Treatment Of Acute Cellular Rejection Research Articles

Usefulness of Diffusion-Weighted Imaging in Evaluating Acute Cellular Rejection and Monitoring Treatment Response in Liver Transplant Recipients.

Acute cellular rejection (ACR) is a significant immune issue among recipients following liver transplantation. Although diffusion-weighted magnetic resonance imaging (DWI) is widely used for diagnosing liver disease, it has not yet been utilized for monitoring ACR in patients after liver transplantation. Therefore, the aim of this study was to evaluate the efficacy of DWI in monitoring treatment response among recipients with ACR. This study enrolled 25 recipients with highly suspected ACR rejection, and all subjects underwent both biochemistry and DWI scans before and after treatment. A pathological biopsy was performed 4 to 24 h after the first MRI examination to confirm ACR and degree of rejection. All patients were followed up and underwent a repeated MRI scan when their liver function returned to the normal range. After data acquisition, the DWI data were post-processed to obtain the apparent diffusion coefficient (ADC) map on a voxel-by-voxel basis. Five regions of interest were identified on the liver parenchyma to measure the mean ADC values from each patient. Finally, the mean ADC values and biochemical markers were statistically compared between ACR and non-ACR groups. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the ADC and biochemical data in detecting ACR, and correlation analysis was used to understand the relationship between the ADC values, biochemical markers, and the degree of rejection. The histopathologic results revealed that 20 recipients had ACR, including 10 mild, 9 moderate, and 1 severe rejection. The results demonstrated that the ACR patients had significantly lower hepatic ADC values than those in patients without ACR. After treatment, the hepatic ADC values in ACR patients significantly increased to levels similar to those in non-ACR patients with treatment. The ROC analysis showed that the sensitivity and specificity for detecting ACR were 80% and 95%, respectively. Furthermore, the correlation analysis revealed that the mean ADC value and alanine aminotransferase level had strong and moderate negative correlation with the degree of rejection, respectively (r = -0.72 and -0.47). The ADC values were useful for detecting hepatic ACR and monitoring treatment response after immunosuppressive therapy.

Eosinophils restrain humoral alloimmunity after lung transplantation.

While the function of many leukocytes in transplant biology has been well defined, the role of eosinophils is controversial and remains poorly explored. Conflicting data exist regarding eosinophils' role in alloimmunity. Due to their prevalence in the lung, and their defined role in other pulmonary pathologies such as asthma, we set out to explore the role of eosinophils in the long-term maintenance of the lung allograft. We noted that depletion of eosinophils results in the generation of donor-specific antibodies. Eosinophil depletion increased memory B cell, plasma cell, and antibody-secreting cell differentiation and resulted in de novo generation of follicular germinal centers. Germinal center formation depended on the expansion of CD4+Foxp3-Bcl6+CXCR5+PD-1+ T follicular helper (Tfh) cells, which increase in number after eosinophil depletion. Mechanistically, we demonstrate that eosinophils prevent Tfh cell generation by acting as the dominant source of IFN-γ in an established lung allograft, thus facilitating Th1 rather than Tfh polarization of naive CD4+ T cells. Our data thus describe what we believe is a unique and previously unknown role for eosinophils in maintaining allograft tolerance and suggest that indiscriminate administration of eosinophil-lytic corticosteroids for treatment of acute cellular rejection may inadvertently promote humoral alloimmunity.

The First Collective Examination of Immunosuppressive Practices Among American Intestinal Transplant Centers.

Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices. All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed. Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21.1). Induction regimens varied widely. Thymoglobulin was the most common, used in the plurality of patients (85/211; 40.3%), but there was no consensus regimen. Similarly, regimens for the treatment of acute cellular rejection, antibody-mediated rejection, and graft-versus-host disease varied significantly between centers. We also evaluated differences in maintenance immunosuppression protocols, desensitization regimens, mammalian target of rapamycin use, antimetabolite use, and posttransplantation surveillance practices. Maintenance tacrolimus levels, stoma presence, and scoping frequency were not associated with differences in rejection events. Definitive association between treatments and outcomes, including graft and patient survival, was not the intention of this initial collaboration and is prevented by the lack of patient-level data and the presence of confounders. However, we identified trends regarding rejection episodes after various induction strategies that require further investigation in our subsequent collaborations. This initial collaboration reveals the extreme heterogeneity of practices among American ITx centers. Future collaboration will explore patient-level data, stratified by age and transplant type (isolated intestine versus multivisceral), to explore the association between treatment regimens and outcomes.

