Immunosuppressed Transplant Patients Research Articles

TTV and CMV viral load dynamics: Which emerges first during immunosuppression?

Novel biomarkers reflecting the degree of immunosuppression in transplant patients are required to ensure eventual personalized equilibrium between rejection and infection risks.With the above aim, Torque Teno Virus(TTV) viremia was precisely examined in a large cohort of transplanted immunocompromised patients (192 hematological and 60 solid organ transplant recipients) being monitored for Cytomegalovirus reactivation.TTV load was measured in 2612 plasma samples from 448 patients. The results revealed a significant increase in TTV viral load approximately 14 days following CMV reactivation/infection in solid organ transplant(SOT) patients. No recognizable difference in TTV load was noted among hematological patients during the entire timeframe analyzed. Furthermore, a temporal gap of approximately 30 days was noted between the viral load peaks reached by the two viruses, with Cytomegalovirus(CMV) preceding TTV.It was not possible to establish a correlation between CMV reactivation/infection and TTV viremia in hematological patients. On the other hand, the SOT patient cohort allowed us to analyze viral kinetics and draw intriguing conclusions. Taken together, the data suggest, to our knowledge for the first time, that CMV infection itself could potentially cause an increase in TTV load in the peripheral blood of patients undergoing immunosuppressive therapy.

Engineered HCMV-infected APCs enable the identification of new immunodominant HLA-restricted epitopes of anti-HCMV T-cell immunity.

Complications due to HCMV infection or reactivation remain a challenging clinical problem in immunocompromised patients, mainly due to insufficient or absent T-cell functionality. Knowledge of viral targets is crucial to improve monitoring of high-risk patients and optimise antiviral T-cell therapy. To expand the epitope spectrum, genetically-engineered dendritic cells (DCs) and fibroblasts were designed to secrete soluble (s)HLA-A*11:01 and infected with an HCMV mutant lacking immune evasion molecules (US2-6 + 11). More than 700 HLA-A*11:01-restricted epitopes, including more than 50 epitopes derived from a broad range of HCMV open-reading-frames (ORFs) were identified by mass spectrometry and screened for HLA-A*11:01-binding using established prediction tools. The immunogenicity of the 24 highest scoring new candidates was evaluated in vitro in healthy HLA-A*11:01+/HCMV+ donors. Thus, four subdominant epitopes and one immunodominant epitope, derived from the anti-apoptotic protein UL36 and ORFL101C (A11SAL), were identified. Their HLA-A*11:01 complex stability was verified in vitro. In depth analyses revealed highly proliferative and cytotoxic memory T-cell responses against A11SAL, with T-cell responses comparable to the immunodominant HLA-A*02:01-restricted HCMVpp65NLV epitope. A11SAL-specific T cells were also detectable in vivo in immunosuppressed transplant patients and shown to be effective in an in vitro HCMV-infection model, suggesting their crucial role in inhibiting viral replication and improvement of patient's outcome. The developed in vitro pipeline is the first to utilise genetically-engineered DCs to identify naturally presented immunodominant HCMV-derived epitopes. It therefore offers advantages over in silico predictions, is transferable to other HLA alleles, and will significantly expand the repertoire of viral targets to improve therapeutic options.

Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry.

Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients. Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-SNEG, IP-SPOSVLNEG and IP-SPOSVLPOS groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator®) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency. Polyfunctional CD8+ T cells indicated previous EBV contact (IP-SNEG 0.00% vs IP-SPOS 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-SNEG 0.01% vs IP-SPOS 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-SPOSVLPOS 0.43% vs IP-SPOSVLNEG 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-SNEG 0.00% vs IP-SPOS 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-SNEG patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-SPOSVLPOS patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81). Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults.

Intrauterine devices are a safe form of contraception in users with solid organ transplantation: A single-center experience.

