Antibody-mediated Rejection In Kidney Transplantation Research Articles

Targeting CD38 in Subclinical Antibody-mediated Rejection in HLA-incompatible Kidney Transplantation: A Case Report.

Targeting CD38 in Subclinical Antibody-mediated Rejection in HLA-incompatible Kidney Transplantation: A Case Report.

Systematic biopsy-based transcriptomics and diagnosis of antibody-mediated kidney transplant rejection in clinical practice.

To diagnose kidney transplant antibody-mediated rejection, biopsy-based transcriptomics can substitute for some histological criteria according to the Banff classification. However, clinical accessibility of these assays is still limited. Here, we aimed to evaluate the impact of integrating a routine-compatible molecular assay for the diagnosis of antibody-mediated rejection in clinical practice. All biopsies performed in our center between 2013 and 2017 were retrospectively included. These biopsies were classified into three groups: "Antibody-mediated rejection biopsies" which displayed the full Banff criteria of antibody-mediated rejection independently of biopsy-based transcriptomics; "Undetermined for antibody-mediated rejection" biopsies which did not meet antibody-mediated rejection histological criteria, but would have been considered as antibody-mediated rejection if biopsy-based transcriptomics had been positive; and control biopsies which showed no features of rejection. Within the inclusion period, 342 biopsies had a complete Banff scoring. Thirty-six of the biopsies already met antibody-mediated rejection criteria, and 43 out of 306 (14%) were considered as "undetermined for antibody-mediated rejection." Among these biopsies, 24 out of 43 (56%) had a molecular signature of antibody-mediated rejection, reclassifying them into the "antibody-mediated rejection" category. Five-year death-censored survival of these biopsies was unfavorable and statistically equivalent to that of the "antibody-mediated rejection" category (p = 0.22), with 15 out of 24 (63%) graft loss. A significant proportion of biopsies could benefit from a biopsy-based transcriptomics for antibody-mediated rejection diagnosis according to the Banff classification. Using a routine-compatible molecular tool, more than the half of these biopsies were reclassified as antibody-mediated rejection and associated with poor allograft survival.

#1714 The treatment of antibody-mediated rejection in kidney transplantation with recent drugs: a network meta-analysis

Abstract Background and Aims The recent treatments for antibody-mediated rejection (AMR) have been carried out in a small number of controlled clinical trials and are based on limited data. In recent research on AMR treatment, new drugs targeting B cells, plasma cells, the complement system, and IL-6 have been gaining attention. Method Studies on antibody mediated rejection (AMR) treatment were divided into four groups:, 1) rituximab, 2 bortezomib, 3 eculizumab, and 4) tocilizumab. We searched the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2023.5. We performed direct and indirect network meta-analyses using Bayesian models and ranked different AMR treatment method using a generation mixed treatment comparison (GeMTC) and Stata version 13. The outcomes included patient survival, graft failure, and bacterial and viral infections Results This analysis included 21 clinical trials with a total of 1217 participants. We focused on graft failure events based on the use of four groups of medications when patients received induction therapy for AMR treatment. There was a lower tendency in graft failure rates in the bortezomib and tocilizumab groups (odds ratio [OR] 0.31, 95% CrI: 0.058-1.4 and OR 0.42, 95% CrI 0.012-7.4), while the eculizumab group showed a higher graft failure rate (OR 2.3, 95% CrI 0.26-31.0) compared to the rituximab using group. However, these study results were not statistically significant. Conclusion When looking at the study results, although not statistically significant, it was observed that bortezomib and tocilizumab, compared to rituximab, showed a tendency to reduce the incidence of graft failure after AMR occurrence. Although this study did not demonstrate statistical significance, it is believed that future research with increased enrollment and additional studies may help identify effective drugs for AMR treatment.

