Interleukin-2 Receptor Antibody Research Articles

316.5: Long Term Outcomes of Low Dose Anti-thymocyte Globulin And Anti-interleukin-2 Receptor Antibody Induction in Kidney Transplantation From Expanded Criteria Donors

Background: Using kidneys from expanded criteria donors (ECD) has been increased due to the shortage of donor organs but seemed to have poorer prognosis. The aim of this study was to evaluate the safety and efficacy of rabbit anti-thymocyte globulin (rATG) induction in kidney transplantation (KT) from ECD compared to anti IL-2 receptor antibody (basiliximab). Methods: We retrospectively analyzed 182 patients who underwent KT from ECDs between April 2004 and December 2020. The patients were categorized into two groups according to induction therapy modality. The basiliximab group (n=43) received basiliximab 20mg/kg on day 0 and 4, while low dose rATG group (n=139) received rATG 1.5mg/kg on day 0, 1, and 2. Both groups received tacrolimus, mycopheonolate, and steroids as maintenance immunosuppressive agents. Results: The mean donor age (60.6 vs 64.3, p = 0.007) and KDPI score (84.4 vs 90.0, p = 0.005) were higher in rATG group. Patients in rATG group showed more delayed graft function (11.6% vs 30.9%, p = 0.021) but no significant difference in biopsy proven acute rejection (41.9% vs 35.3%, p =0.546). However, graft survival rates (p = 0.88) and overall survival rates (p = 0.846) were not significantly different between the two groups. CMV infection rate seemed higher in rATG group, but graft survival rate was not influenced by CMV infection (p =0.677). Conclusion: Low dose rATG induction in KT from ECD resulted in comparable patient and graft survival despite the worse donor and recipient profile comparing to basiliximab induction. Therefore, low dose rATG can be considered as an effective and safe induction therapy in KT from ECD.

Abstract 3513: INBRX-121, a safe and efficacious molecular targeted cytokine that enhances NK cell-mediated tumor killing

Abstract IL-2 is a powerful cytokine that enhances the activity of and induces the expansion of tumoricidal effector cells including T and NK cells. Despite promising signs of activity, the clinical utility of IL-2 is limited due to severe treatment-associated toxicities including vascular leak syndrome and the concurrent expansion of immunosuppressive regulatory T cells, which blunts efficacy. We developed a molecular targeted cytokine (MTC) platform that combines an engineered IL-2 variant with reduced affinity for the IL-2 receptor and high affinity single-domain antibodies (sdAb) to restrict IL-2 receptor signaling to cells expressing the target antigen (termed cis-signaling). INBRX-121 is an MTC designed to deliver IL-2 to NK cells using an NKp46-specific sdAb as the targeting moiety. In vitro, INBRX-121 induces dose-dependent STAT5 phosphorylation and proliferation in NK cells with comparable potency to wild-type IL-2, while showing no NKp46-independent activity at concentrations of more than three magnitudes higher than that required for NK cell activity. INBRX-121 enhances NK cell activation and cytotoxic capacity, thereby reducing the NK-to-target cell ratio as well as the target receptor density needed for optimal tumor cell killing. Furthermore, INBRX-121 lowers the threshold for antibody-dependent cellular cytotoxicity (ADCC) and increases maximal target cell killing in combination with ADCC-competent antibodies to an extent that may lessen the need for Fc engineering to enhance binding to the low affinity CD16A variant. In vivo, INBRX-121 demonstrates potent anti-tumor activity with increased intra-tumoral NK cell accumulation and upregulation of NK cell activation markers. INBRX-121 monotherapy reduces primary tumor growth and the formation of metastasis, while combination with ADCC-competent antibodies further increases NK cell activity to convert tumor growth suppression into complete tumor elimination. INBRX-121 is well tolerated in rodents and non-human primates and no overt signs of toxicity have been observed in cynomolgus monkeys up to the highest administered dose of 30 mg/kg. Our MTC platform provides a novel path to overcoming the limitations of IL-2 therapy through the pinpointed delivery of IL-2 activity to target cells of interest. In the case of INBRX-121 this ensures potent enhancement of the naturally broad anti-tumor activity of NK cells, which have distinct advantages over T cell therapeutics. Unlike T cells, tumor recognition by NK cells is independent of MHC-presented antigens and can elicit immediate cytotoxic activity. Further, many of the toxicities associated with T cell therapeutics have not been observed with NK-centric treatments. INBRX-121 therefore provides a promising safe and efficacious treatment option for a broad array of cancer indications both as a monotherapy and in combination with ADCC-enabled antibodies. Citation Format: Heather Kinkead, Florian J. Sulzmaier, Anya Polovina, Nadja Kern, Angelica Sanabria, Jason Ho, Chelsie Macedo, Ryan Henderson, Abrahim Hussain, Rajay Pandit, William Crago, Emily Rowell, Brendan P. Eckelman. INBRX-121, a safe and efficacious molecular targeted cytokine that enhances NK cell-mediated tumor killing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3513.

