A group of the Centre for indivualized medicine [CiiM]

News

head of the work group: Prof. Li

Recent Submissions

  • Case Report: Convalescent Plasma Therapy Induced Anti-SARS-CoV-2 T Cell Expansion, NK Cell Maturation and Virus Clearance in a B Cell Deficient Patient After CD19 CAR T Cell Therapy.

    Bošnjak, Berislav; Odak, Ivan; Ritter, Christiane; Stahl, Klaus; Graalmann, Theresa; Steinbrück, Lars; Blasczyk, Rainer; Falk, Christine S; Schulz, Thomas F; Wedemeyer, Hans Heinrich; et al. (Frontiers, 2021-08-12)
    Here, we described the case of a B cell-deficient patient after CD19 CAR-T cell therapy for refractory B cell Non-Hodgkin Lymphoma with protracted coronavirus disease 2019 (COVID-19). For weeks, this patient only inefficiently contained the virus while convalescent plasma transfusion correlated with virus clearance. Interestingly, following convalescent plasma therapy natural killer cells matured and virus-specific T cells expanded, presumably allowing virus clearance and recovery from the disease. Our findings, thus, suggest that convalescent plasma therapy can activate cellular immune responses to clear SARS-CoV-2 infections. If confirmed in larger clinical studies, these data could be of general importance for the treatment of COVID-19 patients.
  • Structural basis of the complete poxvirus transcription initiation process.

    Grimm, Clemens; Bartuli, Julia; Boettcher, Bettina; Szalay, Aladar A; Fischer, Utz; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. (Nature reseach, 2021-09-23)
    Poxviruses express their genes in the cytoplasm of infected cells using a virus-encoded multi-subunit polymerase (vRNAP) and unique transcription factors. We present cryo-EM structures that uncover the complete transcription initiation phase of the poxvirus vaccinia. In the pre-initiation complex, the heterodimeric early transcription factor VETFs/l adopts an arc-like shape spanning the polymerase cleft and anchoring upstream and downstream promoter elements. VETFI emerges as a TBP-like protein that inserts asymmetrically into the DNA major groove, triggers DNA melting, ensures promoter recognition and enforces transcription directionality. The helicase VETFs fosters promoter melting and the phospho-peptide domain (PPD) of vRNAP subunit Rpo30 enables transcription initiation. An unprecedented upstream promoter scrunching mechanism assisted by the helicase NPH-I probably fosters promoter escape and transition into elongation. Our structures shed light on unique mechanisms of poxviral gene expression and aid the understanding of thus far unexplained universal principles in transcription.
  • Complete Genome Sequencing of Leptospira interrogans Isolates from Malaysia Reveals Massive Genome Rearrangement but High Conservation of Virulence-Associated Genes

    Ramli, Siti Roszilawati; Bunk, Boyke; Spröer, Cathrin; Geffers, Robert; Jarek, Michael; Bhuju, Sabin; Goris, Marga; Mustakim, Sahlawati; Pessler, Frank; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover, Germany. (MDPI, 2021-09-15)
    The ability of Leptospirae to persist in environments and animal hosts but to cause clinically highly variable disease in humans has made leptospirosis the most common zoonotic disease. Considering the paucity of data on variation in complete genomes of human pathogenic Leptospirae, we have used a combination of Single Molecule Real-Time (SMRT) and Illumina sequencing to obtain complete genome sequences of six human clinical L. interrogans isolates from Malaysia. All six contained the larger (4.28-4.56 Mb) and smaller (0.34-0.395 Mb) chromosome typical of human pathogenic Leptospirae and 0-7 plasmids. Only 24% of the plasmid sequences could be matched to databases. We identified a chromosomal core genome of 3318 coding sequences and strain-specific accessory genomes of 49-179 coding sequences. These sequences enabled detailed genomic strain typing (Genome BLAST Distance Phylogeny, DNA-DNA hybridization, and multi locus sequence typing) and phylogenetic classification (whole-genome SNP genotyping). Even though there was some shared synteny and collinearity across the six genomes, there was evidence of major genome rearrangement, likely driven by horizontal gene transfer and homologous recombination. Mobile genetic elements were identified in all strains in highly varying numbers, including in the rfb locus, which defines serogroups and contributes to immune escape and pathogenesis. On the other hand, there was high conservation of virulence-associated genes including those relating to sialic acid, alginate, and lipid A biosynthesis. These findings suggest (i) that the antigenic variation, adaption to various host environments, and broad spectrum of virulence of L. interrogans are in part due to a high degree of genomic plasticity and (ii) that human pathogenic strains maintain a core set of genes required for virulence.
  • Evolution of cytokine production capacity in ancient and modern European populations.

