Rejection Episodes Research Articles

Human leukocyte antigen compatibility and incidence of donor-specific antibodies in pediatric liver transplant recipients.

Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited. To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT. A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of de novo DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex® single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy. Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively. Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.

The role of C4d and donor specific antibodies in face and hand transplantation-a systematic review.

To date, little is known about the mechanisms of rejection in vascularized composite allotransplantation, particularly for antibody mediated rejection. Additionally, no clear guidelines exist for the diagnosis and management of antibody-mediated rejection in vascularized composite allotransplantation. A systematic review of electronic databases (Embase and PubMed) was conducted to evaluate the relationship of donor specific antibodies and C4d deposition in correlation with cellular rejection following hand and face transplantation reported by centers between 1998 and July 2023. We extracted data on serum donor specific antibodies at the time of biopsy proven rejection according to Banff classification and C4d staining of target tissues. Mann-Whitney U tests were performed to compare rejection grade between groups divided by status of C4d deposition and serum donor specific antibodies, and Fisher's Exact test was used to assess association between the two markers. This review adhered to PRISMA guidelines. A total of 26 patients (5 face, 21 hand) were identified and data on 90 acute rejection episodes with information on Banff grade, donor specific antibody status, and C4d deposition were available. Donor specific antibodies were found to be associated with higher rejection grade (p = 0.005). C4d was not found to be associated with higher rejection grade (p = 0.33). Finally, no significant association was found between concurrent status of the two markers (p = 0.23). These findings suggest that the presence of donor specifc antibodies may be associated with higher grades of acute cellular rejection following hand and face transplantation. More consistent reporting on rejection episodes is needed in order to better understand antibody-mediated rejection in vascularized composite allotransplantation.

Evaluation of Virtual Care in Kidney Transplant Recipients in the Early Posttransplant Period.

Though virtual care was widely adopted during the COVID-19 pandemic, evidence to support its use in kidney transplant recipients early after transplantation is limited. We conducted a retrospective cohort study comparing post kidney transplant outcomes in patients who received in-person transplant care before the COVID-19 pandemic with those who received mainly virtual transplant care during the COVID-19 pandemic. The usual-care group included 69 patients who received a kidney transplant from March 1, 2019 to September 1, 2019, and the virtual-care group included 64 patients who received a kidney transplant from September 1, 2020 to March 1, 2021. At 6 months, five patients in the usual-care group and three patients in the virtual-care group died. There was one graft loss and one episode of acute rejection in the usual-care group, and two episodes of acute rejection in the virtual-care group (p = 0.60). Estimated glomerular filtration rate was higher for patients in the virtual-care group (59mL/min/1.73m2 vs. 52mL/min/1.73m2, p = 0.046) and serum creatinine was not different (138 µmol/L vs. 127µmol/L, p = 0.27). There was no difference in mean blood pressure or hospitalizations. Outcomes were similar among recipients of a kidney transplant prior to the COVID-19 pandemic when care was mainly in person and during the pandemic when care was mainly virtual, without a signal of harm. Patient and donor selection may have led to unmeasured differences between groups.

P.272: Four-drug immunosuppressive treatment as rescue therapy in kidney transplant recipients with repeated episodes of acute rejection or chronic allograft rejection.

P.272: Four-drug immunosuppressive treatment as rescue therapy in kidney transplant recipients with repeated episodes of acute rejection or chronic allograft rejection.

Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant Recipients in the CERTAIN Registry

