Office or home versus 24-hour blood pressure measurement in stable kidney transplant recipients.

BACKGROUND AND HYPOTHESIS: The aim of this study was to quantify hypertension control and evaluate concordance between all commonly available blood pressure modalities in kidney transplant recipients (KTR). METHODS: For this prospective cross-sectional study 89 stable KTR were recruited at the Charité Transplant Outpatient Clinic. For each study participant office (manual office blood pressure 'MOBP' and automated office blood pressure 'AOBP'), 7-day home (HBPM) and 24-hour ambulatory blood pressure measurement (24h-ABPM) were performed. RESULTS: 80 of the 89 patients recruited had sufficient blood pressure recordings. Mean blood pressure for MOBP, AOBP, HBPM and 24h-ABPM was 129/73, 126/71, 131/85 and 130/81 mmHg, respectively. Uncontrolled hypertension, as defined by 24h-ABPM (mean ≥ 130/80 mmHg), was present in 53 (66%) patients. MOBP, AOBP and HBPM classified 19 (24%), 22 (28%) and 41 (51%) patients respectively as 'uncontrolled hypertensive'. The Bland-Altman plot showed good agreement between systolic MOBP, AOBP, HBPM and Daytime-ABPM (mean bias ± SD: -1 ± 13 mmHg, -4 ± 13 mmHg, 1 ± 10 mmHg, respectively). Uncontrolled nighttime hypertension was present in 74 (93%) KTR, with 71 (89%) patients showing a non-physiological dipping pattern. Moderate positive correlation between Daytime-ABPM/HBPM and Nighttime-ABPM (Pearson Correlation Coefficients: 0.62-0.73), followed by MOBP/AOBP (Pearson Correlation Coefficients: 0.49-0.59) was noted. eGFR and proteinuria displayed weak correlation with 24h-, Daytime- and Nighttime-ABPM (absolute values of Pearson Correlation Coefficients: 0.04-0.41). No robust association with either 24h-, Daytime- or Nighttime-ABPM was observed for volume status exams. CONCLUSIONS: Masked hypertension is highly prevalent in KTR, especially due to high rates of uncontrolled nighttime hypertension. HBPM shows the narrowest limits of agreement with Daytime-ABPM. Daytime-ABPM and HBPM show the highest, albeit clinically insufficient, correlation with Nighttime-ABPM. Systematic integration of 24h-ABPM into clinical practice, as proposed by the '2023 ESH Guidelines for the Management of arterial hypertension', should not be withheld for the KTR population. Clinical trials evaluating treatment of hypertension in KTR are urgently needed.

Comprehensive phytochemical profiles and antioxidant activity of Korean local cultivars of red chili pepper (Capsicum annuum L.).

Red chili pepper (Capsicum annuum L.), which belongs to the Solanaceae family, contains a variety of phytochemicals with health-promoting properties including capsaicinoids, phenolics and fatty acids. Red chili pepper is one of the most consumed vegetables in Korea and occupies the largest cultivated area among spices. In this study, the ethanolic extracts from two Korean local cultivars, namely Subicho and Eumseong, were analyzed using a hybrid trapped ion mobility Q-TOF mass spectrometer equipped with a UPLC system, and their phytochemical profiles were then compared with those of a common phytophthora disease-resistant cultivar called Dokbulwang, which is extensively used for red chili pepper powder in public spaces across Korea. Utilizing high-resolution ion-mobility Q-TOF MS analysis, 458 and 192 compounds were identified from the three different red chili peppers in positive and negative ion modes, respectively, by matching with a reference spectral library. Principal component analysis revealed clear distinctions among the three cultivars, allowing us to identify key phytochemical components responsible for discriminating the local cultivars from the public cultivar. Furthermore, the assessment of total flavonoid, phenolic, and antioxidant activity in the red pepper extracts, highlighted their diverse molecular and chemical profiles. Despite the higher total flavonoid and phenolic content values observed in the public cultivar, the radical scavenging rate was higher in the local cultivars, particularly in Subicho. This suggest the presence of stronger antioxidant compounds in the local cultivar, indicating their potential health benefits due to their rich content of bioactive compounds. Notably, the local cultivars exhibited significantly higher proportions of organic compounds (more than four times) and terpenoids (more than two times) compared to the public cultivar. Specifically, higher levels of five major capsaicinoid compounds were found in the local cultivars when compared to the public cultivar. The observed disparities in phytochemical composition and antioxidant activities indicate the molecular diversity present among these cultivars. Further exploration of the bioactive compounds in these local cultivars could prove invaluable for the development of native crops, potentially leading to the discovery of novel sources of bioactive molecules for various applications in health and agriculture.

