Espen Melum

• Gregersen, Ida; Kong, Xiang Yi; Kooijman, Sander; Foyn, Håvard; Grannes, Helene & Olsen, Maria Belland [Show all 25 contributors for this article] (2024). T cells with increased responsiveness cause obesity in mice without diet intervention. iScience. ISSN 2589-0042. 27(4). doi: 10.1016/j.isci.2024.109471.
• Nikitina, Darja; Lukosevicius, Rokas; Tilinde, Deimante; Muskieta, Tomas; Hov, Johannes Espolin Roksund & Melum, Espen [Show all 11 contributors for this article] (2024). Cell-Free Microbial DNA Analysis: Effects of Blood Plasma and Serum Quantity, Biobanking Protocols, and Isolation Kits. Biopreservation and Biobanking. ISSN 1947-5535. doi: 10.1089/bio.2023.0048.
• Jiang, Xiaojun; Otterdal, Kari; Chung, Brian K.; Maucourant, Christopher; Rønneberg, Jørgen Dybevik & Zimmer, Christine L [Show all 14 contributors for this article] (2023). Cholangiocytes Modulate CD100 Expression in the Liver and Facilitate Pathogenic T-Helper 17 Cell Differentiation. Gastroenterology. ISSN 0016-5085. doi: 10.1053/j.gastro.2023.11.283. Full text in Research Archive
• Oldereid, Tine Simensen; Jiang, Xiaojun; Øgaard, Jonas Daniel Sjøberg; Schrumpf, Elisabeth; Bjørnholt, Jørgen & Rasmussen, Henrik [Show all 7 contributors for this article] (2023). Microbial exposure during early life regulates development of bile duct inflammation. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 59(2), p. 192–201. doi: 10.1080/00365521.2023.2278423. Full text in Research Archive
• Oldereid, Tine Simensen; Jiang, Xiaojun; Nordhus, Kathrine Sivertsen; Ponzetta, Andrea; Bjørnholt, Jørgen & Björkström, Niklas K. [Show all 8 contributors for this article] (2023). Role of bacteria and microbial metabolites in immune modulation during early life. Scandinavian Journal of Immunology. ISSN 0300-9475. doi: 10.1111/sji.13336. Full text in Research Archive
• Harrison, Sean Philip; Siller, Richard; Tanaka, Yoshiaki; Chollet Dugarte, Maria Eugenia; de la Morena-Barrio, María Eugenia & Xiang, Yangfei [Show all 36 contributors for this article] (2023). Scalable production of tissue-like vascularized liver organoids from human PSCs. Experimental and Molecular Medicine. ISSN 1226-3613. 55, p. 2005–2024. doi: 10.1038/s12276-023-01074-1. Full text in Research Archive
• Braadland, Peder Rustøen; Bergquist, Annika; Kummen, Martin; Bossen, Lars; Engesæter, Lise Katrine & Reims, Henrik Mikael [Show all 21 contributors for this article] (2023). Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation. Journal of Hepatology. ISSN 0168-8278. 79(4), p. 955–966. doi: 10.1016/j.jhep.2023.05.038. Full text in Research Archive
• Andersen, Ina Marie; Reims, Henrik Mikael; Grzyb, Krzysztof; Fevang, Børre; Melum, Espen & Aukrust, Pål [Show all 10 contributors for this article] (2023). Long-term survival after liver transplantation in patients with common variable immunodeficiency. Liver transplantation. ISSN 1527-6465. 29(8), p. 894–899. doi: 10.1097/LVT.0000000000000130.
• Bergsmark, Thomas; Engesæter, Lise Katrine; Rasmussen, Allan; Bennet, William; Nordin, Arno & Pall, Virge [Show all 9 contributors for this article] (2023). Long-term survival after liver transplantation for alcohol-related liver disease in the Nordic countries. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 58(8), p. 923–930. doi: 10.1080/00365521.2023.2184193.