Induction Therapy and Outcomes following Kidney Transplantation in Recipients of Previous Heart or Liver Transplants.

Introduction:Optimal induction for kidney transplantation in patients with previous nonrenal organ transplantation is unclear. We aimed to evaluate the impact of induction therapy on the outcomes following kidney transplantation in patients who underwent prior heart or liver transplantation.Methods:Using the UNOS database, patients who underwent isolated heart or liver transplant from 2000 to 2016 followed by subsequent kidney transplant and maintained on calcineurin inhibitor (CNI)/mycophenolic acid (MPA) regimen were identified and stratified into three groups according to the induction used for kidney transplant: No induction, induction with interleukin-2 receptor antibody (IL-2RA), or T-cell depleting induction with Thymoglobulin. The outcomes were compared between no induction vs. IL-2RA and T-cell depleting induction, and IL-2RA vs. T-cell depleting induction.Results:Adjusted risk for delayed graft function was significantly higher for T-cell depleting vs. no induction (OR 4.56, 95% CI 1.14–18.3, P = 0.03) and trended higher for IL-2RA vs. no induction (OR 2.96, 95% CI 0.84–10.33, P = 0.08) among kidney after heart group and significantly higher for T-cell depleting vs. no induction (OR 2.88, 95% CI 1.40–5.95, P = 0.004) and IL-2RA induction (OR 1.88, 95% CI 1.12–3.17, P = 0.02) among kidney after liver patients. Adjusted graft failure and patient death risks were similar in patients who got IL-2RA or depleting inductions vs. no induction and IL-2RA vs. depleting induction groups in kidney after heart and kidney after liver groups.Conclusions:The use of induction was not associated with graft or patient survival benefits for kidney transplantation in patients who had prior heart or liver transplants and maintained on CNI and MPA regimen.

Reduced calcineurin inhibitor exposure with antibody induction and recurrent hepatocellular carcinoma after liver transplantation

Background Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT), but post-LT tumor recurrence remains a concern. Early post-LT immunosuppression is suggested to affect recurrence risk. We evaluated the impact on HCC recurrence of an immunosuppression protocol introduced in 2010 with interleukin-2 receptor antibody (IL-2RA) induction and delayed-introduction of reduced-dose tacrolimus with mycophenolate. Methods We included consecutive HCC patients transplanted 2000–2017 in Gothenburg. The impact on HCC recurrence of IL-2RA induction and mean tacrolimus trough concentration during the first 20 post-LT days was analyzed by multivariable Cox regression and propensity score-adjusted analyses. Results The study comprised 235 patients (mean age 57 yrs, men 80%, mean MELD 13, within Milan criteria 57%). The cumulative 5-yr HCC recurrence rate among patients transplanted before and after 2010 were 28.6% and 19.7%, respectively. IL-2RA induction had no independent effect on HCC recurrence. High tacrolimus exposure (mean 20-day tacrolimus concentration ≥8ng/mL) was associated with increased HCC recurrence risk on univariable analysis (HR 2.22, 95% CI 1.23–4.01, p = .008), but was non-significant on multivariable analysis (p = .17). Outside Milan criteria, high tacrolimus exposure was significant for HCC recurrence (HR 3.68, 95% CI 1.34–10.11, p = .012) independently of tumor characteristics and AFP level. This was confirmed on multivariable propensity score-adjusted analysis. Conclusions Reduced early tacrolimus exposure, facilitated by IL-2RA induction, was associated with reduced risk for HCC recurrence among patients outside Milan criteria. Prospective studies are needed to confirm if early tacrolimus-minimization strategies can help reduce HCC recurrence rates and help extend transplant criteria.

Immunosuppression Regimen Use and Outcomes in Older and Younger Adult Kidney Transplant Recipients: A National Registry Analysis.