Patients who undergo organ transplantation are advised to use contraception for health optimization, yet limited data exists on safe contraceptive options for this population. This study investigates the infection risk of intrauterine devices (IUDs) in patients who have received a solid organ transplant by evaluating the incidence of pelvic inflammatory disease (PID). We performed a retrospective chart review of subjects with a solid organ transplant who used an IUD between the years of January 2007 to February 2021. We included subjects ages 22-55 years at the time of IUD placement. We abstracted demographic information, transplant type, IUD type, immunosuppressive medications, screening for sexually transmitted infections, and diagnosis of PID. We identified 29 subjects that met the inclusion criteria. Six subjects had a copper IUD (21%) and 23 had a levonorgestrel IUD (79%). The most common organ transplanted was a kidney (n = 10) and liver (n = 10) while five subjects had multiple organs transplanted. Twenty-five (86.2%) subjects took immunosuppressive medications at the time of IUD insertion. Twenty-four (82.8%) patients had their IUD placed after transplantation. The average time of IUD use was 2.5 years. . In our study of IUD use in patients with solid organ transplantation, no patients developed PID. IUDs are a safe contraceptive option for immunosuppressed transplant patients.

Farnesyltransferase-inhibitors exert in vitro immunosuppressive capacity by inhibiting human B-cells.

Farnesyltransferase inhibitors (FTI), which inhibit the prenylation of Ras GTPases, were developed as anti-cancer drugs. As additional target proteins for prenylation were identified in the past, it is likely that FTI have potential value for therapeutic purposes beyond cancer. The effect of FTI on B-cells remains unclear. To address this issue, we investigated the effects of in vitro FTI treatment on effector and regulatory B-cells in healthy controls and renal transplant patients. For this purpose, B-cells were isolated from the peripheral blood of healthy controls and renal transplant patients. Purified B-cells were stimulated via Toll-like-receptor 9 (TLR-9) in the presence or absence of FTI. Regulatory functions, such as IL-10 and Granzyme B (GrB) secretion, were assessed by flow cytometry. In addition, effector B-cell functions, such as plasma cell formation and IgG secretion, were studied. The two FTI Lonafarnib and tipifarnib both suppressed TLR-9-induced B-cell proliferation. Maturation of IL-10 producing B-cells was suppressed by FTI at high concentrations as well as induction of GrB-secreting B-cells. Plasma blast formation and IgG secretion were potently suppressed by FTI. Moreover, purified B-cells from immunosuppressed renal transplant patients were also susceptible to FTI-induced suppression of effector functions, evidenced by diminished IgG secretion. FTI suppress in vitro B-cell proliferation and plasma cell formation while partially preserving IL-10 as well as GrB production of B-cells. Thus, FTI may have immunosuppressive capacity encouraging further studies to investigate the potential immunomodulatory value of this agent.

Outcomes of liver transplantation patients infected with COVID-19: pandemic hospital experience from Turkey

Aims: There are conflicting results for the course of the disease and mortality rates for liver transplantation patients infected with COVID-19. In this study, we aimed to present the outcomes of our liver transplant patients who were hospitalized and followed up in our tertiary hospital, which served as a pandemic hospital for COVID-19.
 Methods: Patients hospitalized with the diagnosis of COVID-19 between March 1, 2020 and March 1, 2022 in Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital and Prof. Dr. Feriha Öz Pandemic Hospital were included. In this retrospective observational study, the clinical data of the patients, the need for intensive care hospitalization, and mortality rates were recorded by hospital computer system. The relationships were analyzed with SPSS v20.0.
 Results: There were 25996 patients who were hospitalized with the diagnosis of COVID-19 and 28 of them were with the history of liver transplantation. Ages of the liver transplant patients ranged from 18 to 73, with a median age of 52. 82.1% of the patients were male and 17.9% were female. Intensive care unit hospitalization rate was 25% and mortality rate was 14.3%. The relationships according to the age groups revealed that all of the women were under the age of 50 (p=0.008) and the patients who deceased were male patients over the age of 50 (p=0.044).
 Conclusion: Mortality rates and intensive care unit requirements of chronically immunosuppressed liver transplant patients with COVID-19 infection were similar with general population. Complete immunosuppression withdrawal should not be urged in this population.