• Brevini, Teresa; Maes, Mailis; Webb, Gwilym J; John, Binu V; Fuchs, Claudia Daniela & Buescher, Gustav [Show all 42 contributors for this article] (2022). FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature. ISSN 0028-0836. doi: 10.1038/s41586-022-05594-0. Full text in Research Archive
• Busek, Mathias; Aizenshtadt, Aleksandra; Koch, Timo; Frank, Anna; Delon, Ludivine Sylvie Claude & Amirola Martinez, Mikel [Show all 12 contributors for this article] (2022). Pump-less, recirculating organ-on-a-chip (rOoC) platform . Lab on a Chip. ISSN 1473-0197. p. 345–361. doi: 10.1039/d2lc00919f. Full text in Research Archive
• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Show all 40 contributors for this article] (2022). Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants. npj Vaccines. ISSN 2059-0105. 7(1). doi: 10.1038/s41541-022-00586-7. Full text in Research Archive
• Chung, Brian K.; Øgaard, Jonas; Reims, Henrik Mikael; Karlsen, Tom Hemming & Melum, Espen (2022). Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis. Hepatology communications.. ISSN 2471-254X. 6(9), p. 2538–2550. doi: 10.1002/hep4.2001. Show summary

  Liver fibrosis and cirrhosis have limited therapeutic options and represent a serious unmet patient need. Recent use of single-cell RNA sequencing (scRNAseq) has identified enriched cell types infiltrating cirrhotic livers but without defining the microanatomical location of these lineages thoroughly. To assess whether fibrotic liver regions specifically harbor enriched cell types, we explored whether whole-tissue spatial transcriptomics combined with scRNAseq and gene deconvolution analysis could be used to localize cell types in cirrhotic explants of patients with end-stage liver disease (total n = 8; primary sclerosing cholangitis, n = 4; primary biliary cholangitis, n = 2, alcohol-related liver disease, n = 2). Spatial transcriptomics clearly identified tissue areas of distinct gene expression that strongly correlated with the total area (Spearman r = 0.97, p = 0.0004) and precise location (parenchyma, 87.9% mean congruency; range, 73.1%–97.1%; fibrosis, 68.5% mean congruency; range, 41.0%–91.7%) of liver regions classified as parenchymal or fibrotic by conventional histology. Deconvolution and enumeration of parenchymal and fibrotic gene content as measured by spatial transcriptomics into distinct cell states revealed significantly higher frequencies of ACTA2+ FABP4+ and COL3A1+ mesenchymal cells, IL17RA+ S100A8+ and FCER1G+ tissue monocytes, VCAM1+ SDC3+ Kupffer cells, CCL4+ CCL5+ KLRB1+ and GZMA+ IL17RA+ T cells and HLA-DR+, CD37+ CXCR4+ and IGHM+ IGHG+ B cells in fibrotic liver regions compared with parenchymal areas of cirrhotic explants. Conclusion: Our findings indicate that spatial transcriptomes of parenchymal and fibrotic liver regions express unique gene content within cirrhotic liver and demonstrate proof of concept that spatial transcriptomes combined with additional RNA sequencing methodologies can refine the localization of gene content and cell lineages in the search for antifibrotic targets.

• Valestrand, Laura Cecilie; Zheng, Fei; Hansen, Simen Hyll; Øgaard, Jonas; Hov, Johannes Espolin Roksund & Björkström, Niklas K. [Show all 9 contributors for this article] (2022). Bile from Patients with Primary Sclerosing Cholangitis Contains Mucosal-Associated Invariant T-Cell Antigens. American Journal of Pathology. ISSN 0002-9440. 192(4), p. 629–641. doi: 10.1016/j.ajpath.2021.12.008. Full text in Research Archive Show summary

  Primary sclerosing cholangitis (PSC) is associated with altered microbiota of the gut and bile. Mucosal-associated invariant T (MAIT) cells, enriched in human liver, uniquely recognize microbial-derived metabolites. This study aimed to determine whether bile from patients with PSC contains antigens activating MAIT cells. Bile was collected at the time of liver transplantation from patients with PSC (n = 28). The bile samples were either directly incubated with peripheral blood mononuclear cells from healthy donors or with antigen-presenting cells followed by co-culture with peripheral blood mononuclear cells. MAIT cell activation was assessed by flow cytometry. An anti-MR1 antibody was used to determine whether the activation was major histocompatibility complex class I–related protein (MR1) restricted. Biliary microbiota profiles were generated using 16S rRNA amplicon sequencing, and the abundance of the bacterial gene ribD was predicted. Eight of 28 bile samples could activate MAIT cells. This activation was partly MR1-dependent in five of eight bile samples. Microbial DNA was detected in 15 of 28 bile samples, including the five bile samples leading to MR1-dependent activation. A higher abundance of the ribD gene expression in the group of bile samples that could activate MAIT cells was predicted on the basis of the 16S sequencing. In co-culture experiments, cholangiocytes could take up and present biliary antigens to MAIT cells. These findings suggest a pathophysiological pathway in PSC connecting the immune system and the microbiome.