Thermal responses of dissolved organic matter under global change.

The diversity of intrinsic traits of different organic matter molecules makes it challenging to predict how they, and therefore the global carbon cycle, will respond to climate change. Here we develop an indicator of compositional-level environmental response for dissolved organic matter to quantify the aggregated response of individual molecules that positively and negatively associate with warming. We apply the indicator to assess the thermal response of sediment dissolved organic matter in 480 aquatic microcosms along nutrient gradients on three Eurasian mountainsides. Organic molecules consistently respond to temperature change within and across contrasting climate zones. At a compositional level, dissolved organic matter in warmer sites has a stronger thermal response and shows functional reorganization towards molecules with lower thermodynamic favorability for microbial decomposition. The thermal response is more sensitive to warming at higher nutrients, with increased sensitivity of up to 22% for each additional 1 mg L-1 of nitrogen loading. The utility of the thermal response indicator is further confirmed by laboratory experiments and reveals its positive links to greenhouse gas emissions.

Successful topical minoxidil treatment for hair density and length in trichorhinophalangeal syndrome type 1.

A 9-year-old girl presented with slow hair growth and hair thinning since birth. Additionally, she had short stature and abnormally short fingers; genetic testing confirmed the diagnosis of trichorhinophalangeal syndrome (TRPS) type 1. After 4 months of topical minoxidil treatment, hair density and length significantly improved diffusely throughout the scalp without evidence of hypertrichosis. This case underscores the therapeutic potential of topical minoxidil for TRPS, paving the way for improved patient quality of life.

Topical Management of Pediatric Psoriasis: A Review of New Developments and Existing Therapies.

Psoriasis is a chronic immune-mediated disorder that commonly affects adults and children. In recent years, pediatric psoriasis has increased in prevalence and the disease is often associated with various comorbidities and psychological distress. The conventional topical treatments for psoriasis, such as corticosteroids, calcineurin inhibitors, vitamin D analogs, anthralin, and coal tar, are often limited by their side effects, tolerability, and/or efficacy, particularly for use in children and on sensitive and intertriginous areas. Recently, the US Food and Drug Administration approved two new topical non-steroidal agents for treating psoriasis that target different pathogenic pathways than the conventional treatments. Roflumilast is a phosphodiesterase type 4 inhibitor approved for the treatment of plaque psoriasis in patients aged 12 years and older. Tapinarof is a novel aryl hydrocarbon receptor modulator approved for adult psoriasis and currently undergoing studies for pediatric psoriasis. Ongoing efforts are also being made to optimize conventional treatments, for instance, a new foam formulation of halobetasol propionate was recently approved for pediatric psoriasis. Clinical trials of various new drugs targeting one or multiple pathogenic pathways of psoriasis, such as Janus kinase inhibitors, different formulations of phosphodiesterase type 4 inhibitors, and aryl hydrocarbon receptor modulators have also been explored. The recent emergence of novel topical agents provides promising new options for managing pediatric psoriasis with the potential to improve clinical outcomes and quality of life. In this article, we review the mechanism of action, efficacy, and safety profile of novel topical agents and discuss their potential roles in the management of pediatric psoriasis.

Nasal instillation of povidone-iodine ameliorates ongoing mucosal inflammation in a pre-sensitized murine model of Der p1-induced allergic rhinitis.