Transcatheter aortic valve replacement 23 years after heart transplant for aortic insufficiency

BackgroundClinicians continue to expand the availability of transcatheter aortic valve replacement (TAVR) for patients who historically would have been ineligible for surgical aortic valve replacement. Historically, reoperative aortic valve surgery after transplant was immensely complicated and high risk due to the repeat sternotomy approach, and the immunosuppression in transplant patients. As heart transplant patients continue to live longer, patients are beginning to develop novo aortic pathology of the transplanted organ. In these patients, TAVR may be a valuable rescue therapy for those with de-novo aortic valve disease.Case presentationHere, we present a single case of a 70-year-old man with a history of heart transplant 23 years prior complicated by severe sternal infection and subsequent removal of his sternum. Additionally, this patient had a recent history of kidney transplant due to renal cell carcinoma necessitating nephrectomy. He subsequently developed progressive symptomatic aortic insufficiency and underwent a successful TAVR to treat his new aortic disease.ConclusionsTo our knowledge, this represents only the second case report of TAVR for severe aortic insufficiency and one of the first reports of TAVR in a multiple organ recipient. TAVR may represent an important rescue therapy for post-transplant valve pathologies instead of high-risk reoperative surgical aortic valve replacement.

B-063 Towards Improving mRNA Vaccine Effectiveness in Immunosuppressed Adults: Elucidating the Mechanisms and Evaluating Potential Improvement Strategies

Abstract Background The success of COVID-19 mRNA vaccines (Co-mV) has provided a renewed impetus in developing “onetime universal flu, COVID”, and other mRNA-based vaccines to offer broader and long-lasting protection. However, to bring this endeavor to fruition, it is of prime importance to address the mechanism(s) underlying poor vaccine response in some patients and close this gap of inequitable effectiveness through improvement strategies, which is the focus of our current study. To date, there is no ‘empirical’ evidence to link the perturbation of translation, a rate-limiting step for mRNA vaccine efficiency, to its dampened response. Methods This IRB approved study involved 1) an assessment of a total of 1009 immunocompromised (IC) patients and immunocompetent subjects who had received 2 or more doses of Co-mV, 2) in vitro cell-culture experiments, and 3) in vivo animal studies. Impact of immunosuppressants (ISs), tacrolimus (T), mycophenolate (M), rapamycin/sirolimus (S), and their combinations on Pfizer Co-mV translation were determined by the Spike (Sp) protein expression following Co-mV transfection in HEK293 cells. In vivo impact of ISs on SARS-CoV-2 spike specific antigen (SpAg) and associated antibody levels (IgGSp) in serum were longitudinally assessed (26 days) in Balb/c mice after two doses (2D) of the Pfizer vaccine. Spike Ag and IgGSp levels were assessed in 259 IC patients and 50 healthy controls (HC) who received 2D of Pfizer or Moderna Co-mV. In addition, 67 immunosuppressed solid organ transplant (SOT) patients and 843 non-transplanted (NT) subjects following three doses (3D) of Co-mV were assessed. Expression of Sp and p70S6K phosphorylation (translation surrogate) were evaluated following higher vaccine doses and transient drug holidays. Statistical analysis was performed using GraphPad software 9.3.1. p < 0.05 was considered as statistically significant. Results The 2D and 3D Co-mV received IC patients showed a significantly lower IgGSP response (p < 0.0001) relative to their matched controls. M or S profoundly dampened (p < 0.001) the IgGSP response following Co-mV in the IC patients relative to those that were not on these drugs. M and S, when used individually or in combination in HEK293 cells, significantly (p < 0.05) attenuated the Co-mV-induced Sp expression concurrently with translation surrogates. In contrast, T did not change these indices. Notably, the cellular uptake of Co-Mv was not altered by these drugs. In vivo sirolimus combo pretreatment significantly (p < 0.05) attenuated the Co-mV induced IgMSp and IgGSp production. This correlated with a decreasing trend in the early levels (after day 1) of Co-mV-induced Sp immunogen levels. Neither higher Co-mV concentrations (6μg) nor a 1-day break of S could overcome the repressed Sp protein levels. Interestingly, 3-days of S holiday or using T alone rescued Sp levels in vitro. Conclusion This is the first study to reveal that ISs, sirolimus and mycophenolate restrain Co-mV-induced Sp protein synthesis via translation suppression. Transient holiday of sirolimus or selective use of tacrolimus at the time of vaccination can be a potential option to rescue translation-dependent Sp protein production. These compelling findings lay a solid foundation for guiding future studies aimed at improving mRNA-based vaccine effectiveness in high-risk IC patients.

Cell-free chromatin immunoprecipitation to detect molecular pathways in heart transplantation.