IntroductionData on age-related differences in rejection rates, infectious episodes and tacrolimus exposure in pediatric kidney transplant recipients (pKTR) on a tacrolimus-based immunosuppressive regimen are scarce. MethodsWe performed a large-scale analysis of 802 pKTR from the CERTAIN registry from 40 centers in 14 countries. Inclusion criteria were a tacrolimus-based immunosuppressive regimen and at least two years of follow-up. The patient population was divided into three age groups (infants and young children <6 years, school-aged children 6-12 years, and adolescents >12 years) to assess age-related differences in outcome. ResultsMedian follow-up was 48 months (IQR, 36-72). Within the first 2 years post-transplant, infants and young children had a significantly higher incidence of infections (80.6% vs. 55.0% in adolescents, P<0.001) and a significantly higher number of cumulative hospital days (median 13 days vs. 7 days in adolescents, P < 0.001). Adolescents had a significantly higher rate of biopsy-proven acute rejection episodes in the first year post-transplant (21.7%) than infants and young children (12.6%, P=0.007). Infants and young children had significantly lower tacrolimus trough levels, lower tacrolimus concentration-to-dose ratios as an approximation for higher tacrolimus clearance, and higher tacrolimus intra-patient variability (all P < 0.01) than adolescents. ConclusionsThis largest study to date in European pKTR on a tacrolimus-based immunosuppressive regimen shows important age-related differences in rejection rates, infection episodes, tacrolimus exposure and clearance. These data suggest that immunosuppressive therapy in pKTR should be tailored and personalized according to the age-specific risk profiles of this heterogeneous patient population. The data may also serve as a benchmark for future studies with novel immunosuppressive drugs.

410.1: The effect of steroid pulse therapy for the reduction of acute rejection episode in subclinical borderline changes: An open-label, randomized clinical trial.

410.1: The effect of steroid pulse therapy for the reduction of acute rejection episode in subclinical borderline changes: An open-label, randomized clinical trial.

Comparative Efficacy and Safety of Low-Dose Versus Standard-Dose Rabbit Antithymocyte Globulin Induction Strategy in Kidney Transplant Recipients: Insights From a Single-Center Experience in North India.

Background Rabbit antithymocyte globulin (rATG) is frequently utilized as an induction therapy in kidney transplant recipients (KTRs). Full-dose rATG induction therapy (7-10 mg/kg) has been associated with increased morbidity. However, definitive data on the appropriate rATG dosage remains scarce. In this study, we evaluated the efficacy and tolerability of varying rATG doses in KTRs. Methodology A single-center, retrospective, observational study was conducted between 2009 and 2014 in a cohort of 208 KTRs who received rATG induction therapy. Patients included in the study had received two to three consecutive doses of rATG as part of their planned induction protocol. Participants were categorized into the following two groups based on the cumulative dosage of rATG received during induction therapy: group A received 2 or 2.5 mg/kg, while group B received ≥3 mg/kg. The five-year follow-up data were analyzed. Results A cumulative rATG dose of 2 or 2.5 mg/kg and ≥3 mg/kg was given to 122 and 86 patients, respectively. The incidence of delayed graft function (DGF), acute rejection episodes, total graft loss, death, and death-censored graft loss was 6.25%, 3.84%, 7.21%, 4.32%, and 2.88%, respectively. Two malignancies and 141 infectious complications were noted. There was no significant difference between the groups regarding DGF, total graft loss, death, death-censored graft loss, infectious complications, and incidence of acute rejection episodes. Deceased donor kidney transplantation was identified as a significant predictor of acute rejection episodes (odds ratio = 9.19, 95% confidence interval = 1.567-53.907; p = 0.014). Conclusions The dosage for rATG induction therapy for KTRs should be tailored based on immunological and other factors impacting graft survival, along with a comprehensive risk assessment for potential infectious complications. A cumulative dose of 2.0 or 2.5 mg/kg could be optimal, offering effective induction therapy in KTRs with excellent graft survival rates and potentially fewer infectious complications.

Perspectives of heart xenotransplantation: a quantitative analysis of this treatment in patients with heart disease

The shortage of human donors for heart transplants has driven research into viable alternatives, such as heart xenotransplantation. This study conducted a quantitative analysis of the perspectives of heart xenotransplantation in the treatment of patients with heart disease. The objective was to evaluate clinical efficacy, the immunosuppression techniques used, the results obtained in case studies and meta-analyses, and compare xenotransplantation with allogeneic transplantation methods. The methodology involved a literature review covering the period from 2014 to 2024, using databases such as Scielo, Google Scholar, scientific journals, repositories, and virtual libraries. Initially, 105 studies were found, of which 15 were selected after applying inclusion and exclusion criteria. The results showed that grafts from genetically modified pig hearts can survive for extended periods in non-human primates, with some survivals documented for up to 945 days. Effective immunosuppression techniques, such as CD40-CD154 costimulation blockade and the use of anti-CD20 antibodies, significantly reduced episodes of acute rejection. Practical implications include the potential reduction of waiting time for patients in need of transplants and offering new hope for those with terminal heart failure. However, technical, ethical, and biological challenges still need to be overcome. It is concluded that heart xenotransplantation is a promising field that deserves continuous attention and investment in research to advance towards safe and effective clinical application.