• Yu, Jingru; Refsum, Erle; Helsingen, Lise Mørkved; Folseraas, Trine; Ploner, Alexander & Wieszczy, Paulina [Show all 15 contributors for this article] (2022). Risk of hepato-pancreato-biliary cancer is increased by primary sclerosing cholangitis in patients with inflammatory bowel disease: A population-based cohort study. United European Gastroenterology Journal (UEG Journal). ISSN 2050-6406. 10(2), p. 212–224. doi: 10.1002/ueg2.12204. Full text in Research Archive
• Tønnessen, Theis Christian; Melleby, Arne Olav; Hauge-Iversen, Ida Marie; Espe, Emil Knut Stenersen; Ahmed, Muhammad Shakil & Ueland, Thor [Show all 12 contributors for this article] (2022). Impact of delayed type hypersensitivity arthritis on development of heart failure by aortic constriction in mice. PLOS ONE. ISSN 1932-6203. 17(1). doi: 10.1371/journal.pone.0262821. Full text in Research Archive Show summary

  Aims Patients with rheumatoid arthritis (RA) have increased risk of heart failure (HF). The mechanisms and cardiac prerequisites explaining this association remain unresolved. In this study, we sought to determine the potential cardiac impact of an experimental model of RA in mice subjected to HF by constriction of the ascending aorta. Methods Aorta was constricted via thoracotomy and placement of o-rings with inner diameter 0.55 mm or 0.66 mm, or sham operated. RA-like phenotype was instigated by delayed-type hypersensitivity arthritis (DTHA) two weeks after surgery and re-iterated after additional 18 days. Cardiac magnetic resonance imaging (MRI) was performed before surgery and at successive time points throughout the study. Six weeks after surgery the mice were euthanized, blood and tissue were collected, organ weights were documented, and expression levels of cardiac foetal genes were analysed. In a supplemental study, DTHA-mice were euthanized throughout 14 days after induction of arthritis, and blood was analysed for important markers and mediators of RA (SAP, TNF-α and IL-6). In order to put the latter findings into clinical context, the same molecules were analysed in serum from untreated RA patients and compared to healthy controls. Results Significant elevations of inflammatory markers were found in both patient- and murine blood. Furthermore, the DTHA model appeared clinically relevant when compared to the inflammatory responses observed in three prespecified RA severity disease states. Two distinct trajectories of cardiac dysfunction and HF development were found using the two o-ring sizes. These differences were consistent by both MRI, organ weights and cardiac foetal gene expression levels. Still, no difference within the HF groups, nor within the sham groups, could be found when DTHA was induced. Conclusion DTHA mediated systemic inflammation did not cause, nor modify HF caused by aortic constriction. This indicates other prerequisites for RA-induced cardiac dysfunction.

• Sampaziotis, Fotios; Muraro, Daniele; Tysoe, Olivia C.; Sawiak, Stephen; Beach, Timothy E. & Godfrey, Edmund M. [Show all 40 contributors for this article] (2021). Cholangiocyte organoids can repair bile ducts after transplantation in the human liver. Science. ISSN 0036-8075. 371(6531), p. 839–846. doi: 10.1126/science.aaz6964.
• Zimmer, Christine L.; Filipovic, Iva; Cornillet, Martin; O’Rourke, Colm J.; Berglin, Lena & Jansson, Hannes [Show all 20 contributors for this article] (2021). Mucosal-associated invariant T-cell tumor infiltration predicts long-term survival in cholangiocarcinoma. Hepatology. ISSN 0270-9139. doi: 10.1002/hep.32222. Full text in Research Archive
• Jiang, Xiaojun; Bergquist, Annika; Löscher, Britt-Sabina; Venkatesh, Geetha; Mold, Jeff E. & Holm, Kristian [Show all 15 contributors for this article] (2021). A heterozygous germline CD100 mutation in a family with primary sclerosing cholangitis. Science Translational Medicine. ISSN 1946-6234. 13(582). doi: 10.1126/scitranslmed.abb0036.
• Hausken, John; Haugaa, Håkon; Hagness, Morten; Line, Pål-Dag; Melum, Espen & Tønnessen, Tor Inge (2021). Thoracic Epidural Analgesia for Postoperative Pain Management in Liver Transplantation: A 10-year Study on 685 Liver Transplant Recipients. Transplantation direct. ISSN 2373-8731. 7(2), p. 1–6. doi: 10.1097/TXD.0000000000001101. Full text in Research Archive Show summary

  Background. Thoracic epidural analgesia (TEA) is not widely used for postoperative pain management in liver transplantation due to hepatic coagulopathy-related increased risk of inducing an epidural hematoma. However, an increasing number of patients are transplanted for other indications than the end-stage liver disease and without coagulopathy allowing insertion of an epidural catheter. Methods. This study is a retrospective observational single-center study of all adult patients undergoing first-time liver transplantation at Oslo University Hospital between January 1, 2008, and December 31, 2017. Data regarding patient characteristics were obtained from the Nordic liver transplant registry, medical records, and pain registration forms. Patients without coagulopathy (international normalized ratio <1.5 and platelets >100 × 109/L) were eligible for TEA. Results. Out of 685 first-time liver transplantations in a 10-year period, 327 received TEA, and 358 did not. The median Model of End-stage Liver Disease score was lower in the TEA group than in the non-TEA-group (9 versus 17, P < 0.001), and fewer patients were hospitalized preoperatively (16 versus 127, P < 0.001). The median international normalized ratio (1.1 versus 1.6, P < 0.001) and platelet count (190 versus 78, P < 0.001) were different between the TEA and non-TEA groups. There were no serious complications related to insertion or removal of the TEA catheters. Patients in the TEA group had less pain with a mean numeric rating scale at postoperative days 0–5 of 1.4 versus 1.8 (P = 0.008). Nearly 50% of the patients were prescribed opioids when discharged from hospital (non-TEA 154 versus TEA 158, P = 0.23), and there was no difference after 1 year (P = 0.718). Conclusions. Our report revealed very good pain control with both TEA and the non-TEA modality. TEA was without any serious complications like epidural hematoma or infection/abscess in selected liver transplant recipients without severe coagulopathy. Opioid prescription at hospital discharge and by 1-year follow-up did not differ between the groups.

