The emerging field of non–human leukocyte antigen antibodies in transplant medicine and beyond

Lefaucheur, Carmen; Louis, Kévin; Philippe, Aurélie; Loupy, Alexandre; Coates, P. Toby

doi:10.1016/j.kint.2021.04.044

Cited by 29 publications

(21 citation statements)

References 124 publications

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“…The deleterious interaction between antibodies and the endothelium has been identified as a major pathomechanism responsible for the acute inflammatory process and chronic progression of vascular lesions in vasculopathic disorders in both autoimmunity and alloimmunity. 1 In transplantation, human leukocyte antigen (HLA) antibodies are well recognized to induce changes in the allograft vasculature resulting in acute antibodymediated rejection and progression to transplant vasculopathy leading to allograft destruction. 2 In contrast, the clinical effects induced by non-HLA antibodies have been much less appreciated and the description of their mechanisms of action on allograft vasculature remains at a preliminary stage.…”

Section: See Basic Research On Page 498mentioning

confidence: 99%

“…Jeffrey D. Pressly 1 , Mengyuan Ge 1 and Alessia Fornoni 1 Lipid dysmetabolism is emerging as an important contributor to diabetic kidney disease, suggesting that intrarenal lipid accumulation is detrimental to kidney function. This commentary discusses the finding by Yoshioka et al, connecting tubular lipotoxicity induced by an increase in locally produced lysophosphatidylcholine in patients with a fast progression of diabetic kidney disease, known as "fast decliner."…”

Section: Lpcing Through the Nephron Accelerates Diabetic Kidney Diseasementioning

confidence: 99%

“…Dysregulation of lipid metabolism contributes to several forms of chronic kidney diseases, including diabetic kidney disease (DKD). 1 Although circulating lipids have been reported to play a role in kidney disease development and progression, the contribution of renal accumulation of lipids and impaired renal lipid metabolism to the progression of DKD has recently gained attention. Excess lipids are stored in lipid droplets (LDs), the lipid-rich intracellular organelles that are composed of triglyceride and cholesterol ester core and are shielded by a phospholipid monolayer and an outer layer of protein.…”

Section: Lpcing Through the Nephron Accelerates Diabetic Kidney Diseasementioning

confidence: 99%

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mTOR signaling cascade: novel clinical implications in HLA and non-HLA antibody-mediated vasculopathies?

Louis

Loupy

Lefaucheur

2022

Kidney International

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Section: See Basic Research On Page 498mentioning

confidence: 99%

Section: Lpcing Through the Nephron Accelerates Diabetic Kidney Diseasementioning

confidence: 99%

Section: Lpcing Through the Nephron Accelerates Diabetic Kidney Diseasementioning

confidence: 99%

See 1 more Smart Citation

mTOR signaling cascade: novel clinical implications in HLA and non-HLA antibody-mediated vasculopathies?

Louis

Loupy

Lefaucheur

2022

Kidney International

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“…While the number of publications linking non-HLA antibodies to the development of ABMR histology (ABMR h ) is growing, it is still unclear how these non-HLA antibodies contribute to kidney allograft damage and graft failure. Currently, there is inadequate consensus for routine testing of any non-HLA antibody for diagnosing ABMR (8)(9)(10)(11)(12), although there is growing literature on the role of anti-angiotensin receptor II type 1 antibodies as risk factor for ABMR and graft failure and for potential future clinical implementation (13,14).…”

Section: Introductionmentioning

confidence: 99%

The Pre-Transplant Non-HLA Antibody Burden Associates With the Development of Histology of Antibody-Mediated Rejection After Kidney Transplantation