Molecular screening of transitional B cells as a prognostic marker of improved graft outcome and reduced rejection risk in kidney transplant.

Understanding immune cell dynamics in kidney transplantation may provide insight into the mechanisms of rejection and improve patient management. B cells have gained interest with a special relevance of the "regulatory" subsets and their graft outcome prognostic value. In this study, we aimed to prove that the direct immunophenotyping and target gene expression analysis of kidney transplant patients' fresh whole blood will help to identify graft rejection risk and assist in the monitoring of kidney transplanted patients. We employed flow cytometry and qPCR techniques to characterize B and T cell subsets within fresh whole blood samples, with particular emphasis on transitional B cells (TrB) identified as CD19+CD24hiCD38hi. TrB are a relevant population in the context of kidney transplantation and are closely associated with regulatory B cells (Bregs) in humans. Patients were monitored, tracking pertinent clinical parameters and kidney-related events, including alterations in graft function and episodes of biopsy proven rejection. Higher percentages of TrB cells at 3 months after transplantation were positively associated with better graft outcomes and lower biopsy-proven acute rejection risk. Furthermore, a novel panel of B cell regulatory associated genes was validated at 3 months post-transplantation by qPCR analysis of peripheral blood mononuclear cell (PBMC) mRNA, showing high predictive power of graft events and prognostic value. These findings suggest that monitoring TrB may provide interesting patient management information, improve transplant outcomes, and allow for personalized drug regimens to minimize clinical complications.

Advancing Precision in Vascularized Composite Allografts through Multiplex Sensing of Predictive Biomarkers