Cardiac Allograft Rejection: Strategies for Success in the Face of Immune Challenges.

Heart transplantation for patients with end-stage heart failure refractory to medical therapy has remained definitive treatment with significant advances in posttransplant care. Despite improvement in postoperative morbidity and mortality, acute cellular rejection (ACR) and antibody-mediated rejection (AMR) remain substantial challenges that can lead to allograft failure and patient mortality. Immunosuppressive agents have been the mainstay of both prevention and treatment for ACR and AMR; however, many challenges exist with traditional therapies. There are a multitude of molecular pathways involved in mediating the humoral and cellular response to rejection, offering various targets for treatment. This review summarizes therapies used in the management of ACR and AMR as extrapolated from use in induction therapy and treatment of other solid-organ transplant rejection. Future studies focused on cardiac transplant recipients are needed to expand therapeutic options.

Rabbit Antithymocyte Globulin for Treatment of Corticosteroid Refractory Acute Cellular Rejection After Lung Transplantation.

Chronic lung allograft dysfunction (CLAD) remains a major cause of death after the first year posttransplant, with acute cellular rejection (ACR) being a major risk factor for CLAD. We evaluated the use of rabbit antithymocyte globulin (rATG) for corticosteroid refractory ACR in lung transplant recipients. We retrospectively identified 112 adult lung transplant recipients who received rATG for refractory ACR after lung transplantation. The primary endpoint was the incidence of ACR on follow-up transbronchial biopsy. Secondary endpoints included freedom from ACR within 1 y post-rATG, CLAD progression at 1 y post-rATG, and all-cause mortality at 1 y post-rATG. A complete resolution of ACR was observed in 60.2% of patients, an improvement but not complete resolution in 22.1%, and no response on follow-up biopsy in 17.8%. Mean A grade 1 y post-rATG was 0.51 in complete responders, 1.01 in partial responders, and 2.19 in nonresponders ( P < 0.001). Complete responders had significantly less new or worsening CLAD at 1 y than partial responders (17% versus 40%; P = 0.02). All-cause mortality rate was 14.9% in complete responders, 40% in partial responders, and 30% in nonresponders ( P < 0.01). rATG appears to be an effective treatment of refractory ACR in lung transplant recipients. Failure to respond to rATG carries an increased risk of early CLAD and death.

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

Histologic features of allograft livers in patients treated for rejection before biopsy

Liver biopsy is essential for management in liver transplant patients with clinical features suspicious for acute cellular rejection (ACR). As more patients are transplanted for noninfectious indications, it has become increasingly common for them to receive treatment for presumed ACR before biopsy. The effect of pretreatment on the classic histologic triad of ACR's mixed portal inflammation, endothelialitis, and bile duct damage is not well described. Here we report a retrospective study of 70 liver transplant biopsies performed on 53 patients for suspected ACR between 2018 and 2021. Thirty-seven biopsies had a clinical diagnosis of ACR after biopsy. Pretreatment with steroids, antithymocyte globulin, or other increased immunosuppression was given before biopsy in 17 of 37 cases; 20 not-pretreated cases acted as controls. A representative hematoxylin and eosin-stained slide from each biopsy was reviewed independently in a blinded fashion by 3 hepatic pathologists, graded according to the Banff system, assigned a Rejection Activity Index (RAI), and assessed for other histologic features. We found that pretreated biopsies had significantly less portal inflammation (P<.001), less endothelialitis (P<.001), lower RAI (P<.001), and less prominent eosinophils (P=.048) compared to not-pretreated biopsies. There was no significant difference for the other examined variables, including bile duct inflammation/damage (P=.32). Our findings suggest that portal inflammation and endothelialitis become less prominent with pretreatment, whereas bile duct inflammation/damage may take longer to resolve. When evaluating biopsies for suspected ACR, the finding of bile duct inflammation/damage should raise the possibility of partially treated ACR, even in the absence of endothelialitis and portal inflammation.

T-cell infiltrate intensity is associated with delayed response to treatment in late acute cellular rejection in pediatric liver transplant recipients.