WCN24-2068 The Effect of Induction Therapy on Antibody-Mediated Rejection in Kidney Transplantation: A Network Meta-Analysis Using Recent Data

WCN24-2068 The Effect of Induction Therapy on Antibody-Mediated Rejection in Kidney Transplantation: A Network Meta-Analysis Using Recent Data

The Effect of Induction Therapy on Antibody-Mediated Rejection in Kidney Transplantation: A Network Meta-Analysis Using Recent Data

Various induction regimens are available for kidney transplantation (KT); however, which is superior remains unclear. Moreover, although the induction regimens are effective and important for reducing side effects, their respective relationships with antibody-mediated rejection (AMR) after transplantation remain unclear. Therefore, this study aimed to elucidate the most effective induction regimen for AMR reduction through network analysis. We performed a comprehensive search of databases, including basiliximab, alemtuzumab, antithymocyte globulin (ATG), and daclizumab as induction regimens for KT from inception to September 1, 2022. Using a network meta-analysis, we investigated the priorities of 5 induction regimens for patient survival, graft failure, and graft rejection after ABO-incompatible KT. In total, 25 studies comprising 1768 people were included in this network meta-analysis. The primary outcome was the AMR rate of other induction regimens compared with that of basiliximab, whereas the secondary outcomes were heart failure, stroke, hospitalization, peripheral artery disease, myocardial infarction, anemia, leukopenia, herpes zoster, or adverse events. Notably, ATG reduced the AMR rate by 59% (odds ratio, 0.41; 95% credible interval, 0.20-0.90), whereas the other drugs did not show statistical significance. Furthermore, secondary outcomes did not significantly differ between the induction regimens. ATG is widely used in KT induction regimens. Our results showed that ATG reduced the risk of AMR in KT recipients when compared with other induction drugs; therefore, it appears to be an efficient choice of induction regimen to reduce AMR after KT.

Impact of Preformed Donor-Specific Anti-HLA-Cw and Anti-HLA-DP Antibodies on Acute Antibody-Mediated Rejection in Kidney Transplantation.

Given the risk of rejection, the presence of preformed donor specific antibodies (DSA) contraindicates transplantation in most allocation systems. However, HLA-Cw and -DP DSA escape this censorship. We performed a multicentric observational study, in which the objective was to determinate risk factors of acute antibody-mediated rejection (aABMR) in recipients transplanted with preformed isolated Cw- or DP-DSA. Between 2010 and 2019, 183 patients were transplanted with a preformed isolated Cw- or DP-DSA (92 Cw-DSA; 91 DP-DSA). At 2years, the incidence of aABMR was 12% in the Cw-DSA group, versus 28% in the DP-DSA group. Using multivariable Cox regression model, the presence of a preformed DP-DSA was associated with an increased risk of aABMR (HR = 2.32 [1.21-4.45 (p = 0.001)]) compared with Cw-DSA. We also observed a significant association between the DSA's MFI on the day of transplant and the risk of aABMR (HR = 1.09 [1.08-1.18], p = 0.032), whatever the DSA was. Interaction term analysis found an increased risk of aABMR in the DP-DSA group compared with Cw-DSA, but only for MFI below 3,000. These results may plead for taking these antibodies into account in the allocation algorithms, in the same way as other DSA.

P230 Donor-specific HLA antibody characteristics at the time of biopsy with and without antibody-mediated rejection in kidney transplantation

P230 Donor-specific HLA antibody characteristics at the time of biopsy with and without antibody-mediated rejection in kidney transplantation

A bibliometric and knowledge-map analysis of antibody-mediated rejection in kidney transplantation

Objectives Antibody-mediated rejection (AMR) is a large obstacle to the long-term survival of allograft kidneys. It is urgent to find novel strategies for its prevention and treatment. Bibliometric analysis is helpful in understanding the directions of one field. Hence, this study aims to analyze the state and emerging trends of AMR in kidney transplantation. Methods Literature on AMR in kidney transplantation from 1999 to 2022 was collected from the Web of Science Core Collection. HistCite (version 12.03.17), CiteSpace (version 6.2.R2), Bibliometrix 4.1.0 Package from R language, and Gephi (https://gephi.org) were applied to the bibliometric analysis of the annual publications, leading countries/regions, core journals, references, keywords, and trend topics. Results A total of 2522 articles related to AMR in kidney transplantation were included in the analysis and the annual publications increased year by year. There were 10874 authors from 118 institutions located in 70 countries/regions contributing to AMR studies, and the United States took the leading position in both articles and citation scores. Halloran PF from Canada made the most contribution to AMR in kidney transplantation. The top 3 productive journals, American Journal of Transplantation, Transplantation, and Transplantation Proceedings, were associated with transplantation. Moreover, the recent trend topics mainly focused on transplant outcomes, survival, and clinical research. Conclusions North American and European countries/regions played central roles in AMR of kidney transplantation. Importantly, the prognosis of AMR is the hotspot in the future. Noninvasive strategies like plasma and urine dd-cfDNA may be the most potential direction in the AMR field.