Vascularized Composite Allotransplantation (VCA) is a promising option for extensive tissue reconstruction. Successful graft outcomes in VCA surgeries require close monitoring of immunological reactions and the progression of ischemic conditions. Excessive immunosuppression may lead to chronic infections and dangerous side effects, while inadequate immunosuppression can result in acute or chronic rejection episodes, jeopardizing graft function. Monitoring the immunological status of an allograft becomes critical when exploring innovative tolerance induction protocols or transitioning patients from conventional therapies. Currently, confirming clinical rejection involves invasive biopsies, which are suboptimal for routine monitoring due to associated risks. Thus, developing non-invasive technologies capable of detecting changes in the immunological status of the graft before apparent clinical signs of inflammation and tissue damage become imperative. To address these limitations, this study proposes a low-cost, portable, flexible, miniaturized, and site-of-care (SOC) platform for multiplex sensing of predictive biomarkers (e.g., interleukin 6 (IL6), lactate) and pH to detect instances of VCA rejection before apparent clinical signs of immunogenic reactions such as inflammation and tissue damage.The sensor fabrication was performed on in-house fabricated porous laser-engraved graphene (PLEG)-electrode, utilizing the laser-induced carbonization (LIC) technique on a thin (12.5 µm) polyimide (PI) surface at optimized laser parameters (laser power-22%, speed-5.2%, and gas flow-50%). The PI sheet was laminated on a polyethylene terephthalate (PET) sheet with silicone adhesive in the middle, helping to dissipate the heat generated during the carbonization process. Compared to conventional screen-printed platforms, the PLEG electrode provides higher surface area, receptor loading, electrical conductivity, ease of surface modification, and improved sensitivity with an average resistance of 40 ± 3 Ω/cm. Subsequently, the connection pad and reference electrodes (RE) were coated with silver/silver chloride (Ag/AgCl) conductive paste for improved connection. The RE was stabilized by coating it with polyvinyl butyrate (PVB) and sodium chloride polymeric cocktail. Three working electrodes (WE) were designated as WE-1 (for IL6), WE-2 (for lactate), and WE-3 (for pH). The sensor construction was initiated with surface activation WEs in 0.50 M H2SO4 containing 0.10 M KCl as a supporting electrolyte by sweeping potential between 1.0 and -1.2 V vs. Ag/AgCl reference electrode. For IL-6 sensing, the WEs were incubated with freshly prepared 1-pyrenebutyric acid N-hydroxysuccinimide (PBASE) as a non-covalent crosslinker (10.0 mM) in dimethylformamide (DMF) for 3 hrs., followed by buffer wash (3 times) to remove any unbound crosslinker. Later, a monoclonal antibody to IL6 was immobilized using peptide bond formation between PBASE and the recognition element, passivated by incubating in Bovine serum albumin (BSA) to block non-specific binding. Upon binding, the antigen-antibody complex's formation results in a decrease in voltammetric signal of the redox signal, generating an IL6-dependent change in current. For lactate detection, an amperometric method utilizes a two-electrode electrochemical setup. The WE comprise a composite Glutaraldehyde/BSA/Lactate-Oxidase/Prussian Blue/PLEG-electrode (GA/BSA/LOx/PB/ PLEG). An Ag/AgCl-coated electrode serves as the RE, and counter electrodes (CE). For the pH sensor (PANI/PLEG), polyaniline (PANI) was electrodeposited at 0.80 V for 600 sec on an activated PLEG electrode washed with distilled water and coated with Nafion (0.25% v/v). For pH measurements, the open-circuit potential (OCP) was measured between the PANI/PLEG electrode and the RE.Post characterization, the sensor’s electrochemical measurements to detect IL6, lactate, and pH were performed in buffer, artificial interstitial fluid, porcine blood, and serum samples with portable potentiostat. Under optimal experimental conditions, the devised platform showed a sensitivity of 2.59 µA/(log10IL6), 0.021 µA/mM, and ~49.39 ± 2 mV in spiked serum for IL6, lactate, and pH, respectively. Subsequently, serum samples of porcine VCA recipients were collected on postoperative days (POD) 0, 2, and 6 and tested using the IL-6, lactate, and pH sensors, respectively. The sensors can successfully track the change in the levels of IL6 (increasing) and lactate (increasing) and the change in pH post-surgery and align with clinical observations of inflammation and ischemia post-allograft on POD6. The sensor results were also validated using commercial IL6 ELISA and lactate kits using the same samples and showed a correlation (r) of r = 0.9885 (n=3, for IL6) and r = 0.9896 (n=3, for lactate). Our results demonstrate that the developed miniaturized platform offers a portable, low-cost, robust, and multiplex sensing platform capable of quantifying predictive biomarkers post-VCA surgeries. This platform presents a promising, miniaturized, and cost-effective solution for the real-time monitoring of biomarkers in VCA models. KEYWORDS: Vascularized Composite Allotransplantation (VCA), Ischemia, Interleukin-6, Lactate, Electrochemical sensor, Porous laser engraved graphene, Multiplex sensing

Acute Rejection Episodes and Graft Survival Following Living Donor Liver Transplant

Acute Rejection Episodes and Graft Survival Following Living Donor Liver Transplant

Kidney transplantation in children and adolescents with C3 glomerulopathy or immune complex membranoproliferative glomerulonephritis: a real-world study within the CERTAIN research network

BackgroundComplement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40–50% of patients progressing to kidney failure within 10 years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation.MethodsIn this multicenter longitudinal cohort study of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, we compared the post-transplant outcomes of pediatric patients with C3G (n = 17) or IC-MPGN (n = 3) with a matched case–control group (n = 20).ResultsEleven of 20 children (55%) with C3G or IC-MPGN experienced a recurrence within 5 years post-transplant. Patients with C3G or IC-MPGN had a 5-year graft survival of 61.4%, which was significantly (P = 0.029) lower than the 5-year graft survival of 90% in controls; five patients with C3G or IC-MPGN lost their graft due to recurrence during this observation period. Both the 1-year (20%) and the 5-year (42%) rates of biopsy-proven acute rejection episodes were comparable between patients and controls. Complement-targeted therapy with eculizumab, either as prophylaxis or treatment, did not appear to be effective.ConclusionsThese data in pediatric patients with C3G or IC-MPGN show a high risk of post-transplant disease recurrence (55%) and a significantly lower 5-year graft survival compared to matched controls with other primary kidney diseases. These data underscore the need for post-transplant patients for effective and specific therapies that target the underlying disease mechanism.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Heart-liver transplantation using the en bloc technique: A single-center experience over two decades