    Domínguez-Andrés, Jorge; Kuijpers, Yunus; Bakker, Olivier B; Jaeger, Martin; Xu, Cheng-Jian; Van der Meer, Jos Wm; Jakobsson, Mattias; Bertranpetit, Jaume; Joosten, Leo Ab; Li, Yang; et al. (eLife Sciences Publications, 2021-09-07)
    As our ancestors migrated throughout different continents, natural selection increased the presence of alleles advantageous in the new environments. Heritable variations that alter the susceptibility to diseases vary with the historical period, the virulence of the infections, and their geographical spread. In this study we built polygenic scores for heritable traits that influence the genetic adaptation in the production of cytokines and immune-mediated disorders, including infectious, inflammatory, and autoimmune diseases, and applied them to the genomes of several ancient European populations. We observed that the advent of the Neolithic was a turning point for immune-mediated traits in Europeans, favoring those alleles linked with the development of tolerance against intracellular pathogens and promoting inflammatory responses against extracellular microbes. These evolutionary patterns are also associated with an increased presence of traits related to inflammatory and auto-immune diseases.
  • Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination.

    Barros-Martins, Joana; Hammerschmidt, Swantje I; Cossmann, Anne; Odak, Ivan; Stankov, Metodi V; Morillas Ramos, Gema; Dopfer-Jablonka, Alexandra; Heidemann, Annika; Ritter, Christiane; Friedrichsen, Michaela; et al. (Nature, 2021-07-14)
    Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca's ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of already ChAd-primed individuals with the decision to receive either a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School's COVID-19 Contact Study cohort of healthcare professionals to monitor ChAd-primed immune responses before and 3 weeks after booster with ChAd (n = 32) or BioNTech/Pfizer's BNT162b2 (n = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4+ and CD8+ T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants of concern of severe acute respiratory syndrome coronavirus 2.
  • Different rates of pollen and seed gene flow cause branch-length and geographic cytonuclear discordance within Asian butternuts.

    Xu, Lin-Lin; Yu, Rui-Min; Lin, Xin-Rui; Zhang, Bo-Wen; Li, Nan; Lin, Kui; Zhang, Da-Yong; Bai, Wei-Ning; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. (Wiley, 2021-07-13)
    opological cytonuclear discordance is commonly observed in plant phylogenetic and phylogeographic studies, yet few studies have attempted to detect two other forms of cytonuclear discordance (branch length and geographical) and to uncover the causes of the discordance. We used the whole nuclear and chloroplast genome data from 80 individual Asian butternuts to reveal the pattern and processes of cytonuclear discordance. Our findings indicate that the chloroplast genome had substantially deeper divergence (branch-length discordance) and a steeper cline in the contact zone (geographic discordance) compared with the nuclear genome. After various hypothesis have been tested, the results suggest that incomplete lineage sorting, positive selection and cytonuclear incompatibility are probably insufficient to explain this pattern. However, isolation-by-distance analysis and gene flow estimation point to a much higher level of gene flow by pollen compared with by seeds, which may have slowed down lineage divergence and mediated wider contact for nuclear genome compared with the chloroplast genome. Altogether, this study highlights a critical role of sex-biased dispersal in causing discordance between the nuclear and plastid genome of Asian butternuts. Given its ubiquity among plants, asymmetric gene flow should be given a high priority in future studies of cytonuclear discordance.
  • The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men.