Emerging Therapies for Antibody-Mediated Rejection in Kidney Transplantation.

Despite the advances in immunosuppressive medications, antibody-mediated rejection (AMR) continues to be a major cause of kidney allograft failure and remains a barrier to improving long-term allograft survival. Recently, there have been significant advances in the understanding of the pathophysiological process of AMR, along with the development of new therapeutic options. Additionally, surveillance protocols with donor-derived cell-free DNA and gene profile testing have been established, leading to the early detection of AMR. A multitude of clinical trials are ongoing, opening numerous opportunities for improving outcome in kidney transplant recipients. In this brief review, we discuss the emerging therapies for managing both active and chronic active AMR and highlight the ongoing clinical trials.

Early Antibody-Mediated Kidney Transplant Rejection: A Successful Case Without Donor-Specific Anti-HLA Antibodies

Early Antibody-Mediated Kidney Transplant Rejection: A Successful Case Without Donor-Specific Anti-HLA Antibodies

Impact of ABO incompatibility and early antibody-mediated rejection on chronic antibody-mediated rejection in kidney transplant patients.

Early antibody-mediated rejection has been reported to increase chronic antibody-mediated rejection and decrease graft survival in kidney transplantation. However, the impact of early antibody-mediated rejection in ABO-incompatible kidney transplantation remains unclear. We retrospectively analyzed living-donor kidney transplantation patients from two Korean centers. Patients were categorized based on ABO compatibility and early antibody-mediated rejection within 1 year. The primary outcome was chronic antibody-mediated rejection. The secondary outcomes were production of de novo donor-specific antibody and composite kidney outcome, defined as graft loss or a decline in estimated glomerular filtration rate to below 30mL/min/1.73 m2. A total of 1639 patients were analyzed, including 1292 patients who underwent ABO-compatible kidney transplantation and 347 patients who underwent ABO-incompatible kidney transplantation. ABO-incompatible kidney transplantation had a lower risk of de novo donor-specific antibody production (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.48-0.95) and chronic antibody-mediated rejection (HR 0.33, 95% CI 0.12-0.92) with a comparable risk of the composite kidney outcome (HR 1.06, 95% CI 0.71-1.59) compared to ABO-compatible kidney transplantation. When outcomes of ABO-incompatible kidney transplantation were analyzed according to early antibody-mediated rejection, ABO-incompatible kidney transplantation without antibody-mediated rejection had a lower risk of de novo donor-specific antibody production (HR 0.60, 95% CI 0.41-0.88) and chronic antibody-mediated rejection (HR 0.28, 95% CI 0.09-0.91) than ABO-compatible kidney transplantation without antibody-mediated rejection. However, ABO-incompatible kidney transplantation with antibody-mediated rejection showed a higher risk of de novo donor-specific antibody production and similar risk of chronic antibody-mediated rejection compared to ABO-compatible kidney transplantation without antibody-mediated rejection. ABO-incompatible kidney transplantation showed a lower risk of de novo donor-specific antibody production and chronic antibody-mediated rejection compared to ABO-compatible kidney transplantation; however, early antibody-mediated rejection abrogated these beneficial effects of ABO-incompatible kidney transplantation.

Modulation of Monocyte Response by MicroRNA-15b/106a/374a During Antibody-mediated Rejection in Kidney Transplantation.

Increasing evidence suggest that microRNAs are involved in the physiopathology of acute or chronic renal disease. In kidney transplantation, as key regulators of cellular homeostasis, microRNAs may be involved in the regulation of immune cell function and the allograft response. Here, we investigated the change in circulating microRNA expression profile and their involvement in the profound transcriptional changes associated with antibody-mediated rejection (AMR). Blood samples were collected at the time of the 710 kidney allograft biopsies at 4 European transplant centers. Messenger RNA and microRNA profiling analyses were performed in a discovery-to-validation study within 3 independent cohorts encompassing N = 126, N = 135, and N = 416 patients, respectively. Compared with samples with no AMR, 14 microRNAs were significantly decreased in AMR samples. Among them, expression levels of microRNA-15b, microRNA-106a, and microRNA-374a gradually decreased with the severity of AMR lesions. From their in silico-predicted target genes, a high proportion proved to be significantly upregulated in the paired transcriptomic analysis. Gene ontology analyses of microRNA-15b/-106a/-374a suggested enrichment in myeloid-related pathways, which was further refined by in silico and ex vivo transcriptomic analyses, showing a specific origin from classical CD14 + monocytes. Finally, human CD14 + monocytes were subjected to transduction by antago-microRNAs to mimic AMR pathology. MicroRNA-15b/-106a/-374a impairment resulted in cellular activation with an increased expression of CD69, CRIM1, IPO7, and CAAP1, direct and common targets of the 3 microRNAs. Together, our data provide new insights into circulating microRNAs as markers and key players in AMR, and they suggest monocyte involvement in this process.