BackgroundCombined heart-liver transplantation (CHLT) is a definitive therapy reserved for patients with concomitant heart failure and advanced liver disease. A limited number of centers perform CHLT, and even fewer use the en bloc implantation technique. Here we review clinical outcomes and immunoprotective effects following CHLT and describe our institution's more than two decades of experience in performing the en bloc technique. MethodsAll patients who underwent CHLT at our institution between January 2003 and July 2023 were identified. Recipient and donor characteristics, operative details, and clinical outcomes were assessed. Kaplan-Meier analysis was performed to evaluate survival following CHLT. ResultsA total of 20 patients underwent CHLT using the en bloc technique at our institution between January 2003 and July 2023. At a median follow-up of 3.8 years for patients who survived the perioperative period (n = 18), estimated survival was 94% at 1 year and 75% at 5 years. There was 100% freedom from acute moderate rejection, acute severe rejection, and chronic rejection in all patients. No patients required retransplantation due to rejection. ConclusionsCHLT is a definitive therapy reserved for patients with multiorgan dysfunction. At our institution, the en bloc technique is the preferred operative approach, as it minimizes cardiac insult, requires fewer anastomoses, minimizes cold ischemia time, and allows for rapid correction of coagulopathy. Overall survival for this cohort is excellent. Episodes of acute rejection were rare, providing further support for the idea that the liver may serve an immunoprotective role in multiorgan transplantation.

Cytomegalovirus Retinitis in the Modern Era of Solid Organ Transplantation

BackgroundCytomegalovirus retinitis (CMVR) is a well-described complication of CMV disease in immunocompromised hosts. While robust data exists for CMVR in patients with acquired immunodeficiency syndrome (AIDS), the incidence and risk factors for CMVR in solid organ transplant recipients (SOTR) with CMV viremia are less defined. MethodsWe performed a retrospective cohort study of SOTR who had CMV viremia and underwent routine ophthalmologic examination between 1/1/2018 and 3/16/2022. Univariate statistics were performed to evaluate risk factors for development of CMVR. ResultsOverall, 38 patients were included, primarily kidney (78.9%), heart (7.9%), and liver (7.9%) transplant recipients. Five patients (13.2%) developed CMVR during the study period. CMVR was diagnosed an average 281 days after index transplantation, 84 days from the most recent rejection episode, and 69 days from onset of viremia. Only 1 patient (20%) had symptoms at the time of CMVR diagnosis. CMVR was associated with preceding allograft rejection as well as transplanted organ type. ConclusionWhile CMV tissue disease more commonly manifests in other organs, CMVR occurred relatively frequently in this group of high-risk SOTR with CMV viremia. As most of the patients in our study did not have ocular symptoms at the time of diagnosis, routine ophthalmologic screening should be considered in SOTR with CMV viremia.

Managing Post-Transplant Diabetes Mellitus after Kidney Transplantation: Challenges and Advances in Treatment.

Kidney transplantation is the most effective treatment for end-stage renal failure but is associated with complications, including post-transplant diabetes mellitus (PTDM). It affects the quality of life and survival of patients and the transplanted organ. It can cause complications, including infections and episodes of acute rejection, further threatening graft survival. The prevalence of PTDM, depending on the source, can range from 4 to 30% in transplant patients. This article aims to discuss issues related to diabetes in kidney transplant patients and the latest treatments. Knowledge of the mechanisms of action of immunosuppressive drugs used after transplantation and their effect on carbohydrate metabolism is key to the rapid and effective detection of PTDM. Patient therapy should not only include standard management such as lifestyle modification, insulin therapy or pharmacotherapy based on well-known oral and injection drugs. New opportunities are offered by hypoglycemic drugs still in clinical trials, including glucokinase activators, such as dorzagliatin, ADV-1002401, LY2608204, TMG-123, imeglimine, amycretin and pramlintide. Although many therapeutic options are currently available, PTDM often creates uncertainty about the most appropriate treatment strategy. Therefore, more research is needed to individualize therapeutic plans and monitor these patients.