• Harrison, Sean; Siller, Richard; Tanaka, Yoshiaki; Xiang, Yangfei; Patterson, Benjamin & Kempf, Henning [Show all 29 contributors for this article] (2020). Scalable production of tissue-like vascularised liver organoids from human PSCs. bioRxiv. ISSN 2692-8205. doi: 10.1101/2020.12.02.406835.
• Lissing, Mattias; Nowak, Greg; Adam, René; Karam, Vincent; Boyd, Alexander & Gouya, Laurent [Show all 21 contributors for this article] (2020). Liver Transplantation for Acute Intermittent Porphyria. Liver transplantation. ISSN 1527-6465. doi: 10.1002/lt.25959. Full text in Research Archive
• Louwe, Maria Cornelia; Olsen, Maria Belland; Kaasbøll, Ole Jørgen; Yang, Kuan; Fosshaug, Linn Elisabeth Lillerud & Alfsnes, Katrine [Show all 25 contributors for this article] (2020). Absence of NLRP3 Inflammasome in Hematopoietic Cells Reduces Adverse Remodeling After Experimental Myocardial Infarction. JACC: Basic to Translational Science. ISSN 2452-302X. 5(12), p. 1210–1224. doi: 10.1016/j.jacbts.2020.09.013. Full text in Research Archive
• Valestrand, Laura Cecilie; Berntsen, Natalie Lie; Fei, Zheng; Schrumpf, Erik; Hansen, Simen Hyll & Karlsen, Tom Hemming [Show all 10 contributors for this article] (2020). Lipid antigens in bile from patients with chronic liver diseases activate natural killer T cells. Clinical and Experimental Immunology. ISSN 0009-9104. doi: 10.1111/cei.13541. Full text in Research Archive
• Melum, Espen; Jiang, Xiaojun; Baker, Kirsti B; Macedo, M Fatima; Fritsch, Jürgen & Dowds, C Marie [Show all 21 contributors for this article] (2019). Control of CD1d-restricted antigen presentation and inflammation by sphingomyelin. Nature Immunology. ISSN 1529-2908. 20(12), p. 1644–1655. doi: 10.1038/s41590-019-0504-0. Full text in Research Archive
• Tysoe, Olivia C.; Justin, Alexander W.; Brevini, Teresa; Chen, Si Emma; Mahbubani, Krishnaa T. & Frank, Anna Katharina [Show all 12 contributors for this article] (2019). Isolation and propagation of primary human cholangiocyte organoids for the generation of bioengineered biliary tissue. Nature Protocols. ISSN 1754-2189. 14, p. 1884–1925. doi: 10.1038/s41596-019-0168-0.
• Maroni, L.; Pinto, C; Giordano, Debora M; Saccomanno, Stefania; Banales, Jesus M. & Spallacci, D [Show all 18 contributors for this article] (2018). Ageing-related expression of Twinfilin-1 regulates cholangiocyte biological response to injury. Hepatology. ISSN 0270-9139. doi: 10.1002/hep.30466.
• Pihlstrøm, Hege; Mjøen, Geir; Mucha, S; Franke, Andre; Jardine, A & Fellstrom, B [Show all 9 contributors for this article] (2018). Genetic markers associated with long-term cardiovascular outcome in kidney transplant recipients. American Journal of Transplantation. ISSN 1600-6135. doi: 10.1111/ajt.15191.
• Holmer, Magnus; Melum, Espen; Isoniemi, Helena; Ericzon, Bo-Göran; Castedal, Maria & Nordin, Arno [Show all 12 contributors for this article] (2018). Nonalcoholic fatty liver disease is an increasing indication for liver transplantation in the Nordic countries. Liver international (Print). ISSN 1478-3223. 38(11), p. 2082–2090. doi: 10.1111/liv.13751.