Rationale for the IMAGINE study for chronic active antibody-mediated rejection (caAMR) in kidney transplantation

Chronic active antibody-mediated rejection (caAMR) in kidney transplantation is a major cause of late graft loss and despite all efforts to date, there is no proven effective therapy. Indeed, the Transplant Society (TTS) consensus opinion called for a conservative approach optimizing baseline immunosuppression and supportive care focused on blood pressure, blood glucose, and lipid control. This review provides the rationale and early evidence in kidney transplant recipients with caAMR that supported the design of the IMAGINE study whose goal is to evaluate the potential impact of targeting the IL6/IL6R pathway.

Perturbations of the T-cell immune repertoire in kidney transplant rejection.

In this cross-sectional and longitudinal analysis of mapping the T-cell repertoire in kidney transplant recipients, we have investigated and validated T-cell clonality, immune repertoire chronology at rejection, and contemporaneous allograft biopsy quantitative tissue injury, to better understand the pathobiology of acute T-cell fraction, T-cell repertoire and antibody-mediated kidney transplant rejection. To follow the dynamic evolution of T-cell repertoire changes before and after engraftment and during biopsy-confirmed acute rejection, we sequenced 323 peripheral blood samples from 200 unique kidney transplant recipients, with (n=100) and without (n=100) biopsy-confirmed acute rejection. We report that patients who develop acute allograft rejection, have lower (p=0.01) T-cell fraction even before transplantation, followed by its rise after transplantation and at the time of acute rejection accompanied by high TCR repertoire turnover (p=0.004). Acute rejection episodes occurring after the first 6 months post-transplantation, and those with a component of antibody-mediated rejection, had the highest turnover; p=0.0016) of their T-cell repertoire. In conclusion, we validated that detecting repertoire changes in kidney transplantation correlates with post-transplant rejection episodes suggesting that T-cell receptor sequencing may provide recipient pre-transplant and post-transplant predictors of rejection risk.

Anti-interleukin-6 Antibody Clazakizumab in Antibody-mediated Kidney Transplant Rejection: Effect on Donor-derived Cell-free DNA and C-X-C Motif Chemokine Ligand 10.

We report a secondary endpoint analysis of a phase 2 trial of anti-IL-6 antibody clazakizumab in late AMR (ClinicalTrials.gov, NCT03444103). Twenty kidney transplant recipients were randomized to treatment with clazakizumab or placebo over 12 wk (part A), followed by an extension in which all recipients received clazakizumab through week 52 (part B). Biomarkers were evaluated at day 0 and after 12 and 52 wk, respectively. Fractional dd-cfDNA (dd-cfDNA[%]) did not significantly change under clazakizumab, with no differences between study arms (clazakizumab versus placebo) at week 12 (1.65% [median; interquartile range: 0.91%-2.78%] versus 0.97% [0.56%-2.30%]; P = 0.25) and no significant decrease from weeks 12 to 52 (1.15% [0.70%-2.38%] versus 1.0% [0.61%-1.70%]; P = 0.25). Similarly, urine CXCL10 was not different between groups at week 12 (55.7 [41.0-91.4] versus 60.2 [48.8-208.7.0] pg/mg creatinine; P = 0.44) and did not change over part B (CXCL10 [pg/mg creatinine]: from 58 [46.3-93.1] to 67.4 [41.5-132.0] pg/mL creatinine; P = 0.95). Similar results were obtained for serum CXCL10. There was no association between biomarker levels and resolution of molecular and morphologic AMR activity. Our results suggest that IL-6 blockade does not significantly affect levels of dd-cfDNA[%] and CXCL10. Subtle responses to this therapeutic principle may be overlooked by early biomarker surveillance.

