Pneumococcal vaccination is essential to prevent invasive Streptococcus pneumoniae infections in immunocompromised individuals, including kidney transplant recipients. Current recommendations favor single-dose immunization with higher-valent conjugate vaccines, including PCV20 or PCV21. Five years ago, sequential administration of the 13-valent conjugate vaccine (PCV13) followed by the 23-valent polysaccharide vaccine (PPSV23) represented standard of care. Long-term data on antibody persistence after this regimen remain limited. In this prospective 5-year follow-up study, 46 kidney transplant recipients previously vaccinated sequentially with PCV13 and PPSV23 were re-evaluated. Nine patients were lost to follow-up, and 11 had died during the observation period. The remaining 26 participants were re-enrolled and completed the 5-year assessment. Global and serotype-specific IgG anti-pneumococcal antibody concentrations were quantified and compared with baseline and 12-month post-vaccination levels. Clinical outcomes, including pneumococcal infections and allograft status, were recorded. Five years after vaccination, antibody concentrations remained above baseline levels in most participants. Mean IgG levels were still approximately threefold higher than pre-vaccination values. Even for serotype-specific responses, mean antibody levels showed minimal changes compared with those measured 12 months after the first vaccination, although absolute titers remained considerably lower than those observed in healthy individuals. No cases of pneumococcal pneumonia or vaccine-associated allograft rejection occurred during follow-up. Sequential vaccination elicits durable immune responses in kidney transplant recipients, persisting up to 5 years post-immunization. With the availability of new vaccines covering additional serotypes, and given the generally lower antibody responses in this high-risk population, a booster with PCV20 or PCV21 appears advisable to enhance and broaden protection.IMPORTANCEKidney transplant recipients are at high risk for invasive pneumococcal disease, yet long-term vaccine-induced immunity in this population remains poorly defined. This study provides one of the longest longitudinal assessments of humoral responses following sequential PCV13 and PPSV23 vaccination, extending to 5 years post-immunization. We demonstrate sustained but heterogeneous antibody persistence and serotype-dependent responses to PCV20 booster vaccination. These results are directly relevant to transplant clinicians, vaccinologists, and public health policy, offering critical insight into long-term pneumococcal immunity in immunocompromised hosts and guiding future vaccine scheduling in solid organ transplantation.

Increasing evidence suggests that reactivation of latent EBV in patients with COVID-19 may be linked to the development of post-acute sequelae of COVID-19, colloquially known as Long COVID. However, the reason for this co-occurrence of primary infection and reactivation of latent viruses remains elusive. During the first wave of COVID-19, we assessed all major immune cell populations by flow cytometry in a cohort of 61 patients with moderate to critical COVID-19 at the time of hospitalization. Additional blood samples from these patients were biobanked for later analysis. Using these biobanked samples, we evaluated the co-occurrence of CMV, EBV, as well as HHV-6A and -6B by qPCR. EBV was found to be reactivated not only in patients with critical or severe COVID-19 (24/33 patients; 72.72

ObjectiveHuman leptospirosis is a widespread zoonosis with endemic appearance in different parts of the world. Despite causing more than 1 million cases, nearly 60.000 deaths and 3 million disability-adjusted life-years per year, leptospirosis remains an underrecognized and neglected disease calling for multinational surveillance and international collaboration.MethodsThe leptospirosis registry LeptoScope is a novel project enabling both international and multi-disciplinary research on Leptospira-caused diseases. LeptoScope has an electronic case report form and can be assessed on the General Data Protection Regulation compliant platform clinicalsurveys.net. Due to its modular structure, LeptoScope depicts or hides items according to the documented case (e.g., patients treated in outpatient setting versus patient admitted to the intensive care unit). This ensures rapid, but standardized enrolment of patients even in epidemics.ResultsInformation collected in LeptoScope include demographics, pre-existing diseases, clinical presentation and measures in addition to outcome. A multinational research team from Germany, Belgium and Spain contributed a pilot cohort of 78 cases with Leptospira-associated diseases to confirm LeptoScope’s functionality and practicality.ConclusionLeptoScope is to our knowledge the first worldwide research platform on public health and clinical studies concerning Leptospira-associated diseases. LeptoScope promotes the needed collaboration at the cross-roads of public health, microbiology, infectious diseases and nephrology for an underrecognized and often neglected disease. Ensuring controlled or uncontrolled level II evidence LeptoScope may improve patient care and may provide evidence for robust treatment recommendations in future.