• Thorgersen, Ebbe Billmann; Melum, Espen; Folseraas, Trine; Larsen, Stein Gunnar & Line, Pål Dag (2018). Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei in a liver-transplanted patient: A case report. World Journal of Surgical Oncology (WJSO). ISSN 1477-7819. 16:180, p. 1–5. doi: 10.1186/s12957-018-1482-7. Full text in Research Archive
• Berntsen, Natalie Lie; Fosby, Bjarte; Tan, Corey; Reims, Henrik Mikael; Øgaard, Jonas & Jiang, Xiaojun [Show all 12 contributors for this article] (2018). Natural killer T cells mediate inflammation in the bile ducts. Mucosal Immunology. ISSN 1933-0219. p. 1–9. doi: 10.1038/s41385-018-0066-8.
• Sampaziotis, Fotios; Justin, Alexander W.; Tysoe, Olivia C.; Sawiak, Stephen; Godfrey, Edmund M. & Upponi, Sara S. [Show all 43 contributors for this article] (2017). Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nature Medicine. ISSN 1078-8956. 23(8), p. 954–963. doi: 10.1038/nm.4360.
• Chellappa, Stalin ; Hugenschmidt, Harald; Hagness, Morten; Subramani, Saranya; Melum, Espen & Line, Pål Dag [Show all 10 contributors for this article] (2017). CD8+ T Cells That Coexpress RORγt and T-bet Are Functionally Impaired and Expand in Patients with Distal Bile Duct Cancer. Journal of Immunology. ISSN 0022-1767. 198(4), p. 1729–1739. doi: 10.4049/jimmunol.1600061.
• Alberts, R; de Vries, EMG; Goode, EC; Jiang, Xiaojun; Sampaziotis, Fotios & Rombouts, K [Show all 50 contributors for this article] (2017). Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis. Gut. ISSN 0017-5749. 67(8), p. 1517–1524. doi: 10.1136/gutjnl-2016-313598.
• Berntsen, Natalie Lie; Fosby, Bjarte; Valestrand, Laura Cecilie; Tan, Corey; Reims, Henrik Mikael & Schrumpf, Elisabeth [Show all 9 contributors for this article] (2017). Establishment of a surgical bile duct injection technique giving direct access to the bile ducts for studies of the murine biliary tree. American Journal of Physiology - Gastrointestinal and Liver Physiology. ISSN 0193-1857. 314(3), p. G349–G359. doi: 10.1152/ajpgi.00124.2017.
• Henriksen, Eva Kristine Klemsdal; Viken, Marte K; Wittig, Michael; Holm, Kristian; Folseraas, Trine & Mucha, Sören [Show all 29 contributors for this article] (2017). HLA haplotypes in primary sclerosing cholangitis patients of admixed and non-European ancestry. HLA. ISSN 2059-2302. 90(4), p. 228–233. doi: 10.1111/tan.13076.
• Jiang, Xiaojun; Björkström, Niklas K. & Melum, Espen (2017). Intact CD100-CD72 interaction necessary for TCR-induced T cell proliferation. Frontiers in Immunology. ISSN 1664-3224. 8:765. doi: 10.3389/fimmu.2017.00765.
• Landskron, Johannes; Kraggerud, Sigrid M.; Wik, Elisabeth; Dørum, Anne; Bjørnslett, Merete Pauline & Melum, Espen [Show all 11 contributors for this article] (2017). C77G in PTPRC (CD45) is no risk allele for ovarian cancer, but associated with less aggressive disease. PLOS ONE. ISSN 1932-6203. 12:e0182030(7), p. 1–12. doi: 10.1371/journal.pone.0182030. Full text in Research Archive
• Vesterhus, Mette; Holm, Anders; Hov, Johannes Espolin Roksund; Nygård, Ståle; Schrumpf, Erik & Melum, Espen [Show all 23 contributors for this article] (2017). Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis. Journal of Hepatology. ISSN 0168-8278. 66(6), p. 1214–1222. doi: 10.1016/j.jhep.2017.01.019.
• Meijerink, Hinta; White, Richard; Løvlie, Astrid Louise; De Blasio, Birgitte Freiesleben; Dalgard, Olav & Amundsen, Ellen Johanna [Show all 8 contributors for this article] (2017). Modelling the burden of hepatitis C infection among people who inject drugs in Norway, 1973–2030. BMC Infectious Diseases. ISSN 1471-2334. 17. doi: 10.1186/s12879-017-2631-2. Full text in Research Archive
• Schrumpf, Elisabeth; Jiang, Xiaojun; Zeissig, Sebastian; Pollheimer, Marion J.; Anmarkrud, Jarl Andreas & Tan, Corey [Show all 10 contributors for this article] (2017). The role of natural killer T cells in a mouse model with spontaneous bile duct inflammation. Physiological Reports. ISSN 2051-817X. 5:e13117(4), p. 1–12. doi: 10.14814/phy2.13117.