BACKGROUND: Interleukin (IL)-33, when cleaved into smaller fragments by proteases, becomes hyperactive, contributing to allergic inflammation. Povidone-iodine (PVP-I) is an iodine-based compound that exhibits antimicrobial properties and inhibits proteases. This study aimed to investigate whether PVP-I treatment inhibits IL-33 cleavage, improves allergic rhinitis (AR) symptoms, and suppresses allergic inflammation in a mouse model. METHODS: In vitro experiments using full-length recombinant human IL-33 and allergens, including house dust mites or Dermatophagoides pteronyssinus 1, were conducted using western blotting. Fifty BALB/c mice were divided into five groups: control (CON), AR with phosphate-buffered saline treatment (AR), PVP-I treatment (AR + PVP), trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E64) treatment (AR + E64), and dexamethasone treatment (AR + Dexa). Nasal symptom scores, including rubbing and sneezing, were measured. The cytokine levels in the nasal lavage fluid (NLF) and the concentration of immunoglobulins in the blood serum were assessed. Nasal mucosa from each group was used for reverse transcriptase-polymerase chain reaction (RT-PCR) and histological analyses were conducted. RESULTS: PVP-I treatment reduced nasal symptoms, suppressed allergic inflammation, and decreased the levels of IL-33, IL-5, and IL-13 in the NLF and total immunoglobulin E (IgE) and specific IgE in the serum. Histopathological analysis revealed a reduction in the number of eosinophils and goblet cells in the nasal mucosa of the AR + PVP group when compared to the AR group. RT-PCR and immunofluorescence staining confirmed the downregulation of genes and proteins associated with allergic inflammation. CONCLUSIONS: These findings suggest that nasal irrigation with PVP-I may be a promising therapeutic option for managing AR by inhibiting IL-33 activation and suppressing allergic inflammation.

COVID-19 Outcomes in Kidney Transplant Recipients in a German Transplant Center.

Kidney transplant recipients (KTRs) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTRs. Between 1 February 2020 and 1 July 2022, 578 KTRs were infected with SARS-CoV-2, with 25 (4%) recurrent infections. In total, 208 KTRs (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed that being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas a steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both virological changes in the Omicron variant and vaccination reduce the risk for morbidity and mortality from COVID-19 in KTRs. Our data extend the knowledge from the general population to KTRs and provide important insights into outcomes during the Omicron era.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Predictors of graft failure after first detection of de novo donor-specific HLA antibodies in kidney transplant recipients.

BACKGROUND: De novo donor-specific antibodies (dnDSAs) may cause antibody-mediated rejection and graft dysfunction. Little is known about the clinical course after first detection of dnDSAs during screening in asymptomatic patients. We aimed to assess the value of estimated glomerular filtration rate (eGFR) and proteinuria to predict graft failure in patients with dnDSAs and their potential utility as surrogate endpoints. METHODS: All 400 kidney transplant recipients with dnDSAs at our centre (1 March 2000-31 May 2021) were included in this retrospective study. The dates of graft loss, rejection, doubling of creatinine, ≥30% eGFR decline, proteinuria ≥500 mg/g and ≥1000 mg/g were registered from the first dnDSA appearance. RESULTS: During 8.3 years of follow-up, graft failure occurred in 33.3% of patients. Baseline eGFR and proteinuria correlated with 5-year graft loss (area under the receiver operating characteristics curve 0.75 and 0.80, P < .001). Creatinine doubled after a median of 2.8 years [interquartile range (IQR) 1.5-5.0] from dnDSA and the time from doubling creatinine to graft failure was 1.0 year (IQR 0.4-2.9). Analysing eGFR reduction ≥30% as a surrogate endpoint (148/400), the time from dnDSA to this event was 2.0 years (IQR 0.6-4.2), with a positive predictive value (PPV) of 45.9% to predict graft loss, which occurred after 2.0 years (IQR 0.8-3.2). The median time from proteinuria ≥500 mg/g and ≥1000 mg/g to graft failure was identical, 1.8 years, with a PPV of 43.8% and 49.0%, respectively. Composite endpoints did not improve PPV. Multivariable analysis showed that rejection was the most important independent risk factor for all renal endpoints and graft loss. CONCLUSIONS: Renal function, proteinuria and rejection are strongly associated with graft failure in patients with dnDSA and may serve as surrogate endpoints.

Risk Factors for Hepatitis E Virus Infection and Eating Habits in Kidney Transplant Recipients.