Although the population of older transplant recipients has increased dramatically, there are limited data describing the impact of immunosuppression regimen choice on outcomes in this recipient group. National data for US Medicare-insured adult kidney recipients (N = 67 362; 2005-2016) were examined to determine early immunosuppression regimen and associations with acute rejection, death-censored graft failure, and mortality using multivariable regression analysis in younger (18-64 y) and older (>65 y) adults. The use of antithymocyte globulin (TMG) or alemtuzumab (ALEM) induction with triple maintenance immunosuppression (reference) was less common in older compared with younger (36.9% versus 47.0%) recipients, as was TMG/ALEM + steroid avoidance (19.2% versus 20.1%) and mammalian target of rapamycin inhibitor (mTORi)-based (6.7% versus 7.7%) treatments. Conversely, older patients were more likely to receive interleukin (IL)-2-receptor antibody (IL2rAb) + triple maintenance (21.1% versus 14.7%), IL2rAb + steroid avoidance (4.1% versus 1.8%), and cyclosporine-based (8.3% versus 6.6%) immunosuppression. Compared with older recipients treated with TMG/ALEM + triple maintenance (reference regimen), those managed with TMG/ALEM + steroid avoidance (adjusted odds ratio [aOR], 0.440.520.61) and IL2rAb + steroid avoidance (aOR, 0.390.550.79) had lower risk of acute rejection. Older patients experienced more death-censored graft failure when managed with Tac + antimetabolite avoidance (adjusted hazard [aHR], 1.411.782.25), mTORi-based (aHR, 1.702.142.71), and cyclosporine-based (aHR, 1.411.782.25) regimens, versus the reference regimen. mTORi-based and cyclosporine-based regimens were associated with increased mortality in both older and younger patients. Lower-intensity immunosuppression regimens (eg, steroid-sparing) appear beneficial for older kidney transplant recipients, while mTORi and cyclosporine-based maintenance immunosuppression are associated with higher risk of adverse outcomes.

Interleukin-2 receptor antibody induction with early low dose tacrolimus preserves post-liver transplant renal function in at risk individuals

BackgroundRenal dysfunction post liver transplantation (LT) is common. We report our real-world experience of IL2Ra induction with immediate exposure to reduced dose tacrolimus used for patients with chronic kidney disease (CKD) and evolving acute kidney injury (AKI). MethodA single-centre retrospective analysis of elective adult LT from 1/1/17 to 31/12/17. The primary outcome measure was increase in CKD stage at month 6 post-LT, and secondary outcome was early biopsy proven acute rejection (BPAR). Results161 patients were included: 17 planned-IL2Ra for CKD; 38 unplanned-IL2Ra for AKI; and 106 standard immunosuppression. IL2Ra group had lower trough tacrolimus levels till month 3 post-LT. Patients receiving IL2Ra did not have an increased risk of increase in CKD class at month 6 (aOR 0.95, 95% CI 0.34–2.75, P = 0.92), or of early BPAR (aOR 0.53, 95% CI 0.19–1.32, P = 0.19). ConclusionIL2Ra induction with immediate exposure to reduced dose tacrolimus can be given to patients with CKD or early evolving AKI post-LT, with no greater attrition of renal function at 6 months or an increased risk of early BPAR when compared to standard IS. Longer-term outcome data is required, however this regimen can be considered for high risk LT recipients with CKD and AKI.

COVID-19 in kidney transplant recipients.

There is minimal information on coronavirus disease 2019 (COVID‐19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47‐67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID‐19 testing was 2822 days (IQR 1272‐4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X‐ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID‐19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals.

Mucosa-associated lymphoid tissue (MALT) lymphoma developing in ectopic mediastinal thyroid tissue: a case report