Existing monitoring approaches in heart transplantation lack the sensitivity to provide deep molecular assessments to guide management, or require endomyocardial biopsy, an invasive and blind procedure that lacks the precision to reliably obtain biopsy samples from diseased sites. This study examined plasma cell-free DNA chromatin immunoprecipitation sequencing (cfChIP-seq) as a noninvasive proxy to define molecular gene sets and sources of tissue injury in heart transplant patients. In healthy controls and in heart transplant patients, cfChIP-seq reliably detected housekeeping genes. cfChIP-seq identified differential gene signals of relevant immune and nonimmune molecular pathways that were predominantly down-regulated in immunosuppressed heart transplant patients compared with healthy controls. cfChIP-seq also identified cell-free DNA tissue sources. Compared with healthy controls, heart transplant patients demonstrated greater cell-free DNA from tissue types associated with heart transplant complications, including the heart, hematopoietic cells, lungs, liver, and vascular endothelium. cfChIP-seq may therefore be a reliable approach to profile dynamic assessments of molecular pathways and sources of tissue injury in heart transplant patients.

WTP2.1 Predictors Of Non -Adherence To Immunosuppression In Transplant Patients At A University Teaching Hospital

Abstract Introduction To assess the degree of immunosuppressive medication adherence in kidney transplant patients (KTPs) and to determine the predictors of non-adherence. Methods From a total of 106 KTPs treated at the RLBUHT (Jan 2020- June 2021), N= 20 (18%) patients were identified as being non-adherent on two or more hospital incident episodes identified by the continued care clinic, clinicians, and pharmacy. Statistical analysis was performed using the Student t-test. The predictors were data mined with Cox Regression, with the time-variable being time to graft dysfunction or Tacrolimus level abnormality > 50% variance of average trough level (6-8 ng/ml). Results Non-Adherence was observed in 20 (18.6%) patients; the estimated glomerular filtration rate was significantly lower in the no-adherence group (28.52 ± 17.62 ml/min) than in the adherence group (62.43 ± 11.72 ml/min, p < 0.05). About the Tacrolimus trough level, a significant difference was found between the adherers and the Nonadherers (5.10 ± 2.19 vs. 3.06 ± 1.04 ng/ml, p < 0.05). Non-adherers were interrogated during clinical encounters by clinicians and interpreter requirements. Polypharmacy (N=15), (Interpreter requirement) (N=11), young patients age 18-21 (N=05), and old age>70 (N=04) were the predictors of non-adherence. The patients were re-counseled and social services were involved to minimize recurrence. Conclusion The KTPs in this study demonstrated that non-adherence was associated with worse graft function and a lower Tacrolimus level. Knowledge about the degree of adherence could help identify non-adherent patients early and develop strategies to improve outcomes.

Kidney Transplant Practice in Pandemic Times: Lessons Learned for the Future.

Kidney Transplant Practice in Pandemic Times: Lessons Learned for the Future.

Natural history of intraductal papillary mucinous neoplasms following solid organ transplant

Background: Solid organ transplant (SOT) survival rates have improved with advances in immunosuppressive medications. Chronic immunosuppressive exposure, however, increases the risk of developing malignancies due to the loss of immune surveillance and/or the carcinogenic effects of these medications. Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic lesions that carry malignant potential. The long-term prospective for malignant transformation of IPMN in the setting of chronic immunosuppressive therapy is unclear. In this study, we aim to evaluate the natural history of IPMNs in immunosuppressed transplant patients.

Dental implant failure in immunosuppressed renal transplant patient: A case report

Background: In the literature, the dental implant survival rate has been reported one hundred percent in immunosuppressed patients after a solid organ transplant (SOT). There is no previously published dental implant failure that has been reported on immunosuppressed renal transplant, which is the most common SOT therapy. Case Report: The case presented is that of a 66-years old male edentulous patient suffering from lack of functional prosthesis and who received a renal transplant two years ago. No complications such as infection, radiolucency, or pus were detected after two dental implants were placed in the mandible and after three months recovery period. The right mandibular dental implant failure occurred due to compression of the dental implant and healing head during the delivery of the patient’s removable prosthesis. Following implant socket healing after two months, the 4.8 mm diameter implant was placed immediately after. Osseointegration was completed uneventfully, and the patient was successfully rehabilitated with a two implant-retained mandibular overdenture prosthesis. The implant restoration was performing well with stable Peri-implant bone levels have shown minimal marginal bone loss at a 2-year follow-up. Conclusion: Treatment of combined immunosuppressive medication used in renal transplant patients after dental implant rehabilitation, as well as accompanying chronic diseases, should be performed considering the possibility of failure in dental implant applications. In this case report, the causes of implant failure were reported patients who received dental implant treatment after renal transplantation from a cadaver. How to cite this article: Güler B, Özaltun B, Çukurluöz Bayındır B, Dal G. Dental implant failure in immunosuppressed renal transplant patient: A case report. Int Dent Res 2022;12(3):171-5. https://doi.org/10.5577/intdentres.2022.vol12.no3.10 Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.

