Donor-Specific Antibody is Associated with Increased Expression of Rejection Transcripts in Renal Transplant Biopsies Classified As No Rejection

2021 ◽  
pp. ASN.2021040433
Author(s):  
Katelynn Madill-Thomsen ◽  
Georg Boehmig ◽  
Jonathan Bromberg ◽  
Gunilla Einecke ◽  
Farsad Eskandary ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Nk Cell ◽  
Standard Of Care ◽  
Transcript Expression ◽  
Transplant Patients ◽  
Increased Risk ◽  
Kidney Transplant Patients ◽  
The Relationship ◽  
Fold Cross Validation ◽  
Hla Antibody

Background: Donor-specific HLA antibody (DSA) is present in many kidney transplant patients whose biopsies are classified as no-rejection (NR). We explored whether in some NR kidneys DSA has subtle effects that are not currently being recognized. Methods: We used microarrays to examine the relationship between standard-of-care DSA and rejection-related transcript increases in 1679 kidney transplant indication biopsies in the INTERCOMEX study (ClinicalTrials.gov NCT01299168), focusing on biopsies classified as NR by automatically assigned archetypal clustering. DSA testing results were available for 835 NR biopsies and were positive in 271 (32%). Results: DSA-positivity in NR biopsies was associated with mildly increased expression of ABMR-related transcripts, particularly IFNG-inducible and NK cell transcripts. We developed a machine learning DSA probability (DSAProb) classifier based on transcript expression in biopsies from DSA-positive vs. DSA-negative patients, assigning scores using 10-fold cross-validation. This DSAProb classifier was very similar to a previously described "ABMR probability" classifier trained on histologic ABMR in transcript associations and prediction of molecular or histologic ABMR. Plotting the biopsies using Uniform Manifold Approximation and Projection revealed a gradient of increasing molecular ABMR-like transcript expression in NR biopsies, associated with increased DSA (P<2E-16). In biopsies with no molecular or histologic rejection, increased DSAProb or ABMR probability scores were associated with increased risk of kidney failure over three years. Conclusions: Many biopsies currently considered to have no molecular or histologic rejection have mild increases in expression of ABMR-related transcripts, associated with increasing frequency of DSA. Thus mild molecular ABMR-related pathology is more common than previously realized.

scholarly journals P1756ANTI-ABO ANTIBODY- VERSUS ANTI-HLA ANTIBODY-INDUCED ANTIBODY MEDIATED REJECTION IN ABO-INCOMPATIBLE KIDNEY TRANSPLANT PATIENTS: RELATIVE INCIDENCE AND PHENOTYPE DIFFERENCE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jinmin Kong ◽  
Hyukyong Kwon ◽  
Sung Son ◽  
EUN Whang
Keyword(s):  
Kidney Transplant ◽  
Blood Group ◽  
Relative Frequency ◽  
Response To Treatment ◽  
Clinical Feature ◽  
Antibody Mediated Rejection ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Hla Antibody ◽  
Case Based

Abstract Background and Aims Antibody-mediated rejection(AMR) in ABO incompatible(ABOi) kidney transplant(KT) patients can either be due to donor-specific anti-HLA antibody(DSA) or anti-blood group antibody. The relative frequency and possible phenotype difference of these two types of AMR in ABOi KT patients have not been reported. Method Of 111 ABOi KT patients between 2007 and 2019 in our center, 15(13.5%) patients developed acute AMR diagnosed by indication biopsy. Since there is no histologic distinction between DSA- and anti-ABO-induced AMR, we assumed the causative antibody in each case based on anti-ABO level and DSA, measured in serum collected at the time of AMR. Results Of these 15 cases of acute AMR, 5 were attributable to anti-ABO(ABO-AMR) since anti-ABO titer was higher (≥16) and DSA was undetectable at the time of rejection. Five cases were attributable to DSA(DSA-AMR) since DSA was detectable and anti-ABO was lower during rejection. Another 3 cases with lower anti-ABO titer and undetectable DSA were also assumed to be DSA-induced, since this low level of anti-ABO is unlikely to cause rejection and DSA can be undetectable in DSA-induced AMR by adsorption of Ab on graft, as frequently seen in ABO-compatible patients Two cases with both higher anti-ABO titer and detectable DSA was regarded as undetermined. The onset of acute AMR was within 2 weeks in all cases(median 7.0 days) and comparable between DSA- and ABO-AMR. Initial anti-ABO titer was also not statistically different; median(range) 256(64-4096) in ABO-AMR and 64(16-256) in DSA-AMR. All the 5 patients with ABO-AMR had negative PRA before KT, whereas 5 of 8 patients with DSA-AMR had positive PRA before KT, and two DSA-AMR patients had preformed DSA before KT. There was no difference in peak creatinine and response to treatment. All the AMR were recovered by treatment and no graft was lost to rejection. No patient with ABO-AMR developed chronic AMR whereas one of DSA-AMR patients developed chronic AMR. Conclusion In summary, among 15 cases of acute AMR, 5 were ABO-AMR, 8 were DSA-AMR and 2 were undetermined. There was no difference in clinical feature between DSA- and ABO-AMR. No patient with ABO-AMR developed chronic AMR.

scholarly journals Is delayed graft function associated with ureteral stenosis in the kidney transplant recipient? A case-control study