Wir stellen den Fall eines Reiserückkehrers mit letal verlaufendem Dengue-Schock-Syndrom vor. Ziel dieses Berichts ist es, die klinischen Auswirkungen dieser bei Reisenden sehr häufigen Krankheit zu veranschaulichen. Er verdeutlicht, dass sowohl primäre als auch sekundäre Dengueinfektionen zu schweren Verläufen und zum Tod führen können. Vor dem Hintergrund des Klimawandels ist in Zukunft mit einer Zunahme der Dengueinfektionen zu rechnen, insbesondere auch aus nichttropischen Ländern. Daher wird die Dengueimpfung als wirksame, primärpräventive Maßnahme weiterhin an Bedeutung hinzugewinnen.

ANCA-vasculitis (AAV) is a small-vessel vasculitis characterized by the presence of autoantibodies against proteinase-3 (PR3) or myeloperoxidase (MPO). The dynamics of the T-cell response within tissues is studied best in animal models. It was the aim to analyze the lesional T-cell dynamics in the experimental autoimmune vasculitis model. Female Wistar Kyoto-rats were immunized with human MPO emulsified in complete Freund's adjuvant. Control animals received complete Freund's adjuvant without MPO. Selected groups received anti-IL17A treatment. Lesional T-cells from kidneys were assessed by flow cytometry (FACS), realtime polymerase chain reaction (PCR) and EliSpot. All animals immunized with MPO developed signs of vasculitis. At week six, lung damage expressed as petechial bleeding score and renal damage quantified by albuminuria were highest. As analyzed by FACS, the fraction of renal Th17 cells peaked at week six in MPO rats equaling the proportion of Th1 cells. MPO-specific renal Th1 and Th17 cells were detectable by EliSpot at weeks four and six post-immunization in MPO-immunized rats being absent in control rats. Neutralization of IL-17A did not affect the development of humoral and cellular anti-MPO immunity. Likewise, pulmonary and renal vasculitis were not ameliorated. In summary, the dynamics of the lesional T-cell response in the EAV model shows a major participation of MPO-specific Th17 and Th1 cells in renal vasculitis. Simple cytokine neutralization was not efficacious in this disease model so that combined neutralization approaches should be studied further.

We present the case of a returning traveler with lethal dengue shock syndrome. The aim of this report is to illustrate the clinical impact of this disease, which is very common among travelers. It illustrates that both primary and secondary dengue infections can lead to severe courses and death. Against the background of climate change, an increase in dengue infections is to be expected in the future, especially from non-tropical countries. Dengue vaccination will therefore continue to gain in importance as an effective primary preventive measure.

BackgroundThanks to the great advance in antiretroviral therapy (ART), people living with HIV (PLWH) nowadays have a normal life expectancy. Due to chronic (subclinical) inflammation and long-term intake of potentially nephrotoxic medication, PLWH are at an elevated risk for CKD. Urinary Dickkopf 3 (uDKK3) acts as a noninvasive marker of renal tubular damage and predictor of progressive CKD. It has not been investigated in PLWH.MethodsThis observational study included 427 PLWH from the HIV outpatient clinic of the Department of Dermatology at the University Hospital Essen. We examined uDKK3-to-creatinine levels in PLWH with and without CKD. Renal function evolution was retrospectively assessed in order to investigate the relation between uDKK3 and CKD progression.ResultsUrinary DKK3-to-creatinine concentrations were significantly higher in PLWH with CKD and were associated with lower eGFR according to cystatin C (p = 0·009) and creatinine (p = 0·003). There was a trend towards higher uDKK3-to-creatinine concentrations in progressive CKD compared to non-progressive CKD, without reaching significance (OR 1·27; 95%-CI 0·33-2·08; p = 0·33).ConclusionsUrinary DKK3, a noninvasive marker, not only detects CKD in PLWH, but could also indicate its progression. This could help to identify PLWH with progressive CKD in need of effective treatment.