Late acute cellular rejection (ACR) is associated with donor-specific antibodies (DSA) development, chronic rejection, and allograft loss. However, accurate predictors of late ACR treatment response are lacking. ACR is primarily T-cell mediated, yet B cells and plasma cells (PC) also infiltrate the portal areas during late ACR. To test the hypothesis that the inflammatory milieu is associated with delayed response (DR) to rejection therapy, we performed a single-center retrospective case-control study of pediatric late liver ACR using multiparameter immunofluorescence for CD4, CD8, CD68, CD20, and CD138 to identify immune cell subpopulations. Pediatric liver transplant recipients transplanted at <17 years of age and treated for biopsy-proven late ACR between January 2014 and 2019 were stratified into rapid response (RR) and DR based on alanine aminotransferase (ALT) normalization within 30 days of diagnosis. All patients received IV methylprednisolone as an initial rejection treatment. Immunofluorescence was performed on archived formalin-fixed paraffin embedded (FFPE) liver biopsy tissue. Liver biopsies from 60 episodes of late ACR in 54 patients were included in the analysis, of which 33 were DR (55%). Anti-thymocyte globulin was only required in the DR group. The frequency of liver-infiltrating CD20+ and CD8+ lymphocytes and the prevalence of autoantibodies were higher in the DR group. In univariate logistic regression analysis, serum gamma-glutamyl transpeptidase (GGT) level at diagnosis, but not ALT, Banff score or presence of DSA, predicted DR. Higher serum GGT level, presence of autoantibodies, and increased CD8+ T-cell infiltration portends DR in late ACR treatment in children.

Real World Use of Extracorporeal Photopheresis After Heart Transplantation - Clinical Outcomes from a Seven Centre European Study

<h3>Purpose</h3> Extracorporeal photopheresis (ECP) is recommended by different apheresis and transplant societies based on study results from 1998 and 2006 as an adjunctive therapy in prevention and treatment of acute cellular rejection (ACR) after heart transplantation (HTx). At present, however, it is also used to treat antibody mediated rejection (AMR) with and without (+/-) donor specific antibodies (DSA). The aim of this study was to describe the real-world use of ECP across European heart transplant centres and assess its impact on clinical outcomes in the modern era of heart transplantation. <h3>Methods</h3> Seven transplant centres located in five European countries participated in this retrospective, explorative, single-arm chart review study of over 90 patients. All included patients received ECP after heart transplant in 2015 or later with a follow-up period of up to two years after the last ECP treatment. Data have been extracted from the medical charts covering patient characteristics, reasons for ECP treatment, ECP treatment schedule and duration, concomitant treatments, clinical outcomes (e.g. graft dysfunctions, rejections, survival, immune system, kidney function) as well as treatment related complications and safety. <h3>Endpoints</h3> The findings of the full study analysis from the largest known multi-centre study on ECP after HTx, will be presented for ECP treatment overall, and for the three sub-groups ACR, AMR (+/- DSA), and prevention of rejection. Endpoints that will be reported will include graft and overall survival, incidence of rejections, infections and complications, changes in rejection grading, improvements in graft function, and ECP related safety data.

Immunosuppression-Induced Pulmonary Alveolar Proteinosis Following Bilateral Lung Transplantation

<h3>Introduction</h3> Pulmonary alveolar proteinosis (PAP) has been described secondary to immunosuppression-induced macrophage dysfunction following lung transplantation. The incidence of infection is known to be increased in the setting of PAP. We present a case of immunosuppression-associated PAP in a lung transplant recipient with mycobacterium avium complex (MAC) infection, responsive to reduced immunosuppression, serial whole lung lavage, and MAC treatment. <h3>Case Report</h3> A 69-year-old male underwent bilateral lung transplantation for hypersensitivity pneumonitis (HP). He was never treated with mTOR inhibitor therapy. One year post-transplant, he developed intermittent cough and exertional dyspnea. CT scan showed new bilateral peribronchovascular groundglass opacities and interlobular septal thickening, initially concerning for recurrent HP. BAL fluid grew MAC on serial AFB cultures; infection cleared with treatment. Transbronchial biopsy showed A1B0 at the time of MAC infection, which cleared following treatment for acute cellular rejection. He developed increased groundglass opacities with superimposed thickened intra- and interlobular septae in polygonal shapes, "crazy paving" suggestive of pulmonary alveolar proteinosis. Exertional supplemental O2 requirement increased to 10 LPM. Milky-white opaque BAL fluid was noted on bronchoscopy. Transbronchial biopsies showed focal alveolar filling by granular eosinophilic material, consistent with PAP. GM-CSF Ab testing was negative. He had no history of hematologic malignancy, myelodysplastic syndrome, or hematopoietic cell transplantation. Exposure history was negative for dust. <h3>Summary</h3> Whole lung lavage showed cloudy BAL fluid that progressively cleared with continued lavage. Following ACR treatment, immunosuppression was weaned. Groundglass opacities resolved and allograft function improved. He weaned to 4 LPM O2 with exertion with reduction in respiratory symptoms.