2019 ◽  
Vol 13 (11) ◽  
Author(s):  
Axel Cayetano-Alcaraz ◽  
Juan Sebastian Rodriguez-Alvarez ◽  
Mario Vilatobá-Chapa ◽  
Josefina Alberú-Gómez ◽  
Bernardo Gabilondo-Pliego ◽  
...  
Keyword(s):  
Risk Factor ◽  
Kidney Transplant ◽  
Kidney Transplant Recipient ◽  
Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Increased Risk ◽  
Kidney Transplant Patients ◽  
Control Study

Introduction: Ureteral stricture (US) in the kidney transplant recipient is a rare complication that can lead to morbidity and graft loss. Risk factor recognition is crucial in the prevention and management of this entity. Delayed graft function (DGF), as defined by the need for dialysis in the first week after transplantation, has been proposed as a risk factor in previous studies. Our objective is to determine the impact of DGF in US development in kidney transplant patients. Methods: We designed a matched case-control study. US cases in kidney transplant recipients were identified in the 2008–2017 period. We defined US as the rise in serum creatinine associated with findings suggesting obstruction in ultrasound, scintigraphy, or retrograde pyelogram; any other cause of graft dysfunction was excluded. Controls were defined as kidney transplant recipients from the same population and period without US, matched in a 1:2 fashion by age, sex, and donor type. Results: From 532 kidney transplant patients, 31 cases and 62 controls were included. Cumulative US incidence was 58 per 1000 cases. When calculating for odds ratio (OR), post-operative urinoma (OR 3.2; 95% confidence interval [CI] 2.36–4.37) and ureteral duplication (OR 3.29; 95% CI 2.40–4.51) were associated with an increased risk for US, while DGF was not found to be statistically significant as a risk factor (OR 3.3; 95% CI 0.96–11.52). No statistically significant differences were found between groups in other pre- and post-transplant-related factors. Conclusions: DGF was not associated with US in our cohort; however, ureteral duplication and postoperative urinoma were associated with an increased risk of graft ureteral stenosis development.

The complement interference phenomenon as a cause for sharp fluctuations of serum anti-HLA antibody strength in kidney transplant patients

2013 ◽  
Vol 29 (1-4) ◽  
pp. 17-21 ◽  
Author(s):  
Gwendaline Guidicelli ◽  
Guerric Anies ◽  
Thomas Bachelet ◽  
Valérie Dubois ◽  
Jean-François Moreau ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Interference Phenomenon ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Hla Antibody

scholarly journals Association of miRNA146a G>C and miRNA196a-2 C>T Gene Polymorphisms with Outcome of Kidney Transplantation in Iranian Patients

2020 ◽  
Author(s):  
Anahita Abbasi ◽  
Padideh Ebadi ◽  
Ramin Yaghobi ◽  
Mohammad Hossein Karimi
Keyword(s):  
Kidney Transplant ◽  
Gene Polymorphisms ◽  
Transplant Rejection ◽  
Tissue Samples ◽  
Control Of Gene Expression ◽  
Organ Rejection ◽  
Transplant Patients ◽  
Increased Risk ◽  
Kidney Transplant Patients ◽  
Iranian Patients

Acute organ rejection remains a serious clinical challenge. Novel accessible biomarkers of acute rejection could easily enable us to detect the rejection earlier and make more fine-tuned calibration of immunosuppressive or new target treatment possible. Control of gene expression by microRNAs influences many cellular functions, including cellular differentiation, cell proliferation, cell development, and functional regulation of the immune system. Therefore, this study was aimed to investigate if miRNA146a G>C and miRNA196a-2 C>T gene polymorphisms are associated with kidney transplant rejection in Iranian patients. Tissue samples were collected from 100 renal transplant patients between the years 2009 and 2013. The miRNA146a G>C (rs2910164) and miRNA196a-2 C>T (rs11614913) gene polymorphisms were evaluated in kidney transplant patients; using the in-house-polymerase chain Reaction-restriction fragment length polymorphism (PCR-RFLP) method. In this study, we found that the CC genotype, C and G alleles of the miRNA146a G>C polymorphism was associated with increased risk of transplant rejection in kidney transplant patients (p=0.003, p=0.01 and p=0.01), respectively. The CC genotype, T, and C alleles of the miRNA196a-2 C>T were also significantly more frequent in transplanted patients compared to healthy controls (p=0.02, p=0.05, and p=0.05), respectively. However, significant associations were not found between miRNA196a-2 C>T polymorphisms and kidney transplant rejection. The CC genotype, G, and C allele of the miRNA146a G>C and also, the CC genotype, T and C alleles of the miRNA196a-2 C>T may be genetically susceptible factors for transplant rejection and development of kidney disorders, especially in Iranian patients. Further studies are required to validate these findings in a larger population, as well as in patients with different ethnic origins.

scholarly journals Levels of Indoxyl Sulfate in Kidney Transplant Patients, and the Relationship With Hard Outcomes

2016 ◽  
Vol 80 (3) ◽  
pp. 722-730 ◽  
Author(s):  
Sophie Liabeuf ◽  
Lucie Desjardins ◽  
Ziad A. Massy ◽  
François Brazier ◽  
Pierre François Westeel ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Indoxyl Sulfate ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
The Relationship
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