• Schrumpf, Elisabeth; Kummen, Martin; Valestrand, Cecilie; Greiner, Thomas U; Holm, Kristian & Arulampalam, Velmurugesam [Show all 13 contributors for this article] (2017). The gut microbiota contributes to a mouse model of spontaneous bile duct inflammation. Journal of Hepatology. ISSN 0168-8278. 66(2), p. 382–389. doi: 10.1016/j.jhep.2016.09.020. Full text in Research Archive
• Maroni, Luca; Agostinelli, Laura; Saccomanno, Stefania; Pinto, Claudio; Giordano, Debora M & Rychilcki, Chiara [Show all 14 contributors for this article] (2017). Nlrp3 activation induces Il-18 synthesis and affects the epithelial barrier function in reactive cholangiocytes. American Journal of Pathology. ISSN 0002-9440. 187(2), p. 366–376. doi: 10.1016/j.ajpath.2016.10.010.
• Henriksen, Eva Kristine Klemsdal; Jørgensen, Kristin Kaasen; Kaveh, Fatemeh; Holm, Kristian; Hamm, David & Olweus, Johanna [Show all 14 contributors for this article] (2017). Gut and liver T-cells of common clonal origin in primary sclerosing cholangitis-inflammatory bowel disease. Journal of Hepatology. ISSN 0168-8278. 66(1), p. 116–122. doi: 10.1016/j.jhep.2016.09.002.
• Gunasekaran, Stalin Chellappa; Hugenschmidt, Harald; Hagness, Morten; Subramani, Saranya; Melum, Espen & Line, Pål Dag [Show all 10 contributors for this article] (2017). CD8+ T cells that coexpress ROR?t and T-bet are functionally impaired and expand in patients with distal bile duct cancer. Journal of Immunology. ISSN 0022-1767. 198(4), p. 1729–1739. doi: 10.4049/jimmunol.1600061.
• Vesterhus, Mette & Melum, Espen (2016). Prognostic biomarkers and surrogate end points in PSC. Liver international (Print). ISSN 1478-3223. 36(12), p. 1748–1751. doi: 10.1111/liv.13216.
• Ji, Sun-Gou; Juran, Brian D.; Mucha, Sören; Folseraas, Trine; Jostins, Luke & Melum, Espen [Show all 39 contributors for this article] (2016). Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease. Nature Genetics. ISSN 1061-4036. 49(20), p. 269–273. doi: 10.1038/ng.3745.
• Pihlstrøm, Hege; Mjøen, Geir; Mucha, S; Haraldsen, Guttorm; Franke, A & Jardine, A [Show all 9 contributors for this article] (2016). Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients: A Validation Study. American Journal of Transplantation. ISSN 1600-6135. 17(2), p. 528–533. doi: 10.1111/ajt.13995.
• Liaskou, Evaggelia; Henriksen, Eva Kristine Klemsdal; Holm, Kristian; Kaveh, Fatemeh; Hamm, D & Fear, Janine [Show all 13 contributors for this article] (2016). High-throughput T-cell receptor sequencing across chronic liver diseases reveals distinct disease-associated repertoires. Hepatology. ISSN 0270-9139. 63(5), p. 1608–1619. doi: 10.1002/hep.28116. Show summary

  Hepatic T-cell infiltrates and a strong genetic human leukocyte antigen association represent characteristic features of various immune-mediated liver diseases. Conceptually the presence of disease-associated antigens is predicted to be reflected in T-cell receptor (TCR) repertoires. Here, we aimed to determine if disease-associated TCRs could be identified in the nonviral chronic liver diseases primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and alcoholic liver disease (ALD). We performed high-throughput sequencing of the TCRβ chain complementarity-determining region 3 of liver-infiltrating T cells from PSC (n = 20), PBC (n = 10), and ALD (n = 10) patients, alongside genomic human leukocyte antigen typing. The frequency of TCRβ nucleotide sequences was significantly higher in PSC samples (2.53 ± 0.80, mean ± standard error of the mean) compared to PBC samples (1.13 ± 0.17, P < 0.0001) and ALD samples (0.62 ± 0.10, P < 0.0001). An average clonotype overlap of 0.85% was detected among PSC samples, significantly higher compared to the average overlap of 0.77% seen within the PBC (P = 0.024) and ALD groups (0.40%, P < 0.0001). From eight to 42 clonotypes were uniquely detected in each of the three disease groups (≥30% of the respective patient samples). Multiple, unique sequences using different variable family genes encoded the same amino acid clonotypes, providing additional support for antigen-driven selection. In PSC and PBC, disease-associated clonotypes were detected among patients with human leukocyte antigen susceptibility alleles. Conclusion: We demonstrate liver-infiltrating disease–associated clonotypes in all three diseases evaluated, and evidence for antigen-driven clonal expansions. Our findings indicate that differential TCR signatures, as determined by high-throughput sequencing, may represent an imprint of distinctive antigenic repertoires present in the different chronic liver diseases; this thereby opens up the prospect of studying disease-relevant T cells in order to better understand and treat liver disease. (Hepatology 2015)

• Andersen, Ina Marie; Fosby, Bjarte; Boberg, Kirsten Muri; Clausen, Ole Petter Fraas; Jebsen, Peter Wilhelm & Melum, Espen [Show all 10 contributors for this article] (2015). Indications and Outcomes in Liver Transplantation in Patients with Primary Sclerosing Cholangitis in Norway. Transplantation direct. ISSN 2373-8731. 1(9). doi: 10.1097/TXD.0000000000000548.