PD-L1 (Programmed Death Ligand 1) as a Marker of Acute Cellular Rejection After Heart Transplantation.

PD-L1 (Programmed Death Ligand 1) as a Marker of Acute Cellular Rejection After Heart Transplantation.

Cell Free DNA Levels in Patients with Acute Rejection after Lung Transplantation

<h3>Purpose</h3> The incidence of acute cellular rejection (ACR) in lung transplant recipients (LTRs) remains about 33% in the first-year post-transplant, the highest for any organ transplant. Although acute rejection frequently responds to treatment, at the present time there is no reliable biomarker to non-invasively monitor response to therapy after ACR treatment . We hypothesized %ddcfDNA levels following acute rejection treatment can predict response to therapy. <h3>Methods</h3> We retrospectively collected clinical and histopathology data on lung transplant recipients treated for ACR who underwent %ddcfDNA testing as part of clinical care between March 2020 and August 2020. <h3>Results</h3> We identified a total of 14 LTRs that were treated for ACR and had a %ddcfDNA value available. One patient had only one %ddcfDNA and was excluded from the analysis. 11/13 patients also had available %ddcfDNA values after treatment. 10/11 of these patients demonstrated a decline in %ddcfDNA level following treatment of rejection(figure 1) The mean reduction in %ddcfDNA after treatment was 55% (Log₁₀ Ratio -0.35; 95% CI, 9% to 78%; p = 0.03). One patient had a significant increase in follow up %ddcfDNA level attributed to persistent ACR and antibody mediated rejection(AMR) requiring Anti-Thymocyte Globuline(ATG) treatment. Subsequent values for this patient also demonstrate that %ddcfDNA levels decrease following aggressive treatment of rejection. One patient(patient 6) had concurrent infection and rejection. <h3>Conclusion</h3> %ddcfDNA may to be a useful biomarker in evaluating allograft post rejection treatment. Persistent high levels are suggestive of ongoing ACR or AMR

Are Those with Primary Graft Dysfunction More Likely to Have Acute Cellular Rejection or Donor-Specific Antibodies after Heart Transplantation?

<h3>Purpose</h3> Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality following heart transplantation (HT). We sought to determine the association between PGD and incidence of acute cellular rejection (ACR) and development of <i>de novo</i> donor specific antibodies (DSA) within two years post-HTx. <h3>Methods</h3> Consecutive adult HT recipients (n=351) from 1/2010 to 7/2018 at a single center were included. Multi-organ and re-transplants were excluded. Definition of moderate and severe PGD was based on the 2014 ISHLT consensus, which includes dependence on extracorporeal membrane oxygenation or intra-aortic balloon pump. The primary outcome was the incidence of ACR (ISHLT grade 2R or 3R) and the development of <i>de novo</i> DSA (mean fluorescence intensity >500) within 2 years post-HTx. <h3>Results</h3> The cohort was predominantly male (70.6%), with a mean age of 54.1±12.5 years; 34.6% had a durable left ventricular assist device as a bridge to HTx. There were 33 (9.1%) cases of moderate or severe PGD. HLA was assessed in a mean of 15 and 24 samples per patient in those with and without PGD respectively. At two years, patients with PGD had lower incidence of development of <i>de novo</i> DSA against HLA-C (1.6 vs. 3.2%, p=0.047), DP (1.3 vs. 4.3%, p=0.002), DQ (3.3% vs. 11.8%, p<0.001), DR (4.9 vs. 12.4%, p<0.001) compared to patients without PGD (Table 1). In patients with and without PGD, there were 7 and 8 endomyocardial biopsies performed per patient, respectively within two years post-HTx. Patients with PGD had similar incidence of ISHLT 2R or 3R ACR compared to those without PGD (5.3% vs. 3.1%, p=0.07). Finally, there was no difference in PGD among patients who received empiric treatment for ACR without positive endomyocardial biopsy results (3.1% in PGD vs. 3.7% in no PGD, p=0.47). <h3>Conclusion</h3> Development of <i>de novo</i> DSA was lower in the PGD group and there was no difference in overall incidence of ACR in patients with and without PGD at 2 years post-HTx.