PURPOSE: The practice guideline for outpatient parenteral antimicrobial therapy (OPAT) aims to encourage broader adoption of OPAT into routine clinical practice in Germany. METHODS: The guideline was developed according to the guideline development framework by the Association of the Scientific Medical Societies (AWMF) in Germany. Literature search was conducted, and expert recommendations were formulated through consensus and published as an AWMF S1 guideline (expert group recommendations with consensus development in an informal process). RESULTS: OPAT is a safe and effective alternative to inpatient care for managing selected infectious diseases (ID) entities, which require intravenous antimicrobial therapy (AMT). ID specialists play a critical role in determining the indications for OPAT, the selection of suitable patients and the development of treatment plans. Specialist-led OPAT programs have been shown to enhance treatment efficacy, reduce hospital readmissions, and decrease healthcare costs. A structured, checklist-based approach is used to evaluate infection severity, available therapeutic options, patient comorbidities, and home care conditions. Adherence to antimicrobial stewardship (AMS) principles as well as regular clinical and laboratory monitoring are essential to ensure appropriate antimicrobial use and minimize adverse events, catheter-related complications and the risk of resistance. The selection of adequate vascular access is based on patient-specific factors, characteristics of the indicated antimicrobial and treatment duration, optimizing both safety and patient comfort. CONCLUSION: OPAT is a safe, cost-effective alternative to inpatient care, requiring specialists’ ID expertise and AMS. The guideline provides a framework for successful implementation in Germany.

Traditional cardiovascular risk scores underestimate the incidence of cardiovascular diseases (CVD) in people living with HIV (PLH). This study compared the effect of HIV-specific cardiovascular risk factors (CRF) with traditional CRF at baseline for their association with incident CVD in PLH. The ongoing, prospective HIV HEART Aging (HIVH) study assesses CVD in PLH in the German Ruhr Area since 2004. PLH from the HIVH study with at least 5 years of follow-up were examined with the help of Cox proportional hazards models using inverse probability-of-censoring weights. The models were adjusted for age and sex. The obtained hazard ratios (HR) and 95% confidence limits (CL) assessed the strength of the associations between CRF and CVD. One thousand two hundred forty-three individuals (male 1,040, female 203; mean age of 43 +/- 10 years) with 116 incident CVD events were analyzed. After adjusting for the traditional CRF, the HIV-specific CRF "a history of AIDS" and "higher age at diagnosis of HIV infection" (per 10 years) were associated with an increased CVD risk (HR 1.55, 95% CL: 1.05-2.28 and HR 1.55, 95% CL: 1.09-1.22, respectively). Higher CD4/CD8 ratio (per standard deviation), longer cumulative duration of antiretroviral therapies, and longer duration of HIV infection (per 10 years) showed indications for a decreased CVD risk (HR 0.75, 95% CL: 0.58-0.97, HR 0.71, 95% CL: 0.41-1.23, and HR 0.63, 95% CL: 0.44-0.90, respectively). Out of the traditional CRF, current smoking showed the strongest impact on CVD risk (HR 3.12, 95% CL: 2.06-4.74). In conclusion, HIV-specific factors, such as history of AIDS and CD4/CD8 ratio, were independently associated with an increased cardiovascular risk. Traditional CRF maintained a major effect on CVD. Clinical Trials Number (NCT04330287).

