Bravo et al [ 24 ] investigated the production of anti-GSTT1 antibodies and their involvement in hepatic Graft-versus-Host Disease (GvHD) post HSCT. Furthermore, GSTT1 donor/recipient mismatches are associated with an increased risk of developing acute and chronic GvHD.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Clinical Relevance of Antibodies against Non-Human Leukocyte Antigen in Kidney Transplantation

Bhutani,

Harris,

Carr

et al. 2024

Antibodies

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Introduction: Kidney transplantation is the preferred modality of kidney replacement therapy for eligible patients with end-stage kidney disease (ESKD), given that it has been found to reduce mortality rates, improve quality of life, and is cost-effective compared to dialysis. Recent advancements in human leukocyte antigen (HLA) typing and donor-specific antibody (DSA) detection have helped to reduce the risk of rejection, but antibody-mediated rejection (AMR) can still occur without DSA. Previous studies suggest that rejection can be attributed to antibodies against Non-Human Leucocyte Antigens (non-HLAs). We aimed to acquire further understanding of the prevalence and distribution of non-HLA antibodies in our local population and attempt to correlate these findings with graft outcomes, as well as assess whether non-HLA antibodies can be utilized to determine graft impairment and dysfunction. Methods: We conducted a retrospective study involving kidney transplant recipients between January 2010 and December 2020. All included individuals were aged over 18 and underwent kidney-alone transplants; were ABO- and HLA-compatible; and were matched at A, B, and DR loci (mismatch 0:0:0). HLA testing was negative at the time of transplantation. The samples from both cases of early graft rejection and the control group were tested for non-HLA antibodies using One Lambda LABScreenTM, Autoantibody kit groups 1, 2, and 3, as well as the Immucor LIFECODES non-HLA autoantibody assay. Results: A total of 850 kidney transplant recipients were included, in which 12 patients experienced early graft rejection within the first month post transplant and 18 patients who did not experience graft rejection were selected as study controls. Our study reported no correlation between the total burden of non-HLA antibodies and early rejection, most likely as the result of a small sample size. Nevertheless, a sub-analysis revealed that specific high-frequency pre-transplant non-HLA antibodies such as GSTT, CXCL11, CXCL10, and HNR, detected by LIFECODES, were associated with rejection (Fisher’s exact test with Bonferroni correction, p < 0.001). Most pre-transplant non-HLA antibody levels were reduced after transplantation, which was attributed to immunosuppression. Conclusion: The ‘high frequency’ non-HLA antibodies displayed an association with graft rejection, though the overall associations between the burden of non-HLA antibodies and rejection episodes remain inconclusive. Further work is needed to establish the rebound phenomenon of non-HLA antibodies, the development of de novo non-HLA antibodies in the long run, and their implications on graft survival.

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Transplantation Pathology

Clouston¹,

Hübscher²

2018

Macsween's Pathology of the Liver

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Influence of glutathione S-transferase T1 donor/recipient mismatch and anti-GSTT1 antibodies in hepatic graft-versus-host-disease

Cited by 8 publications

References 26 publications

Mismatch on Glutathione S-Transferase T1 Increases the Risk of Graft-versus-Host Disease and Mortality after Allogeneic Stem Cell Transplantation

Mismatch on Glutathione S-Transferase T1 Increases the Risk of Graft-versus-Host Disease and Mortality after Allogeneic Stem Cell Transplantation

Evaluating the Clinical Relevance of Antibodies against Non-Human Leukocyte Antigen in Kidney Transplantation

Transplantation Pathology

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