BackgroundNormally located in the neck, ectopic mediastinal thyroid tissue consists of very rare ectopic thyroid tissue that does not connect to the thyroid gland. A patient with mucosa-associated lymphoid tissue (MALT) lymphoma that has developed in mediastinal thyroid tissue, to our best knowledge, has not been previously reported.Case presentationA 67-year-old woman presented with a superior mediastinal mass that was revealed by chest computed tomography (CT), an optional examination she hoped, during a medical checkup. Contrast-enhanced CT scan performed in our hospital for close examination confirmed the presence of a 2 × 1.3 cm poorly enhanced mass anterior to the trachea during the arterial phase. Magnetic resonance imaging depicted low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. I-131 meta-iodobenzylguanidine did not accumulate in the mass. Serum levels of interleukin-2 receptor, catecholamine, and anti-acetylcholine receptor antibody were within the normal range. The mass was resected through a transverse neck incision for the diagnosis and treatment. The histopathological diagnosis of the specimen was ectopic mediastinal thyroid tissue associated with MALT lymphoma and chronic thyroiditis. Immunoglobulin heavy chain class switch recombination was identified. Fine-needle aspiration biopsy of the cervical thyroid showed chronic thyroiditis but not lymphoma. The patient’s postoperative thyroid function was normal. To date, the patient’s recovery has been uneventful, and she is being monitored without further treatment.ConclusionWe treated the patient with MALT lymphoma that developed in ectopic mediastinal thyroid tissue. This novel case illustrates a new differential diagnosis associated with ectopic mediastinal thyroid tissue.

Effect of Interleukin-2 Receptor Antibody Induction Therapy on Survival in Renal Transplant Patients Receiving Tacrolimus

Background: This study aims to assess outcomes of interleukin-2 (IL-2) receptor blocker induction therapy on allograft and patients’ outcomes in standard risk recipients in the tacrolimus era, analysing data form the British Renal Transplant Registry. Methods: The study population involved all standard-risk renal transplant patients from 2000 till 2015 who were registered in the UK transplant registry and followed up till May 2018. Standard risk transplants were defined as patients with <2DR mismatch, calculated reaction frequency <20%, live donors or donors after brain death and patients with no previous renal transplantation transplant. We used inverse probability weights to adjust different covariates between the groups. Cox regression analysis for adjusted data and treatment effects model were used to assess outcomes. Results: In all, 3,597 renal transplant patients were included in the study. Two groups were identified; induction group (n = 2,858) which included patients who received IL-2 receptor blocker induction therapy and the no-induction group (n = 739). There was no significant difference between both groups in terms of estimated glomerular filtration rate (eGFR) rate at 1-year post-transplant (correlation co-efficient = 1.224, 95% CI ranges from –0.347 to 2.796). Average eGFR was 59.922 mL/min/1.73 m² in the induction group (SD 29.171) and 64.557 mL/min/1.73 m² in the no-induction groups (SD 46.763). There was no significant difference between both groups regarding graft survival at 5 years post-transplant (hazard ratio [HR] 0.944, 95% CI ranges from 0.599 to 1.485, p = 0.804), patient survival at 5 years post-transplant (HR 0.809, 95% CI ranges from 0.477 to1.372, p = 0.433). Conclusion: In the standard risk renal transplant population, the IL2 receptor blocker induction regimen does not affect eGFR at 1 year or renal and graft outcomes at 5 years.

Immunological risk stratification and tailored minimisation of immunosuppression in renal transplant recipients

BackgroundThe efficacy and safety of minimisation of immunosuppression including early steroid withdrawal in kidney transplant recipients treated with Basiliximab induction remains unclear.MethodsThis retrospective cohort study reports the outcomes from 298 consecutive renal transplants performed since 1st July 2010–June 2013 treated with Basiliximab induction and early steroid withdrawal in low immunological risk patients using a simple immunological risk stratification and 3-month protocol biopsy to optimise therapy. The cohort comprised 225 low-risk patients (first transplant or HLA antibody calculated reaction frequency (CRF ≤50% with no donor specific HLA antibodies) who underwent basiliximab induction, steroid withdrawal on day 7 and maintenance with tacrolimus and mycophenolate mofetil (MMF), and 73 high-risk patients who received tacrolimus, MMF and prednisolone for the first 3 months followed by long term maintenance immunosuppression with tacrolimus and prednisolone. High-risk patients not undergoing 3-month protocol biopsy were continued on triple immunosuppression.ResultsSteroid withdrawal could be safely achieved in low immunological risk recipients with IL2 receptor antibody induction. The incidence of biopsy-proven acute rejection was 15.1% in the low-risk and 13.9% in the high-risk group (including sub-clinical rejection detected at protocol biopsy). One- year graft survival was 93.3% and patient survival 98.5% in the low-risk group, and 97.3 and 100% respectively in the high-risk group. Graft function was similar in each group at 1 year (mean eGFR 61.2 ± 23.4 mL/min low-risk and 64.6 ± 19.2 mL/min high-risk).ConclusionsImmunosuppression regimen comprising basiliximab induction, tacrolimus, MMF and prednisolone with early steroid withdrawal in low risk patients and MMF withdrawal in high risk patients following a normal 3-month protocol biopsy is effective in limiting acute rejection episodes and produces excellent rates of patient survival, graft function and complications.