Introduction Granulomatosis due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium-intracellulare ( M. avium ) infection may trigger hypercalcemia. Here, we report a rare case of hypercalcemia and acute kidney damage related to IRIS in a person living with Human Immunodeficiency Virus (HIV). Case presentation A 39-year-old male person living with HIV presented with muscle weakness and unwanted weight loss of 8 kg within the last 2 weeks. Laboratory findings included serum hypercalcemia of 3.27 mmol/mL associated with elevated calcitriol and acute kidney damage. Since the first diagnosis of HIV and concomitant disseminated M. avium infection, the patient received antiretroviral therapy (ART), rifabutin, clarithromycin, and ethambutol. 18 Fluoro-D-glucose positron emission computed tomography ( 18 FDG-PET/CT) showed progressive multilocular lymphadenopathy. Biopsy specimen from the duodenum as well as retroperitoneal and mediastinal lymph nodes revealed granulomatous inflammation consistent with IRIS. Treatment with forced diuresis, bisphosphonates, and calcitonin normalized serum calcium and kidney function recovered. Conclusion Hypercalcemia due to IRIS is a rare differential diagnosis in persons living with HIV and may lead to acute kidney damage, despite sufficient ART and antimycobacterial treatment.

Background Data on impact of COVID‐19 vaccination and outcomes of patients with COVID‐19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. Methods and Results This was a retrospective analysis of patients with COVID‐19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID‐19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P =0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group ( P =0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome ( P =0.957). However, acute COVID‐19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007–1.417]; P =0.041). Conclusions Our study demonstrated no impact of COVID‐19 vaccination on angiographic or clinical outcome of COVID‐19–positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID‐19 was confirmed.

ObjectivesFarnesyltransferase 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.MethodsFor 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.ResultsThe 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.ConclusionFTI 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.

Introduction Immunosuppressive therapy is associated with an increased risk of severe courses of SARS-CoV-2 infection, with frequently delayed viral clearance. We report a case of an acute kidney transplant failure in persistent SARS-CoV-2 infection in a patient with absolute B-cell depletion after administration of rituximab for AB0-incompatible living donor kidney transplantation. Case presentation A 34-year-old unvaccinated patient is diagnosed with SARS-CoV-2 infection four months after kidney transplantation. With only mild symptoms and an estimated glomerular filtration rate (eGFR) of 44 ml/min/1.73 m 2 , therapy with molnupiravir was initially given. Within the next eight weeks, transplant biopsies were performed for acute graft failure. These showed acute T-cell rejection with severe acute tubular epithelial damage with only mild interstitial fibrosis and tubular atrophy (BANFF cat. 4 IB), and borderline rejection (BANFF cat. 3). A therapy with prednisolone and intravenous immunoglobulins was performed twice. With unchanged graft failure, the third biopsy also formally showed BANFF cat. 4 IB. However, fluorescence in situ hybridization detected SARS-CoV-2 viruses in large portions of the distal tubules. After nine weeks of persistent COVID-19 disease neither anti-SARS-CoV-2 IgG nor a SARS-CoV-2-specific cellular immune response could be detected, leading to the administration of sotrovimab and remdesivir. Among them, SARS-CoV-2 clearance, detection of IgG, and improvement of graft function were achieved. Conclusion Lack of viral clearance can lead to complications of SARS-CoV-2 infection with atypical manifestations. In kidney transplant patients, before initiating therapy, the differential diagnoses of “rejection” and “virus infection” should be weighed against each other in an interdisciplinary team of nephrologists, infectious diseases specialists and pathologists.