    Kilic, Gizem; Bulut, Ozlem; Jaeger, Martin; Ter Horst, Rob; Koeken, Valerie A C M; Moorlag, Simone J C F M; Mourits, Vera P; de Bree, Charlotte; Domínguez-Andrés, Jorge; Joosten, Leo A B; et al. (Frontiers, 2021-08-09)
    Male sex and old age are risk factors for COVID-19 severity, but the underlying causes are unknown. A possible explanation for this might be the differences in immunological profiles in males and the elderly before the infection. With this in mind, we analyzed the abundance of circulating proteins and immune populations associated with severe COVID-19 in 2 healthy cohorts. Besides, given the seasonal profile of COVID-19, the seasonal response against SARS-CoV-2 could also be different in the elderly and males. Therefore, PBMCs of female, male, young, and old subjects in different seasons of the year were stimulated with heat-inactivated SARS-CoV-2 to investigate the season-dependent anti-SARS-CoV-2 immune response. We found that several T cell subsets, which are known to be depleted in severe COVID-19 patients, were intrinsically less abundant in men and older individuals. Plasma proteins increasing with disease severity, including HGF, IL-8, and MCP-1, were more abundant in the elderly and males. Upon in vitro SARS-CoV-2 stimulation, the elderly produced significantly more IL-1RA and had a dysregulated IFNγ response with lower production in the fall compared with young individuals. Our results suggest that the immune characteristics of severe COVID-19, described by a differential abundance of immune cells and circulating inflammatory proteins, are intrinsically present in healthy men and the elderly. This might explain the susceptibility of men and the elderly to SARS-CoV-2 infection.
  • HBV-RNA Co-amplification May Influence HBV DNA Viral Load Determination.

    Maasoumy, Benjamin; Geretti, Anna Maria; Frontzek, André; Austin, Harrison; Aretzweiler, Gudrun; Garcia-Álvarez, Monica; Leuchter, Susanne; Simon, Christian O; Marins, Ed G; Canchola, Jesse A; et al. (Wiley, 2020-05-26)
    Despite effective hepatitis B virus (HBV)-DNA suppression, HBV RNA can circulate in patients receiving nucleoside/nucleotide analogues (NAs). Current assays quantify HBV DNA by either real-time polymerase chain reaction (PCR), which uses DNA polymerase, or transcription-mediated amplification, which uses reverse-transcriptase (RT) and RNA polymerase. We assessed the effect of RT capability on HBV-DNA quantification in samples from three cohorts, including patients with quantified HBV RNA. We compared the HBV-DNA levels by real-time PCR (cobas HBV, Roche 6800/8800; Xpert HBV, Cepheid), transcription-mediated amplification (Aptima HBV, Hologic), and real-time PCR with added RT capability (cobas HBV+RT). In the first cohort (n = 45) followed over 192 weeks of NA therapy, on-treatment HBV-DNA levels were higher with cobas HBV+RT than cobas HBV (mean difference: 0.14 log10 IU/mL). In a second cohort (n = 50) followed over 96 weeks of NA therapy, HBV-DNA viral load was significantly higher with the cobas HBV+RT and Aptima HBV compared with the cobas HBV test at all time points after initiation of NA therapy (mean difference: 0.65-1.16 log10 IU/mL). A clinically significant difference was not detected between the assays at baseline. In a third cohort (n = 53), after a median of 2.2 years of NA therapy, we detected HBV RNA (median 5.6 log10 copies/mL) in 23 patients (43.4%). Median HBV-DNA levels by Aptima HBV were 2.4 versus less than 1 log10 IU/mL in samples with HBV RNA and without HBV RNA, respectively (P = 0.0006). In treated patients with HBV RNA, Aptima HBV measured higher HBV-DNA levels than Xpert HBV and cobas HBV. Conclusion: Tests including an RT step may overestimate HBV DNA, particularly in samples with low viral loads as a result of NA therapy. This overestimation is likely due to amplification of HBV RNA and may have an impact on clinical decisions.
  • Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on haemodialysis.