Evidence of Interleukin-2-Receptor-Antibody Induction in Low-Risk Living Donor Kidney Transplantation: A Single-Center Pilot Study

BackgroundThe recommended standard immunosuppressive therapy for renal transplant recipients comprises an initial induction therapy mainly with an interleukin-2-receptor antibody (IL2-RA) and a triple maintenance therapy. With tacrolimus and mycophenolate acid it is unknown whether IL2-RA application affects the short- and long-term results. This question is addressed in the present analysis. MethodsFrom July 2007 to June 2019 a total of 127 living donor kidney transplant recipients meeting the center-specific definition of immunologic low risk situation (first transplantation, HLA-mismatch ≤3, panel reactive antibody ≤10%) were identified. In 83 recipients with a first-degree relationship to the donor we omitted the IL2-RA induction (IL2-RA-). The remaining 44 recipients, mostly not first-degree relatives, served as controls (IL2-RA+). Biopsy-proven acute rejection and long-term patient and graft survival rates were compared. ResultsBiopsy-proven acute rejection rates after 3 months were similar in both groups with 4.8% (IL2-RA-) vs 13.7% (IL2-RA+; P = .0937), including borderline rejection rates of 18.0% (IL2-RA-) vs 18.3% (IL2-RA+; P = 1.000), respectively. Ten-year long-term survival rates were comparable between the IL2-RA- and the IL2-RA+ group with 95.6% vs 93.5% (patient survival; P = .5465) and 92.1% vs 90.6% (death-censored graft survival; P = .8893). ConclusionFor low-risk living donor kidney transplant recipients with first-degree relationship to the donor, it is safe to omit induction therapy with IL2-RA.

Sequential Cohort Analysis After Liver Transplantation Shows de Novo Extended Release Tacrolimus Is Safe, Efficacious, and Minimizes Renal Dysfunction

We conducted a single-center, prospective sequential cohort analysis of adult patients undergoing LT during a change in protocol from de novo BDT to ERT, with a 6-month post-LT follow-up. A total of 160 transplanted patients were evaluated; 82 were in the BDT group and 78 were in the ERT group. The cohorts were matched for standard variables and a similar proportion in each group received induction interleukin-2 receptor antibody (36% and 31%). There were no significant differences in the measured outcomes of patient and graft survival, biopsy-proven acute rejection episodes, post LT diabetes, and toxicity. A significantly lower number of patients developed chronic kidney disease Stage3-4 in the ERT cohort compared with BDT cohort. In patients with pre-LT renal dysfunction who received antibody induction, estimated glomerular filtration rate decreased significantly in the BDT but not the ERT group. We show that once-daily ERT is as safe and efficacious as BDT in de novo LT but optimally conserves renal function post-LT.

Incidence, Risk Factors, and Outcomes of Kidney Transplant Recipients Treated With Both Basiliximab and Antithymocyte Globulin.