The real incidence of biliary tract complications after adult liver transplantation: the role of the prospective routine use of cholangiography during post-transplant follow-up.

Biliary tract complications (BTCs) still burden liver transplantation (LT). The wide reporting variability highlights the absence of systematic screening. From 2000 to 2009, simultaneous liver biopsy and direct biliary visualization were prospectively performed in 242 recipients at 3 and 6months (n=212, 87.6%) or earlier when indicated (n=30, 12.4%). Median follow-up was 148 (107-182) months. Seven patients (2.9%) experienced postprocedural morbidity. BTCs were initially diagnosed in 76 (31.4%) patients; 32 (42.1%) had neither clinical nor biological abnormalities. Acute cellular rejection (ACR) was present in 27 (11.2%) patients and in 6 (22.2%) BTC patients. Nine (3.7%) patients with normal initial cholangiography developed BTCs after 60 (30-135) months post-LT. BTCs directly lead to 7 (2.9%) re-transplantations and 14 (5.8%) deaths resulting in 18 (7.4%) allograft losses. Bile duct proliferation at 12-month biopsy proved an independent risk factor for graft loss (P=0.005). Systematic biliary tract and allograft evaluation allows the incidence and extent of biliary lesions to be documented more precisely and to avoid erroneous treatment of ACR. The combination 'abnormal biliary tract-canalicular proliferation' is an indicator of worse graft outcome. BTCs are responsible for important delayed allograft and patient losses. These results underline the importance of life-long follow-up and appropriate timing for re-transplantation.

Role of Budesonide for the Treatment of Rejection in Pediatric Liver Transplantation.

Corticosteroids are an integral part of liver transplant (LT) immunosuppression regimens but are often accompanied by many adverse effects. Budesonide is an oral corticosteroid with extensive (80%-90%) hepatic first-pass metabolism and minimal systemic absorption. The aim of this study was to examine the safety and efficacy of budesonide for management of acute cellular rejection (ACR) in pediatric LT recipients. A retrospective descriptive analysis was performed for all pediatric patients who underwent LT at our center and were prescribed oral budesonide for the treatment of ACR. Alanine aminotransferase (ALT) values and documented adverse effects were reviewed. Twenty-nine patients were prescribed budesonide for the treatment of ACR; 65.5% with biopsy-proven acute rejection and 34.5% with presumed ACR. There was a significant decrease in ALT noted from the time of rejection when compared to values 1 month (P = 0.0011), 3 months (P = 0.0003), and 6 months (P = 0.0001) after treatment with budesonide. There was no difference noted between patient baseline ALT levels before rejection when compared to 1, 3, and 6 months posttreatment values suggesting resolution of rejection. Three patients required conversion from budesonide to systemic steroids. There were no discontinuations of budesonide secondary to adverse effects. Oral budesonide may be a promising alternative to systemic corticosteroids for the management of mild/moderate ACR and for empiric treatment of ACR in select pediatric LT recipients. Data from this study may provide the foundation for larger, prospective, multicenter trials to assess the effectiveness of budesonide in the treatment of ACR.