et al. 2022

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BackgroundMany kidney allografts fail due to the occurrence of antibody-mediated rejection (ABMR), related to donor-specific anti-HLA antibodies (HLA-DSA). However, the histology of ABMR can also be observed in patients without HLA-DSA. While some non-HLA antibodies have been related to the histology of ABMR, it is not well known to what extent they contribute to kidney allograft injury. Here we aimed to investigate the role of 82 different non-HLA antibodies in the occurrence of histology of ABMR after kidney transplantation.MethodsWe included all patients who underwent kidney transplantation between 2004-2013 in a single center and had biobanked serum. Pre- and post-transplant sera (n=2870) were retrospectively tested for the presence of 82 different non-HLA antibodies using a prototype bead assay on Luminex (Immucor, Inc). A ratio was calculated between the measured MFI value and the cut-off MFI defined by the vendor for each non-HLA target.Results874 patients had available pretransplant sera and were included in this analysis. Of them, 133 (15.2%) received a repeat kidney allograft, and 100 (11.4%) had pretransplant HLA-DSA. In total, 204 (23.3%) patients developed histology of ABMR after kidney transplantation. In 79 patients (38.7%) the histology of ABMR was explained by pretransplant or de novo HLA-DSA. The multivariable Cox analysis revealed that only the broadly non-HLA sensitized (number of positive non-HLA antibodies) patients and those with the highest total strength of the non-HLA antibodies (total ratios of the positive non-HLA antibodies) were independently associated with increased rates of histology of ABMR after transplantation. Additionally, independent associations were found for antibodies against TUBB (HR=2.40; 95% CI 1.37 – 4.21, p=0.002), Collagen III (HR=1.67; 95% CI 1.08 – 2.58, p=0.02), VCL (HR=2.04; 95% CI 1.12 – 3.71, p=0.02) and STAT6 (HR=1.47; 95% CI 1.01 – 2.15, p=0.04). The overall posttransplant non-HLA autoreactivity was not associated with increased rates of ABMRh.ConclusionsThis study shows that patients highly and broadly sensitized against non-HLA targets are associated with an increased risk of ABMR histology after kidney transplantations in the absence of HLA-DSA. Also, some pretransplant non‐HLA autoantibodies are individually associated with increased rates of ABMR histology. However, whether these associations are clinically relevant and represent causality, warrants further studies.

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“…Several antigens recognized by non-HLA antibodies have been described in the last 15 years [2,3]. Angiotensin II type I receptor antibodies (AT1R-Ab) have generated the most interest in the KT community amongst the non-HLA antibodies [4]. The frequency of AT1R-Ab in KT ranges from 2.1% to 59%, that of preformed AT1R-Ab being identical to the aforementioned range and that of de novo AT1R-Ab varying between 3.8-51.5% [5].…”

Section: Introductionmentioning

confidence: 99%

Immunosuppression as a Risk Factor for De Novo Angiotensin II Type Receptor Antibodies Development after Kidney Transplantation

Sorohan

Sinescu

Tacu

et al. 2021

JCM

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(1) Background: Angiotensin II type I receptor antibodies (AT1R-Ab) represent a topic of interest in kidney transplantation (KT). Data regarding the risk factors associated with de novo AT1R-Ab development are lacking. Our goal was to identify the incidence of de novo AT1R-Ab at 1 year after KT and to evaluate the risk factors associated with their formation. (2) Methods: We conducted a prospective cohort study on 56 adult patients, transplanted between 2018 and 2019. Recipient, donor, transplant, treatment, and complications data were assessed. A threshold of >10 U/mL was used for AT1R-Ab detection. (3) Results: De novo AT1R-Ab were observed in 12 out of 56 KT recipients (21.4%). The median value AT1R-Ab in the study cohort was 8.5 U/mL (inter quartile range: 6.8–10.4) and 15.6 U/mL (10.8–19.8) in the positive group. By multivariate logistic regression analysis, induction immunosuppression with anti-thymocyte globulin (OR = 7.20, 95% CI: 1.30–39.65, p = 0.02), maintenance immunosuppression with immediate-release tacrolimus (OR = 6.20, 95% CI: 1.16–41.51, p = 0.03), and mean tacrolimus trough level (OR = 2.36, 95% CI: 1.14–4.85, p = 0.01) were independent risk factors for de novo AT1R-Ab at 1 year after KT. (4) Conclusions: De novo AT1R-Ab development at 1 year after KT is significantly influenced by the type of induction and maintenance immunosuppression.

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The emerging field of non–human leukocyte antigen antibodies in transplant medicine and beyond

Cited by 29 publications

References 124 publications

mTOR signaling cascade: novel clinical implications in HLA and non-HLA antibody-mediated vasculopathies?

mTOR signaling cascade: novel clinical implications in HLA and non-HLA antibody-mediated vasculopathies?

The Pre-Transplant Non-HLA Antibody Burden Associates With the Development of Histology of Antibody-Mediated Rejection After Kidney Transplantation

Immunosuppression as a Risk Factor for De Novo Angiotensin II Type Receptor Antibodies Development after Kidney Transplantation

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