Background:Kidney transplant recipients are given induction therapy to rapidly reduce the immune response and prevent rejection. Guidelines recommend that an interleukin-2 receptor antibody (basiliximab) be the first-line agent and that a lymphocyte-depleting agent (antithymocyte globulin [ATG]) be reserved for those at high immunologic risk.Objective:To determine the incidence, risk factors, and outcomes for patients who receive both basiliximab and ATG for induction compared to either agent alone.Design:Retrospective cohort study.Setting:We used the transplant electronic medical record at the University of Alberta Hospital in Edmonton, Canada.Patients/samples/participants:We included incident adult kidney transplant recipients from 2013 to 2018.Measurements:We measured baseline characteristics, type, and dose of induction therapy used, estimated glomerular filtration rate (eGFR) at 1-year posttransplant, and outcomes of all-cause graft failure, death-censored graft failure, all-cause mortality, and death with a functioning graft.Methods:Differences between induction groups were compared using chi-square test for categorical variables and Kruskal-Wallis tests for continuous variables. We performed multivariable logistic regression modeling with type of induction therapy as the dependent variable and the case-level factors as the predictors (adjusted odds ratio). We estimated the Kaplan-Meier failure functions and used log-rank tests to assess statistical significance of differences in unadjusted incidence across induction therapy types. We compared cumulative incidence functions using a Fine and Gray competing risk regression model.Results:In all, 430 kidney transplant recipients were followed for a mean of 3.9 years (standard deviation 1.5). Of these, 71% (n = 305) received basiliximab alone, 22% (n = 93) received ATG alone, and 7% (n = 32) received both basiliximab and ATG. After adjusting for age and sex, compared to the basiliximab alone group, patients were more likely to receive dual-induction therapy if they were sensitized (calculated panel reactive antibody ≥80%), had diabetes mellitus or peripheral vascular disease, or experienced delayed graft function. Compared to the ATG alone group, the dual-induction therapy group had worse graft function at 1 year (mean eGFR 42 vs. 59 mL/min/1.73 m2, P = .0008) and an increased risk of all-cause graft failure (31% vs. 13%, P = .02) and death-censored graft failure (16% vs. 4%, P = .03).Limitations:There is a risk of confounding by indication, as patients who received dual-induction therapy likely had worse outcomes due to the indication for dual-induction therapy (such as delayed graft function).Conclusions:In our study, 1 out of 10 recipients who were treated with basiliximab also received ATG for induction therapy. These patients experienced worse outcomes than those treated with ATG alone.Trial registration:Not applicable (cohort study).

Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study.

The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft. We enrolled in this prospective parallel-arm cohort study 28 subjects with type 1 diabetes who received islet transplantation either alone (ITA) or after a kidney graft (IAK). Islet transplantation consisted of two or three intraportal infusions of allogenic islets administered within (median [interquartile range]) 68 days (43-92). Immunosuppression was induced with interleukin-2 receptor antibodies and maintained with sirolimus and tacrolimus. The primary outcome was insulin independence with A1C ≤6.5% (48 mmol/mol). Secondary outcomes were patient and graft survival, severe hypoglycemic events (SHEs), metabolic control, and renal function. The primary outcome was met by (Kaplan-Meier estimates [95% CI]) 39% (22-57) and 28% (13-45) of patients 5 and 10 years after islet transplantation, respectively. Graft function persisted in 82% (62-92) and 78% (57-89) of case subjects after 5 and 10 years, respectively, and was associated with improved glucose control, reduced need for exogenous insulin, and a marked decrease of SHEs. ITA and IAK had similar outcomes. Primary graft function, evaluated 1 month after the last islet infusion, was significantly associated with the duration of graft function and insulin independence. Islet transplantation with the Edmonton protocol can provide 10-year markedly improved metabolic control without SHEs in three-quarters of patients with type 1 diabetes, kidney transplanted or not.

Serum neopterin as well as ferritin, soluble interleukin-2 receptor, KL-6 and anti-MDA5 antibody titer provide markers of the response to therapy in patients with interstitial lung disease complicating anti-MDA5 antibody-positive dermatomyositis

Objective: This study identified biomarkers that can be used to assess disease activity and response to therapy in patients with interstitial lung disease complicating anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive clinically amyopathic dermatomyositis (CADM).Methods: In 15 patients with interstitial lung disease complicating anti-MDA5 Ab-positive CADM, anti-MDA5 Ab, neopterin, interleukin (IL)-18, ferritin, and soluble interleukin 2 receptor (sIL-2R) levels were measured in cryopreserved serum specimens before and at multiple times after remission induction therapy, and their correlations were assessed.Results: Anti-MDA5 Ab, neopterin, IL-18, ferritin, and sIL-2R levels did not differ significantly between patients who survived and those who succumbed to the disease. In many cases, serum anti-MDA5 Ab titers were over the upper limit (over 150 index value) before treatment in the usual measuring method, and gradually decreased to the normal range at stable phase. Meanwhile, serum neopterin levels (21.6 [15.3–48.3] nmol/L) were significantly elevated in newly diagnosed patients and fell to 6.8 (5–11.4) nmol/L at 6 months after treatment introduction.Conclusions: Elevated serum neopterin as well as ferritin, sIL-2R, KL-6, and anti-MDA5 Ab titer might help identify patients with interstitial lung disease complicated with DM and might be useful in monitoring response to therapy.