There is a significant risk for ongoing and treatment-resistant courses of hepatitis E virus (HEV) infection in patients after solid organ transplantation. The aim of this study was to identify risk factors for the development of hepatitis E, including the dietary habits of patients. We conducted a retrospective single-center study with 59 adult kidney and combined kidney transplant recipients who were diagnosed with HEV infection between 2013 and 2020. The outcomes of HEV infections were analyzed during a median follow-up of 4.3 years. Patients were compared with a control cohort of 251 transplant patients with elevated liver enzymes but without evidence of an HEV infection. Patients' alimentary exposures during the time before disease onset or diagnosis were assessed. Previous intense immunosuppression, especially treatment with high-dose steroids and rituximab, was a significant risk factor to acquire hepatitis E after solid organ transplantation. Only 11 out of 59 (18.6%) patients reached remission without further ribavirin (RBV) treatment. A total of 48 patients were treated with RBV, of which 19 patients (39.6%) had either viral rebounds after the end of treatment or did not reach viral clearance at all. Higher age (>60 years) and a BMI ≤ 20 kg/m2 were risk factors for RBV treatment failure. Deterioration in kidney function with a drop in eGFR (p = 0.046) and a rise in proteinuria was more common in patients with persistent hepatitis E viremia. HEV infection was associated with the consumption of undercooked pork or pork products prior to infection. Patients also reported processing raw meat with bare hands at home more frequently than the controls. Overall, we showed that the intensity of immunosuppression, higher age, a low BMI and the consumption of undercooked pork meat correlated with the development of hepatitis E.

Can we predict postinflammatory hyperpigmentation after laser treatment based on dermoscopic findings of solar lentigo?

Solar lentigo (SL) commonly occurs as hyperpigmented macules in areas exposed to ultraviolet radiation. It typically shows an increased number of melanocytes in the basal cell layer of the skin, with or without elongated rete ridges. This retrospective study aimed to evaluate the characteristic dermoscopic patterns, reflecting different histopathological features, which might be valuable in predicting the possibility of postinflammatory hyperpigmentation (PIH) occurring after laser treatment. In total, 88 Korean patients diagnosed with biopsy-proven SL (a total of 90 lesions were diagnosed) between January, 2016 and December, 2021 were included. Histopathological patterns were classified into six categories. Dermoscopic features were classified into six categories. Pseudonetwork pattern and rete ridge elongation showed a statistically significant negative correlation. This means that a flatter epidermis is likely to manifest as a pseudonetwork pattern. The erythema pattern showed a significant positive correlation with interface changes and inflammatory infiltration. Bluish-gray granules (peppering), a characteristic dermoscopic finding, showed significant positive correlations with interface changes, inflammatory infiltration, and dermal melanophages. Clinicians considering laser treatment for patients with SL should perform dermoscopic tests before treatment. The pseudonetwork relates to flattened epidermis and fewer Langerhans cells; thus, a lower remission of PIH after laser treatment might be expected. If bluish-gray granules or erythema are observed, inflammatory conditions are likely to be involved. In such cases, regression of the inflammatory response through drug therapy, such as topical corticosteroids, should be a priority option before laser treatment.

Pregnancy after Kidney Transplantation-Impact of Functional Renal Reserve, Slope of eGFR before Pregnancy, and Intensity of Immunosuppression on Kidney Function and Maternal Health.

Women of childbearing age show increased fertility after kidney transplantation. Of concern, preeclampsia, preterm delivery, and allograft dysfunction contribute to maternal and perinatal morbidity and mortality. We performed a retrospective single-center study, including 40 women with post-transplant pregnancies after single or combined pancreas-kidney transplantation between 2003 and 2019. Outcomes of kidney function up to 24 months after the end of pregnancy were compared with a matched-pair cohort of 40 transplanted patients without pregnancies. With a maternal survival rate of 100%, 39 out of 46 pregnancies ended up with a live-born baby. The eGFR slopes to the end of 24 months follow-up showed mean eGFR declines in both groups (-5.4 ± 14.3 mL/min in pregnant versus -7.6 ± 14.1 mL/min in controls). We identified 18 women with adverse pregnancy events, defined as preeclampsia with severe end-organ dysfunction. An impaired hyperfiltration during pregnancy was a significant risk contributor for both adverse pregnancy events (p < 0.05) and deterioration of kidney function (p < 0.01). In addition, a declining renal allograft function in the year before pregnancy was a negative predictor of worsening allograft function after 24 months of follow-up. No increased frequency of de novo donor-specific antibodies after delivery could be detected. Overall, pregnancies in women after kidney transplantation showed good allograft and maternal outcomes.