Frequency and Outcome of Emergency Penetrating Keratoplasty in Infectious Keratitis in Sweden During the 21st Century.

To study the frequency over time and outcome of penetrating keratoplasty (PK), "keratoplasty à chaud," in patients with infectious keratitis with 2-year follow-up data. This register-based study included keratitis cases that had undergone PK in Sweden between 2001 and 2020 and reported to the Swedish Corneal Transplant Register. During the study period, 69 eyes were subjected to acute PK due to progressive infectious keratitis. The number increased from 2 annual procedures in the first half of the study period to 5 in the second half (P = 0.01). Preoperative corneal perforation was present in 43.5% (n = 30) of the eyes. Two years after surgery, follow-up data were completed in the register for 53 eyes; of these, 62.3% (n = 33) were considered to have functioning grafts, and 20.8% (n = 11) had experienced a rejection episode. The visual acuity improved from hand motion to counting fingers (P = 0.002), and the proportion of eyes with a visual acuity of ≤1.0 logMAR increased from 5.7% (n = 3) before the surgery to 45.3% (n = 24) at the 2-year follow-up (P < 0.001). The number of active infectious keratitis cases undergoing keratoplasty à chaud increased in Sweden during the 21st century. Most of the cases were successful regarding the structural integrity of the bulb, that is, "had a saved eye" and even a functioning graft 2 years after corneal transplantation. The visual gain was distinct, albeit modest. In cases with severe infectious keratitis, and even a concomitant perforation in the cornea due to the infection, corneal transplantation should continue to be an option.

Interstitial Foci Expression of Indoleamine 2,3-Dioxygenase 1: A Potential Biomarker for Kidney Transplant Rejection.

(1) Background: Kidney transplantation is the best therapy for patients with end-stage renal disease, but the risk of rejection complicates it. Indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme involved in immune response modulation, has been suggested to play a role in transplant immunological injury. The aim of the study was to explore the expression of IDO1 in the interstitial foci of transplanted kidneys and its potential association with rejection episodes. (2) Methods: This retrospective study analysed kidney transplant biopsies from 121 patients, focusing on IDO1 expression in interstitial foci. Immunohistochemistry was used to detect IDO1, and patients were categorised based on IDO1 presence (IDO1-IF positive or negative). The incidence of rejection was compared between these groups. (3) Results: Patients with IDO1 expression in interstitial foci (IDO1-IF(+)) exhibited higher incidences of rejection 46/80 (57.5%) vs. 10/41 (24.34%) patients compared to IDO1-IF(-) patients, which was statistically significant with p = 0.0005. The analysis of antibody-mediated rejection showed that IDO1-IF(+) patients developed AMR at 12/80 (15%), while only 1 IDO1-IF(-) negative patient did (2,44%), with p = 0.035. T-cell-mediated rejection was also more common in IDO1-IF(+) patients 43/80 (53.75%) than in IDO1-IF(-) patients 7/41 (17.07%), with p = 0.0001. (4) Conclusions: IDO1 expression in interstitial foci of renal transplant biopsies is associated with a higher incidence of rejection, suggesting that IDO1 could serve as a potential biomarker for transplant rejection. These findings highlight the importance of IDO1 in immune regulation and its potential utility in improving the management of kidney transplant recipients.