Implication of interleukin-2 receptor antibody induction therapy in standard risk renal transplant in the tacrolimus era: a meta-analysis

BackgroundInterleukin-2 (IL-2) antagonist has been used as an induction therapy in many centres in calcineurin inhibitor-sparing regimens. Tacrolimus has overwhelmingly replaced cyclosporine in the maintenance immunosuppressive protocols in many transplant centres. The aim of our study and meta-analysis is to explore the effect of IL-2 induction therapy on the rate of rejection and patient and graft survival in standard-risk renal transplant patients with tacrolimus-based maintenance immunotherapy. Secondary aims included assessment of the effect of IL-2 induction therapy on creatinine change and the risk of cytomegalovirus (CMV) infection.MethodsWe conducted a systematic review in different databases to identify studies and research work that assessed the effect of IL-2 antibody induction therapy on renal transplant outcomes. Inclusion criteria for our meta-analysis were all studies that compared IL-2 induction therapy with placebo or no induction therapy in standard-risk renal transplant recipients on tacrolimus-based maintenance immunosuppressive therapy. Data collected were the name of the first author, journal title, year of publication, country where the study was conducted, number of patients in the IL-2 induction therapy arm and in the placebo arm, number of patients who had biopsy-proven rejection and graft survival in each arm. A random effects model was used for the meta-analysis.ResultsOf the 470 articles found in different databases, 7 were included in the meta-analysis. Forest plot analysis for rate of rejection during the follow-up period post-transplant showed no significant difference between the groups. There was no evidence of heterogenicity between included studies (I2 = 21.8%, P = 0.27). The overall risk difference was −0.02 [95% confidence interval (CI) −0.05–0.01]. A random effects meta-analysis for patient and graft survival was performed using forest plot analysis and showed no significant effect of IL-2 receptor (IL-2R) antibody induction on patient or graft survival compared with placebo. The overall risk difference was −0.01 (95% CI −0.04–0.01) and 0.00 (95% CI −0.00–0.01), respectively. Three of the included studies showed no effect of basiliximab on creatinine change, two showed no effect on risk of CMV infection and two showed less risk of post-transplant diabetes in the basiliximab group.ConclusionIL-2R antibody induction therapy has no significant effect on the rate of rejection or patient or graft survival in standard-risk renal transplant recipients on tacrolimus-based maintenance immunotherapy. More randomized controlled studies are needed.

P3.CR-31 A Case of Thymoma with Autoimmune Hepatitis Following Preoperative Chemotherapy

We encountered a case of thymoma with autoimmune hepatitis. A 63-year-old woman was found to have an abnormal finding on chest radiography during a medical checkup, but did not seek further care. She was referred to our hospital one year later when a bilateral hilar abnormality was again found during a checkup. Chest computed tomography (CT) showed a 4.6 × 3.0 × 5.6 cm mass with calcifications in the anterior mediastinum. The tumor invaded the right lung and middle lobe, in association with a 2.0-cm daughter nodule in the head of the main tumor, with multiple pleural seeding lesions in the right thoracic cavity. Although she was asymptomatic, the anti-acetylcholine receptor antibody level was elevated to 33 nmol/L and the soluble IL-2 receptor antibody was elevated to 1,700 U/mL. The mass was diagnosed with CT-guided biopsy as a type-B2 thymic tumor (cT3N0M1a, c-Stage IV). She underwent induction chemotherapy (ADOC, 2 courses). After chemotherapy, abnormal liver enzyme levels (aspartate aminotransferase: 451 U/L, alanine aminotransferase: 529 U/L) were noted on preoperative examination. She was diagnosed with autoimmune hepatitis based on liver biopsy findings and treated with oral prednisolone 30 mg. Surgery was performed after prednisolone dose was gradually decreased to 20 mg. Extended thymectomy and pulmonary wedge resection using median sternotomy were performed. Pleural dissemination was resected using video-assisted thoracoscopic surgery. The pathological findings showed type-B3 thymic carcinoma (pT3N0M1a, p-Stage IV, Masaoka classification IVa). She was placed under observation without any additional treatment. Prednisolone dose has been gradually decreased to 15 mg without exacerbation of liver function. The anti-acetylcholine receptor antibody level decreased after surgery. Autoimmune diseases in association with thymoma are well known, but reports of autoimmune hepatitis are very rare. Autoimmune hepatitis must be considered when acute liver damage is observed.

Role of induction therapy in low immunological risk-kidney transplant recipients: A mate-kidney analysis.