Translation suppression underlies the restrained COVID-19 mRNA vaccine response in the high-risk immunocompromised group.

Immunocompromised (IC) patients show diminished immune response to COVID-19 mRNA vaccines (Co-mV). To date, there is no 'empirical' evidence to link the perturbation of translation, a rate-limiting step for mRNA vaccine efficiency (VE), to the dampened response of Co-mV. Impact of immunosuppressants (ISs), tacrolimus (T), mycophenolate (M), rapamycin/sirolimus (S), and their combinations on Pfizer Co-mV translation were determined by the Spike (Sp) protein expression following Co-mV transfection in HEK293 cells. In vivo impact of ISs on SARS-CoV-2 spike specific antigen (SpAg) and associated antibody levels (IgGSp) in serum were assessed in Balb/c mice after two doses (2D) of the Pfizer vaccine. Spike Ag and IgGSp levels were assessed in 259 IC patients and 50 healthy controls (HC) who received 2D of Pfizer or Moderna Co-mV as well as in 67 immunosuppressed solid organ transplant (SOT) patients and 843 non-transplanted (NT) subjects following three doses (3D) of Co-mV. Higher Co-mV concentrations and transient drug holidays were evaluated. We observed significantly lower IgGSP response in IC patients (p<0.0001) compared to their matched controls in 2D and 3D Co-mV groups. IC patients on M or S showed a profound dampening of IgGSP response relative to those that were not on these drugs. M and S, when used individually or in combination, significantly attenuated the Co-mV-induced Sp expression, whereas T did not exert significant influence. Sirolimus combo pretreatment in vivo significantly attenuated the Co-mV induced IgMSp and IgGSp production, which correlated with a decreasing trend in the early levels (after day 1) of Co-mV induced Sp immunogen levels. Neither higher Co-mV concentrations (6μg) nor withholding S for 1-day could overcome the inhibition of Sp protein levels. Interestingly, 3-days S holiday or using T alone rescued Sp levels in vitro. This is the first study to demonstrate that ISs, sirolimus and mycophenolate inhibited Co-mV-induced Sp protein synthesis via translation repression. Selective use of tacrolimus or drug holiday of sirolimus can be a potential means to rescue translation-dependent Sp protein production. These findings lay a strong foundation for guiding future studies aimed at improving Co-mV responses in high-risk IC patients.

Navigating Through the Complications of Chronic Immunosuppression in Transplant Patients

The advent of organ transplantation has given hope to patients with end-stage organ failure. Allograft rejection is a transplant complication and remains a significant cause of transplant-related morbidity and mortality. Successful transplantation is achieved with immunosuppression, and the discovery of newer immunosuppressive agents has provided transplant physicians with more effective medications in preventing allograft rejection. On the flip side, long-term immunosuppression is fraught with complications such as predisposition to infections, malignancies, and cardiovascular diseases. The patient presented in the case report developed a transplant-related lymphoma many years after his kidney and pancreatic transplant. Primary care providers should be aware of these complications and educate their patients on measures to prevent some of them.