WARS1, TYMP and GBP1 display a distinctive microcirculation pattern by immunohistochemistry during antibody-mediated rejection in kidney transplantation

Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Defined by the Banff classification, its gold standard diagnosis remains a challenge, with limited inter-observer reproducibility of the histological scores and efficient immunomarker availability. We performed an immunohistochemical analysis of 3 interferon-related proteins, WARS1, TYMP and GBP1 in a cohort of kidney allograft biopsies including 17 ABMR cases and 37 other common graft injuries. Slides were interpreted, for an ABMR diagnosis, by four blinded nephropathologists and by a deep learning framework using convolutional neural networks. Pathologists identified a distinctive microcirculation staining pattern in ABMR with all three antibodies, displaying promising diagnostic performances and a substantial reproducibility. The deep learning analysis supported the microcirculation staining pattern and achieved similar diagnostic performance from internal validation, with a mean area under the receiver operating characteristic curve of 0.89 (± 0.02) for WARS1, 0.80 (± 0.04) for TYMP and 0.89 (± 0.04) for GBP1. The glomerulitis and peritubular capillaritis scores, the hallmarks of histological ABMR, were the most highly correlated Banff scores with the deep learning output, whatever the C4d status. These novel immunomarkers combined with a CNN framework could help mitigate current challenges in ABMR diagnosis and should be assessed in larger cohorts.

Antibody-Mediated Rejection in Kidney Transplantation: A Retrospective Study on the Impact of Donor-Specific Antibodies and on the Timing of Diagnosis.

Introduction Limitedinformation exists concerning the clinical significance of histologically confirmed antibody-mediated rejection (h-AMR) without detectable circulating donor-specific antibodies (DSA). In this study, we compared the outcomes of patients with h-AMR according toDSAstatus. Methods A total of 80 kidney transplant (KT) recipients who met the 2018 Banff criteria for h-AMR were included. Clinical and immunological characteristics were evaluated, and outcomes were compared according toDSAstatus after kidney biopsy (KB). Results There were 57 patients who had DSA-positive (+) h-AMR and 23 patients who hadDSA-negative (-) h-AMR. Groups had similar baseline characteristics and time between KT and KB. Concerning histopathological diagnoses/Banff scores,DSA+ patients had higher interstitial fibrosis (ci) and tubular atrophy (ct) (ci+ct) scores and lower arterial hyalinosis (ah) scores compared toDSA- patients. Graft survival (GS) was similar for both groups (64% versus 44% at five years and 44% versus 34% at 10 years).Multivariate analysis revealed the time of KB (less than six months after KT or more than six months after KT) to be associated with GS. A stratified analysis was conducted, targetingDSAstatus according to the time of biopsy. For KB performed less than six months after KT, GS was higher forDSA+ patients at 10 years (66% versus 23%). For KB performed more than six months after KT,DSA- patients had higher GS at 10 years (58% versus 9%). Conclusion Both the timing of AMR diagnosis and DSA status had an impact on AMR outcomes. For patients diagnosed with AMR more than six months after transplantation, GS was worst for those in which circulating DSA were identified. Biopsy specimens from DSA- specimens had higher ct-ci and ah scores.

P8.049: Treatment of Chronic Active Antibody-Mediated Kidney Transplant Rejection With Intravenous Immunoglobulin

Background and Aims: Chronic active antibody-mediated rejection (cAAMR) is one of the main causes of late allograft failure after kidney transplantation. Data on the management of chronic active antibody-mediated rejection after kidney transplantation are limited. Intravenous immunoglobulin (IVIg) is one of the treatment options known to have powerful and multiple immunomodulatory effects. High-dose IVIg delivers a lasting immunomodulatory effect on T cells and especially B cells, resulting in changes in the induction of B cell apoptosis and downstream modulation of B cell signaling. Methods: This was a single-center study of kidney transplant recipients (n=10) treated with high-dose intravenous immunoglobulin for biopsy-confirmed cAAMR. IVIg infusions (1 g/kg) were performed every 4 weeks for 6 months. All patients were followed for at least 12 months clinically and by laboratory tests for graft and patient outcomes. Results: Mean age of recruited patients was 47.3 ±12.74 years. Most of them had first kidney transplant. Glomerulonephritis represented the most common cause of end-stage kidney disease. The time frame for cAAMR development was 32 [7;60] month. 2 patients died from coronavirus COVID-19 and 4 (40%) patients started dialysis during the follow-up period. 4 (40%) kidney transplant recipients with functioning grafts had no significant changes in serum creatinine, glomerular filtration rate and proteinuria after treatment. Conclusion: Monotherapy with intravenous immunoglobulin seems not to be an effective treatment strategy for chronic active antibody-mediated rejection of kidney transplant. New therapeutic approaches are needed to improve the outcome of cAAMR.