We aimed to evaluate the impact of induction on outcomes in low-immunological risk kidney transplant recipients (KTRs) using a mate-kidney model. Using OPTN/UNOS database, we identified three groups of low-immunological risk KTRs (first transplant, panel reactive antibody <20%, human leukocyte antigen mismatches ≤3) with each group containing recipients of mate-kidneys from same donor and differed by induction received: group 1: no induction vs interleukin-2 receptor antibody (IL2RA) induction; group 2: no induction vs depleting antibody induction; group 3: IL2RA vs depleting antibody induction. Outcomes were compared between mate-kidney recipients in each group in an adjusted model. Total of 1034 mate-kidney recipients were identified: group 1, n=192; group 2, n=362 and group 3, n=480. Adjusted risk for DGF was higher (OR 1.89, 95% CI 1.09-3.25,.P=0.02) and one-year acute rejection trended lower (OR 0.53, 95% CI 0.25-1.11, P=0.09) among depleting antibody induced patients in group 2. Adjusted five-year graft survivals were similar between mate-kidney recipients in all three groups. Adjusted patient death risk was significantly lower in depleting antibody induced patients in group 2 (HR 0.48, 95% CI 0.26-0.88, P=0.02) and trended lower in IL2RA induced patient in group 1 (HR 0.32, 95% CI 0.10-1.01, P=0.05). Perioperative antibody induction was associated with lower patient death risk in low-immunologic risk KTRs.

Safety and Efficacy of Induction Therapy With Thymoglobulin in AB0-Incompatible Kidney Transplantation

IntroductionData suggest an additional role of T cells in antibody-mediated rejections. In 2001 a protocol for AB0-incompatible kidney transplantation based on B-cell–depleting anti–CD20 antibody rituximab, antigen-specific blood group IgG immunoadsorption, intravenous immunoglobulins, and triple immunosuppression was introduced in Europe, which used induction therapy with the use of interleukin-2 receptor antibody (IL2-RA) basiliximab. We used thymoglobulin in AB0-incompatible patients as induction in the face of high immunologic risk. MethodsWe retrospectively evaluated a cohort of 9 AB0i living donation (LD) recipients from 2011 to 2014. Desensitization included blood group–specific immunoadsorption. Eighteen AB0-compatible LD recipients receiving induction therapy with thymoglobulin served as control subjects. Another control group consisted of 18 AB0-compatible LD recipients receiving basiliximab. Follow-up was 24 months. We captured graft function by estimating glomerular filtration rate (eGFR by Modification of Diet in Renal Disease formula), rejection episodes, and bacterial and viral infections. ResultsAll patients experienced immediate graft function. No significant or clinical differences were observed regarding graft function, rejection rates, or infections between the groups, although there seemed to be slightly higher cytomegalovirus infection rates due to preemptive therapy strategy. ConclusionsThymoglobulin appears to be similar in safety and efficacy to IL-2-antagonists in AB0i kidney transplantation.

Carcinoma of the Tongue in Renal Transplant Recipients: An Unusual Spectrum of De novo Malignancy at a Tertiary Care Center in India Over a Period of 26 Years.

Renal transplant recipients are at a higher risk of malignancy. We report our experience and the critical differences in the presentation of malignancy in kidney transplant patients performed at our tertiary care center and followed up over the period of 1990–2015. A total of 338 live donor transplants performed in 332 patients were analyzed. Induction immunosuppression was used in 22 cases with interleukin-2 (IL-2) receptor antibody. Overall 299 patients were continued on calcineurin inhibitor (CNI)-based triple drug immunosuppression, 33 were off CNI with 13 of them receiving sirolimus additionally. A total of 16 malignancies including post transplant lymphoproliferative disease (5), oral cancer (5), lung cancer (2), hepatobiliary cancer (2), colon cancer (1), and skin cancer (1) were diagnosed in 15 patients. Over the 26-year follow up, 138 patients died of whom 12 died due to cancer. Cancer occurred in 4.7% of patients but accounted for 9.4% of deaths. Oral cancer occurred after a significantly longer latency of over 10 years (212 vs. 94 months, P = 0.00652). Despite the longer latency, oral cancer patients were younger at diagnosis (44.0 vs. 52 years, P = 0.01016) and had better outcome (Fisher's exact test, P = 0.0275). This was despite a longer overall follow-up for the oral cancer patients, reflecting the better outcome for these patients (24 vs. 4 months, P = 0.0278). This might be the result of relatively early diagnosis of oral cancers.