• Zeissig, Sebastian; Petersen, Britt-Sabina; Tomczak, Michal; Melum, Espen; Huc-Claustre, Emilie & Dougan, Stephanie K. [Show all 14 contributors for this article] (2015). Early-onset Crohn's disease and autoimmunity associated with a variant in CTLA-4. Gut. ISSN 0017-5749. 64(12), p. 1889–1897. doi: 10.1136/gutjnl-2014-308541.
• Schrumpf, Elisabeth; Tan, Corey; Karlsen, Tom Hemming; Sponheim, Jon; Björkström, Niklas K. & Sundnes, Olav [Show all 16 contributors for this article] (2015). The biliary epithelium presents antigens to and activates natural killer T cells. Hepatology. ISSN 0270-9139. 62(4), p. 1249–1259. doi: 10.1002/hep.27840.
• Sampaziotis, Fotios; De Brito, Miguel Cardoso; Madrigal, Pedro; Bertero, Alessandro; Saeb-Parsy, Kourosh & Soares, Filipa A.C. [Show all 17 contributors for this article] (2015). Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nature Biotechnology. ISSN 1087-0156. 33(8), p. 845–852. doi: 10.1038/nbt.3275.
• Olin, Per Bertil Mårten; Hausken, John; Foss, Aksel; Karlsen, Tom Hemming; Melum, Espen & Haugaa, Håkon (2015). Continuous molecular adsorbent recirculating system treatment in 69 patients listed for liver transplantation. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 50(9), p. 1127–1134. doi: 10.3109/00365521.2015.1027262.
• Fosby, Bjarte; Melum, Espen; Bjøro, Kristian; Bennet, William; Rasmussen, Allan & Andersen, Ina Riise [Show all 30 contributors for this article] (2015). Liver transplantation in the Nordic countries-An intention to treat and post-transplant analysis from the Nordic Liver Transplant Registry 1982-2013. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 50(6), p. 797–808. doi: 10.3109/00365521.2015.1036359.
• Huang, Yu-Hwa; Zhu, Chen; Kondo, Yasuyuki; Anderson, Ana C.; Gandhi, Amit & Russell, Andrew [Show all 24 contributors for this article] (2015). CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature. ISSN 0028-0836. 517, p. 386–390. doi: 10.1038/nature13848.
• Næss, Sigrid; Lie, Benedicte Alexandra; Melum, Espen; Olsson, Marita; Hov, Johannes Espolin Roksund & Croucher, PJP [Show all 15 contributors for this article] (2014). Refinement of the MHC risk map in a Scandinavian primary sclerosing cholangitis population. PLOS ONE. ISSN 1932-6203. 9:e0114486(12). doi: 10.1371/journal.pone.0114486.
• Eskesen, Arne N; Bjøro, Kristian; Aandahl, Einar Martin; Line, Pål Dag & Melum, Espen (2014). Low use of surveillance and early diagnosis of hepatocellular carcinoma in Norway-A population-based cohort study. Cancer Epidemiology. ISSN 1877-7821. 38(6), p. 741–747. doi: 10.1016/j.canep.2014.10.005.
• Fosby, Bjarte; Næss, Sigrid; Hov, Johannes Espolin Roksund; Traherne, James; Boberg, Kirsten Muri & Trowsdale, John [Show all 12 contributors for this article] (2014). HLA variants related to primary sclerosing cholangitis influence rejection after liver transplantation. World Journal of Gastroenterology (WJG). ISSN 1007-9327. 20(14), p. 3986–4000. doi: 10.3748/wjg.v20.i14.3986.
• Henriksen, Eva Kristine Klemsdal; Melum, Espen & Karlsen, Tom Hemming (2014). Update on primary sclerosing cholangitis genetics. Current Opinion in Gastroenterology. ISSN 0267-1379. 30(3), p. 310–319. doi: 10.1097/MOG.0000000000000052.