Impact of COVID-19 on anti-HLA antibodies in kidney transplantation

The effects of COVID-19 on the immune profile of kidney transplant recipients are unknown. Immunosuppression adjustment during the illness can increase the risk for de novo donor-specific anti-HLA antibodies (DSA) and acute rejection episodes. This single-center retrospective study includes adult kidney transplant recipients diagnosed with COVID-19 between March 2020 and December 2022, screened for anti-HLA antibodies (AbHLA) pre-transplant and after COVID-19. Analyzed data comprised demographics, immunosuppressive therapy before and during the illness, hospitalization rate, and AbHLA specificity. Two hundred sixty-seven transplant recipients were included and divided according to the pre-transplant AbHLA profile: absent [PRA- (n = 206, 77%)], non-DSA (N = 46, 17%), and DSA+ (n = 15, 6%). The DSA+ group was younger (40.5 ± 16.5; PRA- 50.3 ± 13.4; non-DSA 49.3 ± 11.7 years; p = 0.02). The hospitalization rate was higher in groups with preformed AbHLA (DSA+ n = 8, 53%; non-DSA = 24, 52%; PRA- n = 54, 26%; p < 0.01). Immunosuppression was maintained in 222 (83%), withdrawn in 33 (12%), and reduced in 11 (4%) cases without difference among groups. Twenty-two (8%) cases of de novo DSA were observed after COVID-19 [PRA-, n = 16 (73%) and non-DSA, n = 6 (27%)]. In the DSA+ group, the AbHLA profile remained stable. There were 6 (2%) cases of post-COVID-19 antibody-mediated rejection (DSA+ n = 4, 66%; non-DSA n = 1, 17%, PRA- n = 1, 17%) without T cell-mediated rejection cases. Post-COVID-19 de novo DSA was more frequent in groups without pre-transplant AbHLA, not having association with changes in immunosuppressive therapy.

Analysis of Immunological Biomarkers Associated With Rejection After Uterus Transplantation in Human.

Uterus transplantation (UTx) is an emerging therapy for women with uterine infertility. However, critical questions remain with this procedure including the mechanisms involved in graft rejection. In this study, we analyzed the immune profile of ectocervical biopsies from 5 patients after UTx before and during their first episode of rejection using RNA sequencing, quantitative polymerase chain reaction, and imaging mass cytometry. We identified 530 upregulated and 207 downregulated genes associated with graft rejection. Enrichment databases revealed abnormalities of skin-associated genes and the immune system, in particular activation of T and B lymphocytes, and macrophages. Imaging mass cytometry confirmed these observations; in cervical biopsies of 3 women, rejection was associated with the presence of B-cell structures linked to tertiary lymphoid structures, and 2 biopsies from 1 woman with severe rejection episodes and poor prognosis of graft function (repeated miscarriage and implantation failures) were associated with an accumulation of HLA-DR- macrophages, producing granzyme B at the surface of the epithelium. We showed that rejection of a UTx graft was associated with major alterations of immune markers including the involvement of tertiary lymphoid structures, the most organized of which may be a sign of chronic rejection, and with an increase in HLA-DR- macrophages expressing granzyme B in the case of grade 3 rejection episodes according Mölne's classification. We identified potential emerging biomarkers to predict or diagnose graft rejection (Keratin 1 granzyme B, IL1β). These findings could lead to development of improved strategies for the identification, prevention, and/or treatment of uterus graft rejection.

Clinical profile and outcomes of rejection after deep anterior lamellar keratoplasty in keratoconus.

To report the clinical features and management outcomes of rejection after deep anterior lamellar keratoplasty (DALK). The clinical features, indications, predisposing risk factors, management, and outcome of six eyes of six patients with rejection after DALK were analyzed retrospectively. The median time of rejection from the day of surgery was 12 (range 3-36) months. Median duration of symptoms was 4 (range 2-28) days. The indication for DALK was keratoconus in all eyes. The clinical features at presentation included graft haze, vascularization, and melt at the graft-host junction. The risk factors noted were noncompliance to steroids in all eyes, vernal conjunctivitis (four eyes), and eccentric graft (one eye). The rejection episode reversed with topical steroids in all eyes and intravenous methylprednisolone in one eye. One eye developed secondary fungal keratitis after initial recovery and one eye had a second episode of rejection 3 months later, which resulted in progressive vessels and lipid keratopathy in the visual axis. The median best corrected visual acuity was 20/40 (range 20/30-20/200). Severe stromal rejection can present with graft melt. Repeat episodes of rejection can occur on sudden cessation of topical steroids. Prompt recognition of clinical signs and symptoms with timely management helps in quick reversal of the rejection episode. Reversal of graft rejection results in good visual outcomes.