    Strengert, Monika; Becker, Matthias; Ramos, Gema Morillas; Dulovic, Alex; Gruber, Jens; Juengling, Jennifer; Lürken, Karsten; Beigel, Andrea; Wrenger, Eike; Lonnemann, Gerhard; et al. (Elsevier, 2021-08-12)
    Background: Patients with chronic renal insufficiency on maintenance haemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only a few studies have addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population. Methods: We assessed immunogenicity of the mRNA vaccine BNT162b2 in at-risk dialysis patients and characterised systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants Alpha, Beta, Epsilon and Cluster 5 by ACE2-RBD competition assay. Findings: Patients on maintenance haemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to a vaccinated non-dialysed control population. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished. Interpretation: Quantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on maintenance haemodialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in the face of emerging variants of concern may favour this at-risk population for re-vaccination using modified vaccines at the earliest opportunity. Funding: Initiative and Networking Fund of the Helmholtz Association of German Research Centres, EU Horizon 2020 research and innovation program, State Ministry of Baden-Württemberg for Economic Affairs, Labour and Tourism.
  • Antimicrobial resistance in patients with decompensated liver cirrhosis and bacterial infections in a tertiary center in Northern Germany.

    Hillert, Annika; Schultalbers, Marie; Tergast, Tammo L; Vonberg, Ralf-Peter; Rademacher, Jessica; Wedemeyer, Heiner; Cornberg, Markus; Ziesing, Stefan; Maasoumy, Benjamin; Höner Zu Siederdissen, Christoph; et al. (BMC, 2021-07-20)
    Background and aims: Bacterial infections are common in patients with decompensated liver cirrhosis and a leading cause of death. Reliable data on antibiotic resistance are required to initiate effective empiric therapy. We here aim to assess the antimicrobial resistance profile of bacteria among patients with liver cirrhosis and infection. Methods: Overall, 666 cirrhotic patients admitted to Hannover Medical School between January 2012 and April 2018 with ascites were assessed for bacterial infection. In case of infection, bacteria cultured from microbiological specimens of ascites, blood or urine were identified and analyzed for resistances against common antibiotic agents. Furthermore, analyses compared two periods of time and community-acquired vs. nosocomial infections. Results: In 281 patients with infection, microbiological sampling was performed and culture-positive results were obtained in 56.9%. Multidrug-resistant (MDR)-bacteria were found in 54 patients (19.2%). Gram-positive organisms were more common (n = 141/261, 54.0%) and detected in 116/192 culture-positive infections (60.4%). Comparing infections before and after 2015, a numerical decline for MDR-bacteria (23.8% vs. 15.6%, p = 0.08) was observed with a significant decline in meropenem resistance (34.9% vs. 19.5%, p = 0.03). MDR-bacteria were more frequent in the case of nosocomial infections. Of note, in ascites the majority of the tested bacteria were resistant against ceftriaxone (73.8%) whereas significantly less were resistant against meropenem (27.0%) and vancomycin (25.9%). Conclusions: In our tertiary center, distinct ratios of gram-positive infection with overall low ratios of MDR-bacteria were found. Adequate gram-positive coverage in the empiric therapy should be considered. Carbapenem treatment may be omitted even in nosocomial infection. In contrast, 3rd generation cephalosporins cannot be recommended even in community-acquired infection in our cirrhotic population.
  • The role of sirtuin 1 on the induction of trained immunity.