Cross-reactive cellular and humoral immunity can substantially contribute to antiviral defense against SARS-CoV-2 variants of concern (VOC). While the adult SARS-CoV-2 cellular and humoral immunity and its cross-recognition potential against VOC is broadly analyzed, similar data regarding the pediatric population are missing. In this study, we perform an analysis of the humoral and cellular SARS-CoV-2 response immune of 32 convalescent COVID-19 children (children), 27 convalescent vaccinated adults(C + V+) and 7 unvaccinated convalescent adults (C + V-). Similarly to adults, a significant reduction of cross-reactive neutralizing capacity against delta and omicron VOC was observed 6 months after SARS-CoV-2 infection. While SAR-CoV-2 neutralizing capacity was comparable among children and C + V- against all VOC, children demonstrated as expected an inferior humoral response when compared to C + V+. Nevertheless, children generated SARS-CoV-2 reactive T cells with broad cross-recognition potential. When compared to V + C+, children presented even comparable frequencies of WT-reactive CD4 + and CD8 + T cells with high avidity and functionality. Taking into consideration the limitations of study - unknown disease onset for 53% of the asymptomatic pediatric subjects, serological detection of SARS-CoV-2 infection-, our results suggest that following SARS-CoV-2 infection children generate a humoral SARS-CoV-2 response with neutralizing potential comparable to unvaccinated COVID-19 convalescent adults as well a sustained SARS-CoV-2 cellular response cross-reactive to VOC.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused millions of COVID-19 cases and deaths worldwide. Severity of pulmonary pathologies and poor prognosis were reported to be associated with the activation non-virus-specific bystander T cells. In addition, high concentrations of the macrophage migration inhibitory factor (MIF) were found in serum of COVID-19 patients. We hypothesized that these two pathogenic factors might be related and analyzed the expression of receptors for MIF on T cells in COVID-19. T cells from PBMCs of hospitalized patients with mild and severe COVID-19 were characterized. A significantly higher proportion of CD4+ and CD8+ T cells from COVID-19 patients expressed CD74 on the cell surface compared to healthy controls. To induce intracellular signaling upon MIF binding, CD74 forms complexes with CD44, CXCR2, or CXCR4. The vast majority of CD74+ T cells expressed CD44, whereas expression of CXCR2 and CXCR4 was low in controls but increased upon SARS-CoV-2 infection. Hence, T cells in COVID-19 patients express receptors that render them responsive to MIF. A detailed analysis of CD74+ T cell populations revealed that most of them had a central memory phenotype early in infection, while cells with an effector and effector memory phenotype arose later during infection. Furthermore, CD74+ T cells produced more cytotoxic molecules and proliferation markers. Our data provide new insights into the MIF receptor and co-receptor repertoire of bystander T cells in COVID-19 and uncovers a novel and potentially druggable aspect of the immunological footprint of SARS-CoV-2.

Background Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are increasingly observed in vaccinated individuals. Immune responses towards SARS-CoV-2 variants, particularly Omicron-BA.5, are poorly understood. We investigated the humoral and cellular immune responses of hospitalized COVID-19 patients during Delta and Omicron infection waves. Methods The corresponding SARS-CoV-2 variant of the respective patients were identified by whole genome sequencing. Humoral immune responses were analyzed by ELISA and a cell culture-based neutralization assay against SARS-CoV-2 D614G isolate (wildtype), Alpha, Delta (AY.43) and Omicron (BA.1 and BA.5). Cellular immunity was evaluated with an IFN-γ ELISpot assay. Results On a cellular level, patients showed a minor IFN-γ response after stimulating PBMCs with mutated regions of SARS-CoV-2 variants. Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced. Double-vaccinated patients with Delta breakthrough infection showed a significantly increased neutralizing antibody response against Delta compared to double-vaccinated uninfected controls (median complete neutralization titer (NT 100 ) 640 versus 80, p<0.05). Omicron-BA.1 infection increased neutralization titers against BA.1 in double-vaccinated patients (median NT 100 of 160 in patients versus 20 in controls, p=0.07) and patients that received booster vaccination (median NT 100 of 50 in patients versus 20 in controls, p=0.68). For boosted patients with BA.5 breakthrough infection, we found no enhancing effect on humoral immunity against SARS-CoV-2 variants. Conclusion Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced in SARS-CoV-2 breakthrough infections. Delta and Omicron-BA.1 but not Omicron-BA.5 infections boosted the humoral immunity in double-vaccinated patients and patients with booster vaccination. Despite BA.5 breakthrough infection, those patients may still be vulnerable for reinfections with BA.5 or other newly emerging variants of concern.

Background: A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce. Methods: In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation. A detailed medical history, blood and instrumental tests and physical examination were obtained from all patients. SARS-CoV-2 reactive T cell response was analyzed via multiparametric flowcytometry and the humoral immunity was addressed via pseudovirus neutralization and ELISA assay. Results: The most common PASC symptoms were shortness of breath/exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache and lack of concentration. Blood count and clinical chemistry showed no statistical differences among the study groups. We detected higher frequencies of spike (S) reactive CD4+ and CD8+ T cells among the PASC study group, characterized by TNFα and IFNγ production and low functional avidity. CRP levels are positively correlated with IFNγ producing reactive CD8+ T cells. Conclusions: Our data might indicate a possible involvement of a persistent cellular inflammatory response triggered by SARS-CoV-2 in the development of the observed sequelae in pediatric PASC. These results may have implications on future therapeutic and prevention strategies.