Posttransplant-Alloantibodies Against MICA Antigens Associated With Decreased Long-Term Allograft Survival of Kidney Transplant Recipients

Previous evidence showed that antibodies against major histocompatibility complex class I-related chain A (MICA) could lead to antibody-mediated rejection in kidney transplantation in case where the patients had no alloantibodies against HLA. However, the effects of posttransplant anti-MICA antibodies on long-term renal allograft survival and function remained unsettled. We tested the posttransplant anti-MICA antibodies in 150 kidney transplant patients. The aim of this study was to compare the long-term graft survival and function between patients who were MICA positive and those who were negative. The posttransplant serum samples from 150 patients receiving kidney transplantation in our center from 2012 to 2013 were tested for MICA antibodies and HLA antibodies by Luminex single antigen array technology. Graft survival and function were followed up for a mean time of 74.2 months. The research was conducted in accordance with the Helsinki Congress and the Declaration of Istanbul. Of the 150 patients, 38 (25.3%) were sensitized against MICA after transplantation. The anti-MICA antibodies-positive (anti-MICA+) group had a worse long-term renal allograft survival than that of anti-MICA-negative (anti-MICA-) group (P = .029), even when stratified by posttransplant HLA sensitization status or donor source. Anti-MICA antibodies also had a detrimental impact on renal allograft function, but only at 1 year posttransplantation (estimated glomerular filtration rates at 1 year: anti-MICA+ 66.6 mL/min/1.73 m2 vs anti-MICA- 78.7 mL/min/1.73 m2; P = .023). Posttransplant anti-MICA antibodies were associated with decreased long-term renal allograft survival and short-term renal allograft function.

The Ratio of CD226 and TIGIT Expression in Tfh and PD-1+ICOS+Tfh Cells Are Potential Biomarkers for Chronic Antibody-Mediated Rejection in Kidney Transplantation.

Kidney transplantation is the ideal treatment for end-stage renal disease (ESRD). Chronic antibody-mediated rejection (CAMR) is the main cause of graft failure. Tfh and B cells are key immune cells that play important roles in CAMR. In this study, the populations of different Tfh cell phenotypes and B cell subsets in CAMR were investigated in a total of 36 patients. Based on Banff-2019, 15 patients were diagnosed with CAMR (CAMR group), 11 recipients were diagnosed with recurrent or de novo IgA nephropathy (IgAN group), and 10 patients displayed stable renal function (stable group). The Tfh and B cell subsets were analyzed by flow cytometry. The percentage and absolute number of PD-1+ICOS+Tfh cells were significantly higher in CAMR (p < 0.05), as was the ratio of CD226+Tfh cells to TIGIT+Tfh cells (p < 0.05). Compared with stable recipients, CAMR patients had lower naïve B cells and higher unswitched memory B cells, which were also significantly related to renal function (p < 0.05). Using the logistic regression model, we concluded that the estimated glomerular filtration rate (eGFR), absolute number of PD-1+ICOS+Tfh cells, and ratio of CD226+Tfh cells to TIGIT+Tfh cells were independent risk factors for CAMR. The combination of eGFR, PD-1+ICOS+Tfh cells, and the ratio of CD226+Tfh cells to TIGIT+Tfh cells showed better diagnostic efficacy for CAMR than each single parameter. The collective findings show that monitoring different Tfh phenotypes and B cell subsets is beneficial to kidney transplant recipients and implicate the combination of eGFR, number of PD-1+ICOS+Tfh cells, and ratio of CD226+Tfh cells to TIGIT+Tfh cells as a biomarker for diagnosing CAMR. The findings may also inform new strategies to identify and treat CAMR.