    Mourits, Vera P; Helder, Leonie S; Matzaraki, Vasiliki; Koeken, Valerie A C M; Groh, Laszlo; de Bree, L Charlotte J; Moorlag, Simone J C F M; van der Heijden, Charlotte D C C; Keating, Samuel T; van Puffelen, Jelmer H; et al. (Elsevier, 2021-06-12)
    Sirtuin 1 (SIRT1) has been described to modify immune responses by modulation of gene transcription. As transcriptional reprogramming is the molecular substrate of trained immunity, a de facto innate immune memory, we investigated the role of SIRT1 in the induction of trained immunity. We identified various SIRT1 genetic single nucleotide polymorphisms affecting innate and adaptive cytokine production of human peripheral blood mononuclear cells (PBMCs) in response to various stimuli on the one hand, and in vitro induction of trained immunity on the other hand. Furthermore, inhibition of SIRT1 upregulated pro-inflammatory innate cytokine production upon stimulation of PBMCs. However, inhibition of SIRT1 in vitro had no effect on cytokine responses upon induction of trained immunity, while activation of SIRT1 mildly modified trained immunity responses. In conclusion, SIRT1 modifies innate cytokine production by PBMCs in response to various microbes, but has only a secondary role for BCG and β-glucan-induced trained immunity responses.
  • Controlling inflammation in the elderly with BCG vaccination.

    Koeken, Valerie A C M; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. (AAAS, 2021-08-04)
    The tuberculosis vaccine BCG may protect against inflammation in the elderly as well as offer an option for protection from SARS-CoV-2 in developing countries.
  • Reaching the Unreachable: Strategies for HCV Eradication in Patients With Refractory Opioid Addiction-A Real-world Experience.

    Sandmann, Lisa; Deppe, Julian; Beier, Christoph; Ohlendorf, Valerie; Schneider, Julia; Wedemeyer, Heiner; Wedegärtner, Felix; Cornberg, Markus; Maasoumy, Benjamin; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. (2021-06-17)
  • S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion – (AWMF-Register-Nr. 021-11)

    Cornberg, Markus; Sandmann, Lisa; Protzer, Ulrike; Niederau, Claus; Tacke, Frank; Berg, Thomas; Glebe, Dieter; Jilg, Wolfgang; Wedemeyer, Heiner; Wirth, Stefan; et al. (Thieme, 2021-07-12)
    [No abstract available]
  • Leitlinienreport zur aktualisierten S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion

    Jansen, Petra Lynen; van Leeuwen, Pia; Sandmann, Lisa; Cornberg, Markus; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. (Thieme, 2021-07-12)
    [No abstract available]
  • Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease.

    Chu, Xiaojing; Jaeger, Martin; Beumer, Joep; Bakker, Olivier B; Aguirre-Gamboa, Raul; Oosting, Marije; Smeekens, Sanne P; Moorlag, Simone; Mourits, Vera P; Koeken, Valerie A C M; et al. (BMC, 2021-07-06)
    Background: Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors. Result: We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation. We also examine the genetic regulation of metabolites associated with immune phenotypes through genome-wide association analysis and identify 29 significant loci, including eight novel independent loci. Of these, one locus (rs174584-FADS2) associated with arachidonic acid metabolism is causally associated with Crohn's disease, suggesting it is a potential therapeutic target. Conclusion: This study provides a comprehensive map of the integration between the blood metabolome and immune phenotypes, reveals novel genetic factors that regulate blood metabolite concentrations, and proposes an integrative approach for identifying new disease treatment targets.
  • Significant compartment-specific impact of different RNA extraction methods and PCR assays on the sensitivity of hepatitis E virus detection.