Insertions and deletions in the hypervariable region of the hepatitis E virus genome in individuals with acute and chronic infection.

BACKGROUND AND AIMS: Hepatitis E virus is a major cause of acute hepatitis worldwide and can progress to chronicity in immunocompromised individuals. Various virus-host recombination events have been reported in the hypervariable region of the hepatitis E virus genome, but the patterns of assembly and selection remain unclear. METHODS: To gain further insight into viral evolution, we assessed the presence of low abundance variants in 16 samples from individuals with acute or chronic infection using a targeted next-generation sequencing approach. RESULTS: In seven samples, different variants with insertions and/or deletions were identified. Among them, eight insertions originating either from human genes or from the hepatitis E virus genome. Five different deletions could be identified. The amino acid composition of sequences with insertions showed a higher frequency of lysine and a lower abundance of proline, and additionally acetylation and ubiquitination sites were more frequent than in hepatitis E virus wild-type sequences. CONCLUSIONS: These findings suggest that the nucleotide composition of insertions and sites for post-translational modification may contribute to recombination events. Although the impact of low-level hepatitis E virus variants is uncertain, our results highlight the importance of a highly sensitive next-generation sequencing approach to capture the full diversity of hypervariable region.

Inotodiol suppresses allergic inflammation in allergic rhinitis mice.

BACKGROUND: Inotodiol has been proven to have antitumor, antiviral, anti-inflammatory, and antiallergic properties. This study investigated the immunomodulatory capability of inotodiol in allergic rhinitis (AR) mice. METHODS: Forty BALB/c mice were divided into four groups, 10 mice each: control (CON), AR with phosphate-buffered saline (PBS) treatment (AR), inotodiol treatment (AR+Ino), and dexamethasone treatment (AR+Dex). Episodes of sneezing and nose rubbing were counted. Cytokines in nasal lavage fluid (NLF) and immunoglobulin in blood serum were measured. Nasal mucosae from each group were used for protein, reverse transcriptase-polymerase chain reaction (RT-PCR), and histological analyses. Splenocytes were cultured for evaluation of cytokine production in each group. RESULTS: Symptoms of rubbing and sneezing improved in the group of AR+Ino and AR+Dex than in the AR. NLF in the AR+Ino and AR+Dex also showed a significant decrease in interleukin (IL)-5, IL-10, and IL-13 compared to the AR. In addition, the number of eosinophils, goblet cells, and mast cells were notably lower in the nasal mucosae of the AR+Ino and AR+Dex. IL-4 and IL-17A in the AR+Ino and AR+Dex groups were decreased compared to the AR. Chemokines related to mast cell degradation were also decreased in the AR+Ino and AR+Dex groups. Total immunoglobulin (Ig)E, specific IgE and ovalbumin (OVA)-specific IgG1, and histamine levels were also significantly lower in the AR+Ino and AR+Dex groups. IL-10 and IL-13 were notably increased in the splenocytes of the AR after OVA stimulation, whereas the other groups showed no change. CONCLUSION: These results indicate inotodiol can help suppress allergic responses by immunomodulation activities.

Letermovir Rescue Therapy in Kidney Transplant Recipients with Refractory/Resistant CMV Disease.