Bronchoalveolar Lavage Markers of Inflammation Early Post Lung-Transplant are Associated with CLAD and Death

Surveillance bronchoscopies with bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) are used in the evaluation of patients after lung transplant to detect acute cellular rejection (ACR) or infection. We have previously shown that a focused BAL protein signature early post-transplant may predict CLAD or death in a subset of clinically-stable patients with A1 ACR. The aim of the current study was to determine whether similar BAL markers would have similar predictive characteristics irrespective of ACR grade. The cohort consisted of all adult, first, bilateral lung transplants performed 2010-2017. Clinical status was categorized as unstable or stable based on presence or absence of ≥10% concurrent drop in FEV1. Clinically-stable patients with grade AX TBB (which are not routinely treated at our center, thus avoiding the confounding effect of ACR treatment) during the first-year post-transplant, not preceded by ACR (grade A≥1 or grade B≥1) were included. IL6, S100A8, IL10, TNF-receptor1, IL-1α, pentraxin3 and CXCL10, previously shown to be associated with worse outcomes, were measured in the BAL using a multiplex bead assay. Association with subsequent CLAD or death was assessed using Cox proportional hazards models adjusted for age, sex, native lung disease, and CMV-mismatch. 107 patients matched the inclusion criteria with a stable AX occurring at a median time of 188 days (IQR 96-279) post-transplant. Median time from AX TBB to CLAD or death was 462 (IQR 330, 928) and 582 days (IQR 251-1410), respectively. In multivariable models, levels of CXCL10 and IL10 were associated with both CLAD development and death while IL6, S100A8 and pentraxin3 were only associated with death (P<0.05 for all). A focused BAL protein signature in clinically-stable patients with ungradable TBB, early post-transplant, may be informative in determining a subset of patients who are at increased risk for worse outcome and may benefit from a more aggressive management strategy.

Diagnosi e trattamento del rigetto acuto cellulo-mediato nel trapianto di rene

The incidence of acute rejection of the kidney allograft in the world has been around 15% during the period between 2001 and 2003. It is clinically defined as an elevation in the level of serum creatinine by more than 0.3 mg/dL and is diagnosed by kidney biopsy. On pathologic examination, the interstitium of the allograft is diffusely edematous and infiltrated by CD4 and CD8 lymphocytes. Tubulitis occurs when the lymphocytes and monocytes extend into the walls and lumina of the tubules. Presence of leukocytes determines infection or antibody-mediated rejection. Typically C4d staining is negative. Other causes of acute allograft dysfunction included prerenal factors, interstitial nephritis, infection, acute tubular necrosis, toxicity by drugs, and obstruction in the urinary tract. The primary diagnostic assessments include history, especially adherence to immunosuppressive therapy, physical examination, blood and urine laboratory tests, measurement of the serum levels of the drugs, and ultrasonography. Diagnosis of acute cellular rejection depends on biopsy, CD20 staining for refractory cases, negative C4d staining, presence of markers of activating lymphocyte, and proteomic study. Treatment of acute cellular rejection in kidney transplant recipients include pulse steroid for the first rejection episode. It can be repeated for recurrent or resistant rejection. Thymoglobulin and OKT3 are used as the second line of treatment if graft function is deteriorating. Changing the protocol from cyclosporine to tacrolimus or adding mycophenolate mofetil or sirolimus might be effective. Prognosis depends on number of rejection episodes, the use of potent drugs, time of rejection from transplantation, and response to treatment.

Safe and Successful Treatment of Acute Cellular Rejection of an Intestine and Abdominal Wall Transplant With Vedolizumab.

Background.Graft survival rates after intestinal transplantation (ITx) are still the lowest in comparison to other solid organ transplants. One of the main reasons is the frequent occurrence of acute cellular rejection (ACR). Vedolizumab is an antibody against α4β7+ integrin involved in gut-homing of T cells which has been approved for inflammatory bowel diseases (IBD). We report its off-label use to treat ACR after ITx.Methods.Following abdominal wall transplantation (AWTx) and ITx, clinical course was followed biochemically. Sequential small intestinal biopsies were taken preceding, during, and after ACR treatment with vedolizumab, following the standard therapy regime for IBD. Rejection was diagnosed histologically, and proinflammatory (α4β7+, interleukin-17+) and regulatory (FoxP3+) T cells were analyzed by immunohistochemistry.Results.ACR in both the ITx and AWTx resolved upon vedolizumab treatment, which was safe, evidenced by clearing an astrovirus and primary cytomegalovirus infection. Only a slight reduction of α4β7+ cells in the mucosa was observed, and α4β7+ and regulatory T cells could still move into the lamina propria upon infection.Conclusions.Vedolizumab is a safe treatment option for ACR after ITx but its mechanism is probably not only based on inhibition of gut-selective T-cell homing.