Abstract Background and Aims The pathophysiology of rejection after renal transplantation (RTx) has not been unraveled completely. In previous studies, Th17 cells were shown to be involved in several autoimmune diseases affecting the kidney, e.g. lupus nephritis, glomerulonephritis and ANCA vasculitis. The aim of this study was to decipher the dynamics of rejection after RTx with focus on the Th17 cells and IL17 cytokine family. Method For this purpose, the established Fischer to Lewis rat RTx model was used. In this model, renal rejection is elicited and develops over time. The donor renal grafts were harvested from Fischer rats and exposed to static cold storage using HTK or UW buffer. The Lewis recipients were treated for 10 days post-transplant with ciclosporin A and then immunosuppressive therapy stopped. Recipients were harvested early (2 hours, 30 days) and late after RTx (12 weeks, 28 weeks). To analyze the dynamics of inflammation, kidney sections were stained for CD3+ (T-cells) and MPO (neutrophils). RT-PCR was used to detect cytokine gene expression of several target genes within the renal grafts. IL17A Elispot was established to analyse circulating Th17 cells in the recipients. Results Generally, the cold ischemia time of the renal allograft was associated with the lifetime of the recipients. Furthermore, with increasing cold ischemia time of the graft, intra-renal CD3+ T-cell infiltration was enhanced. An increased CD3+ and a diminished number of MPO+ neutrophils were detected in the renal grafts late after RTx compared to early timepoints. Moreover, the intra-graft IL17C gene expression was enhanced late after renal transplantation while CXCL1 and CXCL2 were upregulated early after renal transplantation. IL17A gene expression reached higher levels than IFNg in later timepoints e.g. 30 days, while in early stages IL17A was below IFNg. The impact of cold storage buffer on the immunogenicity of the renal transplant was investigated, too. The use of UW led to a higher intra-renal CD3+ T-cell infiltration at later timepoints compared with HTK. In early stages after transplantation, higher levels of intra-renal MPO+ neutrophils were found upon cold storage using UW compared to cold storage using HTK. Conclusion The inflammatory process during chronic kidney rejection is T-cell driven and may involve the IL17C cascade. The early phase is dominated by neutrophils with enhanced intra-renal expression of CXCL1 and CXCL2. Furthermore, the polarization of the T-cell driven immune response may change depending on the time point after transplantation.

We present the case of a 24-year-old male with CNS granulomatosis due to an immunodeficiency syndrome which was identified as deficiency of adenosine deaminase 2 (DADA2) as a cause of brainstem infarction. Case report and detailed description of the clinical course of diagnosis and treatment. The patient’s medical history consisted of an unknown immunodeficiency syndrome. Based on former findings, common variable immunodeficiency (CVID) was diagnosed. The patient suffered from three consecutive brainstem strokes of unknown etiology within 3 years. An MRI scan detected gadolinium-enhancing, granulomatous-suspect lesions in the interpeduncular cistern, temporal lobe, and tegmentum. Laboratory analysis was compatible with CVID, with leukopenia and immunoglobulin deficiency. Because granulomatous CNS inflammation was suspected, the patient received methylprednisolone immunosuppressive therapy, which led to partially regressive MRI lesions. However, in contrast to imaging, the patient showed a progressive cerebellar syndrome, indicating plasma exchange therapy and immunoglobulin treatment, which led to rapid symptom amelioration. After a relapse and a further stroke, expanded analysis confirmed DADA2 (and not CVID) as the inflammatory cause for recurrent stroke. After starting the therapy with immunoglobulins and adalimumab, no further strokes occurred. We present the case of a young adult with diagnosis of DADA2 as a cause for recurrent strokes due to vasculitis. This stroke etiology is rare but should be considered as a cause of recurrent stroke of unknown origin in young patients to avoid a disabling disease course by disease-specific treatment options.