Acyclovir induced thrombocytopenia and encephalopathy in a 76-year-old immunosuppressed renal transplant patient: A Case Report

Acyclovir induced thrombocytopenia and encephalopathy in a 76-year-old immunosuppressed renal transplant patient: A Case Report

BI01: Dupilumab in the management of atopic dermatitis in an immunosuppressed renal transplant patient

BI01: Dupilumab in the management of atopic dermatitis in an immunosuppressed renal transplant patient

Epstein-Barr Virus-Encoded BILF1 Orthologues From Porcine Lymphotropic Herpesviruses Display Common Molecular Functionality

Infection of immunosuppressed transplant patients with the human γ-herpesvirus Epstein-Barr virus (EBV) is associated with post-transplant lymphoproliferative disease (PTLD), an often fatal complication. Immunosuppressed miniature pigs infected with γ-herpesvirus porcine lymphotropic herpesvirus 1 (PLHV1) develop a similar disease, identifying pigs as a potential preclinical model for PTLD in humans. BILF1 is a G protein-coupled receptor (GPCR) encoded by EBV with constitutive activity linked to tumorigenesis and immunoevasive function downregulating MHC-I. In the present study, we compared BILF1-orthologues encoded by the three known PLHVs (PLHV1-3) with EBV-BILF1 to determine pharmacological suitability of BILF1 orthologues as model system to study EBV-BILF1 druggability. Cell surface localization, constitutive internalization, and MHC-I downregulation as well as membrane proximal constitutive Gαi signaling patterns were conserved across all BILFs. Only subtle differences between the individual BILFs were observed in downstream transcription factor activation. Using Illumina sequencing, PLHV1 was observed in lymphatic tissue from PTLD-diseased, but not non-diseased pigs. Importantly, these tissues showed enhanced expression of PLHV1-BILF1 supporting its involvement in PTLD infection.

Refractory bladder haemorrhage managed with cystoscopic diathermy in a patient with Ataxia-Telangiectasia and intercurrent BK polyomavirus infection

Ataxia telangiectasia (A-T) is a rare neurodegenerative immunodeficiency syndrome, characterised eponymously by progressive cerebellar ataxia and telangiectatic vessels, most often cutaneous. A-T displays autosomal recessive inheritance, is characterised by defective DNA repair due to mutations within the ATM gene on chromosome 11 [ 1 ]; and a lack of native ATM protein gives rise to the aforementioned hallmarks of the disease. With A-T comes a predisposition to haematological malignancy and humoral immunodeficiency, and as such these patients often suffer truncated lifespans [ 1 , 2 ]. Urological manifestations are rare, and intravesical involvement comprising bladder telangiectasia has only been described in a handful of cases, all of which have previously been treated with cyclophosphamide for malignancies, a known instigator of bladder haemorrhage [ [3] , [4] , [5] ]. Similarly, BK polyomavirus is a known precipitant of nephropathy and haemorrhagic cystitis in actively immunosuppressed renal transplant patients, though has not been established as such in genetically immunodeficient patients with native urological tissue [ 6 ]. Here we present, to our knowledge, the first case of refractory haemorrhagic cystitis in an A-T patient with intercurrent BK polyoma virus infection, who had previously been treated with cyclophosphamide for leukaemia, and propose that recurrent cystoscopic diathermy is a robust and relatively conservative surgical option to treat haemorrhagic cystitis secondary to bladder wall telangiectasia.

Post-transplant Lymphoproliferative Disorder Following Cardiac Transplantation.

Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of lymphoid conditions frequently associated with the Epstein Barr Virus (EBV) and the use of potent immunosuppressive drugs after solid organ transplantation. PTLD remains a major cause of long-term morbidity and mortality following heart transplantation (HT). Epstein-Barr virus (EBV) is a key pathogenic driver in many PTLD cases. In the majority of PTLD cases, the proliferating immune cell is the B-cell, and the impaired T-cell immune surveillance against infected B cells in immunosuppressed transplant patients plays a key role in the pathogenesis of EBV-positive PTLD. Preventive screening strategies have been attempted for PTLD including limiting patient exposure to aggressive immunosuppressive regimens by tailoring or minimizing immunosuppression while preserving graft function, anti-viral prophylaxis, routine EBV monitoring, and avoidance of EBV seromismatch. Our group has also demonstrated that conversion from calcineurin inhibitor to the mammalian target of rapamycin (mTOR) inhibitor, sirolimus, as a primary immunosuppression was associated with a decreased risk of PTLD following HT. The main therapeutic measures consist of immunosuppression reduction, treatment with rituximab and use of immunochemotherapy regimens. The purpose of this article is to review the potential mechanisms underlying PTLD pathogenesis, discuss recent advances, and review potential therapeutic targets to decrease the burden of PTLD after HT.