    Behrendt, Patrick; Bremer, Birgit; Todt, Daniel; Steinmann, Eike; Manns, Michael Peter; Cornberg, Markus; Wedemeyer, Heiner; Maasoumy, Benjamin; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. (Wiley, 2021-03-22)
    We determined the limit of detection of the RealStar HEV RT-PCR V2.0 Kit (altona Diagnostics, RS) utilizing 3 RNA extraction methods (COBAS® AmpliPrep Total Nucleic Acid Isolation Kit, TNAi Roche; MagNA Pure 96 DNA, Viral NA SV Kit, MgP; QIAamp Viral RNA mini Kit Qiagen; VRK) in plasma and stool. The most sensitive method was evaluated in a total of 307 longitudinal samples of patients with HEV infection (acute = 18/chronic = 36) and compared to results with the former diagnostic standard of our centre (TNAi/FastTrack Diagnostic; FTD).
  • Multi-Omics Approaches in Immunological Research.

    Chu, Xiaojing; Zhang, Bowen; Koeken, Valerie A C M; Gupta, Manoj Kumar; Li, Yang; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. (2021-06-11)
    The immune system plays a vital role in health and disease, and is regulated through a complex interactive network of many different immune cells and mediators. To understand the complexity of the immune system, we propose to apply a multi-omics approach in immunological research. This review provides a complete overview of available methodological approaches for the different omics data layers relevant for immunological research, including genetics, epigenetics, transcriptomics, proteomics, metabolomics, and cellomics. Thereafter, we describe the various methods for data analysis as well as how to integrate different layers of omics data. Finally, we discuss the possible applications of multi-omics studies and opportunities they provide for understanding the complex regulatory networks as well as immune variation in various immune-related diseases.
  • Distinct Immune Imprints of Post-Liver Transplantation Hepatitis C Persist Despite Viral Clearance.

    Aregay, Amare; Engel, Bastian; Port, Kerstin; Vondran, Florian W R; Bremer, Birgit; Niehaus, Christian; Khera, Tanvi; Richter, Nicolas; Jaeckel, Elmar; Cornberg, Markus; et al. (Wiley, 2021-02-28)
    Recurrence or de novo infection of hepatitis C virus (HCV) after liver transplantation (LT) has been associated with progressive graft hepatitis that can be improved by treatment with novel direct-acting antivirals. Cases of rejection episodes have been described during and after HCV treatment. The evolution of innate and adaptive immune response during and after cure of HCV LT is unknown. We studied 74 protein biomarkers in the plasma of LT patients receiving antiviral therapy. In addition, deep immune phenotyping of both the myeloid and lymphoid immune cell subsets in peripheral blood mononuclear cells was performed. We found that LT patients with active HCV infection displayed distinct alterations of inflammatory protein biomarkers, such as C-X-Cmotif chemokine 10 (CXCL10), caspase 8, C-C motif chemokine 20 (CCL20), CCL19, interferon γ, CUB domain-containing protein 1 (CDCP1), interleukin (IL)-18R1, CXCL11, CCL3, IL8, IL12B, tumor necrosis factor-beta, CXCL6, osteoprotegerin, IL10, fms-related tyrosine kinase 3 ligand, hepatocyte growth factor, urokinase-type plasminogen activator, neurotrophin-3, CCL4, IL6, tumornecrosis factor receptor superfamily member 9, programmed death ligand 1, IL18, and monocyte chemotactic protein 1, and enrichment of peripheral immune cell subsets unlike patients without HCV infection who received transplants. Interestingly, patients who cleared HCV after LT did not normalize the altered inflammatory milieu nor did the peripheral immune cell subsets normalize to what would be seen in the absence of HCV recurrence. Overall, these data indicate that HCV-specific imprints on inflammatory analytes and immune cell subsets after LT are not completely normalized by therapy-induced HCV elimination. This is in line with the clinical observation that cure of HCV after LT did not trigger rejection episodes in many patients.
  • Protected or not protected, that is the question - First data on COVID-19 vaccine responses in patients with NAFLD and liver transplant recipients.

    Eberhardt, Christiane S; Cornberg, Markus; CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. (2021-05-25)
    [no abstract available]

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