(1) Background: CMV infections remain a problem after kidney transplantation, particularly if patients are refractory or resistant (r/r) to treatment with valganciclovir (VGCV) or ganciclovir (GCV). (2) Methods: In a single-center retrospective study, kidney transplant recipients (KTR) receiving letermovir (LTV) as rescue therapy for VGCV-/GCV-r/r CMV disease were analyzed regarding CMV history, immunosuppression, and outcomes. (3) Results: Of 201 KTR treated for CMV between 2017 and 2022, 8 patients received LTV following treatment failure with VGCV/GCV. All patients received CMV prophylaxis with VGCV according to the center's protocol, and 7/8 patients had a high-risk (D+/R-) CMV constellation. In seven of eight cases, rising CMV levels occurred during prophylaxis. In seven of eight patients, a mutation in UL97 associated with a decreased response to VGCV/GCV was detected. In four of eight patients, LTV resulted in CMV clearance after 24 ± 10 weeks (16-39 weeks), two of eight patients stabilized at viral loads <2000 cop/mL (6-20 weeks), and two of eight patients developed LTV resistance (range 8-10 weeks). (4) Conclusion: LTV, which is currently evaluated for CMV prophylaxis in kidney transplantation, also shows promising results for the treatment of patients with VGCV/GCV resistance despite the risk of developing LTV resistance. Additional studies are needed to further define its role in the treatment of patients with CMV resistance.

The natural history of de novo donor-specific HLA antibodies after kidney transplantation.

Background: De novo donor-specific HLA antibodies (dnDSA) are key factors in the diagnosis of antibody-mediated rejection (ABMR) and related to graft loss. Methods: This retrospective study was designed to evaluate the natural course of dnDSA in graft function and kidney allograft survival and to assess the impact of mean fluorescence intensity (MFI) evolution as detected by annual Luminex® screening. All 400 kidney transplant recipients with 731 dnDSA against the last graft (01/03/2000-31/05/2021) were included. Results: During 8.3 years of follow-up, ABMR occurred in 24.8% and graft loss in 33.3% of the cases, especially in patients with class I and II dnDSA, and those with multiple dnDSA. We observed frequent changes in MFI with 5-year allograft survivals post-dnDSA of 74.0% in patients with MFI reduction ≥ 50%, 62.4% with fluctuating MFI (MFI reduction ≥ 50% and doubling), and 52.7% with doubling MFI (log-rank p < 0.001). Interestingly, dnDSA in 168 (24.3%) cases became negative at some point during follow-up, and 38/400 (9.5%) patients became stable negative, which was associated with better graft survival. Multivariable analysis revealed the importance of MFI evolution and rejection, while class and number of dnDSA were not contributors in this model. Conclusion: In summary, we provide an in-depth analysis of the natural course of dnDSA after kidney transplantation, first evidence for the impact of MFI evolution on graft outcomes, and describe a relevant number of patients with a stable disappearance of dnDSA, related to better allograft survival.

In vitro and in vivo evidence that the switch from calcineurin to mTOR inhibitors may be a strategy for immunosuppression in Epstein-Barr virus-associated post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder is a life-threatening complication of immunosuppression following transplantation mediated by failure of T cells to control Epstein-Barr virus (EBV)-infected and transformed B cells. Typically, a modification or reduction of immunosuppression is recommended, but insufficiently defined thus far. In order to help delineate this, we characterized EBV-antigen-specific T cells and lymphoblastoid cell lines from healthy donors and in patients with a kidney transplant in the absence or presence of the standard immunosuppressants tacrolimus, cyclosporin A, prednisolone, rapamycin, and mycophenolic acid. Phenotypes of lymphoblastoid cell-lines and T cells, T cell-receptor-repertoire diversity, and T-cell reactivity upon co-culture with autologous lymphoblastoid cell lines were analyzed. Rapamycin and mycophenolic acid inhibited lymphoblastoid cell-line proliferation. T cells treated with prednisolone and rapamycin showed nearly normal cytokine production. Proliferation and the viability of T cells were decreased by mycophenolic acid, while tacrolimus and cyclosporin A were strong suppressors of T-cell function including their killing activity. Overall, our study provides a basis for the clinical decision for the modification and reduction of immunosuppression and adds information to the complex balance of maintaining anti-viral immunity while preventing acute rejection. Thus, an immunosuppressive regime based on mTOR inhibition and reduced or withdrawn calcineurin inhibitors could be a promising strategy for patients with increased risk of or manifested EBV-associated post-transplant lymphoproliferative disorder.