Safety and Efficacy of Steroid Pulse Therapy for Acute Loss of FEV1 in Lung Transplant Recipients After Exclusion of Acute Cellular Rejection

BackgroundThe standard treatment of acute cellular rejection after lung transplantation (LTx) is a high-dose steroid pulse therapy. In our center, this therapy is also the standard of care for LTx recipients with acute loss of forced expiratory volume in 1 second (FEV1), after excluding specific causes such as acute rejection on biopsy. The aim of this retrospective study was to evaluate the safety and efficacy of steroid pulse therapy. MethodsFrom 2015 to 2018, 33 consecutive patients (17 male patients, mean age ± SD, 50.5 ± 12.5 years) were included. All patients underwent routine examinations to exclude acute cellular rejection and other specific causes. FEV1 was routinely measured after 5 days, and 1, 3, and 6 months. Positive response to steroid pulse therapy was defined by increase of FEV1 > 10%. ResultsThe mean decrease ± SD from baseline in FEV1 at the start of steroid pulse therapy was 380 ± 630 mL (P = .02). FEV1 changed after 5 days by 170 ± 180 mL (P = .0007), and after 1 month by 140 ± 230 mL (P = .70), 3 months by −60 ± 240 mL (P = .15), and 6 months by −80 ± 290 mL (P = .73). A positive response was observed in 21% of patients after 3 months and 12% after 6 months. High bronchoalveolar lavage (BAL) eosinophil count correlated with a higher FEV1 after steroid pulse therapy. Serious complications were observed in 4 out of 33 patients (12%) with 1 fatal event (pneumonia). ConclusionsOnly a minority of patients after LTx with loss of FEV1 after exclusion of acute cellular rejection benefit from steroid pulse therapy. Patients with BAL eosinophilia are more likely to respond. However, severe complications were observed.

2399 West Nile Encephalitis in a Post-Liver Transplant Patient

INTRODUCTION: West Nile Virus (WNV) is a neurotropic flavivirus that is transmitted from animals to humans by the bite of the Aedes, Anaphales, or Culex mosquito, with disease incidence peaking in the late summer and early fall. It is the leading cause of arboviral illness in the U.S. While many infected with WNV are asymptomatic, 25% of patients develop fever, and less than 1% of patients will develop neurologic symptoms. Age over 75-years old and immunosuppressed state are risk factors for developing neuroinvasive disease. CASE DESCRIPTION/METHODS: A 65-year old woman with a history of HCV cirrhosis complicated by HCC status post successful orthotopic liver transplantation (OLT) in 2016 compliant with tacrolimus and everolimus immunosuppression (ISP) presented with painless jaundice and acute transaminemia. Liver biopsy revealed severe acute cellular rejection (ACR), so steroids and thymoglobulin were started. Tacrolimus was increased and everolimus was changed to mycophenolate mofetil. Clinically, she appeared well and her LFTs responded to treatment. Suddenly, she developed fever to 103º associated with bilateral hand tremors. Infectious workup was obtained, and she was started on broad-spectrum antibiotics. Initially, symptoms were attributed to changes in ISP and treatment of ACR. However, she developed progressively worsening dyskinesia and encephalopathy eventually requiring intubation. Given initial negative infectious workup, lumbar puncture was obtained; see Table 1. HSV, VZV, and Lyme PCR as well as VDRL in the CSF were negative. Given clinical symptoms, positive WNV IgM in the CSF, and MRI Brain concerning for WNV neuroinvasive disease, patient was treated with IVIG for 5 days. WNV IgG became positive as well on repeat lumbar puncture 2 weeks later. Patient’s encephalopathy improved, and she was able to be extubated. DISCUSSION: There may be a delay in diagnosis and treatment of WNV encephalitis in post-liver transplant patients as neurologic symptoms may be attributed to ISP or as in this patient, to the treatment of acute cellular rejection. West Nile encephalitis must remain on the differential diagnosis when neurologic symptoms are present in a post-liver transplant patient, especially in endemic areas during the summer and fall months. A change in this patient’s ISP for the treatment of ACR may have caused the development of a more severe, neuroinvasive response to WNV infection and ISP management in such patients should be studied further.