• Fickert, Peter; Pollheimer, Marion J.; Beuers, Ulrich; Lackner, Carolin; Hirschfield, Gideon & Housset, Chantal [Show all 16 contributors for this article] (2014). Characterization of animal models for primary sclerosing cholangitis (PSC). Journal of Hepatology. ISSN 0168-8278. 60(6), p. 1290–1303. doi: 10.1016/j.jhep.2014.02.006.
• Næss, Sigrid; Björnsson, Einar; Anmarkrud, Jarl Andreas; Al Mamari, Said; Juran, Brian D. & Lazaridis, Konstantinos N. [Show all 15 contributors for this article] (2014). Small duct primary sclerosing cholangitis without inflammatory bowel disease is genetically different from large duct disease. Liver international (Print). ISSN 1478-3223. 34(10), p. 1488–1495. doi: 10.1111/liv.12492.
• Liu, Jimmy Z.; Hov, Johannes Espolin Roksund; Folseraas, Trine; Ellinghaus, E; Rushbrook, SM & Doncheva, NT [Show all 84 contributors for this article] (2013). Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis. Nature Genetics. ISSN 1061-4036. 45(6), p. 670–675. doi: 10.1038/ng.2616.
• Forster, Michael; Forster, Peter; Elsharawy, Abdou; Hemmrich, Georg; Kreck, Benjamin & Wittig, Michael [Show all 18 contributors for this article] (2013). From next-generation sequencing alignments to accurate comparison and validation of single-nucleotide variants: the pibase software. Nucleic Acids Research (NAR). ISSN 0305-1048. 41(1). doi: 10.1093/nar/gks836.
• Ellinghaus, David; Folseraas, Trine; Holm, Kristian; Ellinghaus, Eva; Melum, Espen & Balschun, Tobias [Show all 37 contributors for this article] (2013). Genome-wide association analysis in Primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4. Hepatology. ISSN 0270-9139. 58(3), p. 1074–1083. doi: 10.1002/hep.25977.
• Eskesen, Arne N; Melum, Espen; Moghaddam, Amir; Bjøro, Kristian; Verbaan, Hans & Ring-Larsen, Helmer [Show all 7 contributors for this article] (2012). Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic anemia and dose reduction in an HCV G2/G3 cohort. European Journal of Gastroenterology and Hepathology. ISSN 0954-691X. 24(8), p. 890–896. doi: 10.1097/MEG.0b013e3283546efd.
• Srivastava, Brijesh; Mells, George F.; Cordell, Heather J.; Muriithi, Agnes; Brown, Matthew & Ellinghaus, Eva [Show all 13 contributors for this article] (2012). Fine mapping and replication of genetic risk loci in primary sclerosing cholangitis. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 47(7), p. 820–826. doi: 10.3109/00365521.2012.682090.
• Folseraas, Trine; Melum, Espen; Rausch, Philipp; Juran, Brian D.; Ellinghaus, Eva & Shiryaev, Alexey [Show all 40 contributors for this article] (2012). Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. Journal of Hepatology. ISSN 0168-8278. 57(2), p. 366–375. doi: 10.1016/j.jhep.2012.03.031.
• Folseraas, Trine; Melum, Espen; Franke, Andre & Karlsen, Tom Hemming (2011). Genetics in primary sclerosing cholangitis. Baillière's Best Practice & Research : Clinical Gastroenterology. ISSN 1521-6918. 25(6), p. 713–726. doi: 10.1016/j.bpg.2011.09.010. Show summary

  Primary sclerosing cholangitis (PSC) is a chronic and severe inflammatory disease leading to fibrotic bile duct destruction and in most cases liver cirrhosis. As in other complex genetic diseases, the sibling risk of PSC is more than ten times that of the general population. Recent genome-wide association studies have consistently identified several genetic susceptibility loci. The overlap of these loci with susceptibility loci in other chronic inflammatory diseases is considerable, and offers intriguing opportunities for transfer of pathogenetic knowledge and potentially treatment options. In the present article we summarise the present knowledge on PSC genetics with a particular emphasis on the major histocompatibility complex (MHC). We discuss the clinical relevance of the risk loci and elaborate on the insight that may be obtained from associated inflammatory conditions and existing murine knock-out models. (C) 2011 Elsevier Ltd. All rights reserved.

• Folseraas, Trine; Melum, Espen; Franke, Andre & Karlsen, Tom Hemming (2011). Best Practice & Research Clinical Gastroenterology. Baillière's Best Practice & Research : Clinical Gastroenterology. ISSN 1521-6918. 25(6), p. 713–726. doi: 10.1016/j.bpg.2011.09.010. Show summary

  Primary sclerosing cholangitis (PSC) is a chronic and severe inflammatory disease leading to fibrotic bile duct destruction and in most cases liver cirrhosis. As in other complex genetic diseases, the sibling risk of PSC is more than ten times that of the general population. Recent genome-wide association studies have consistently identified several genetic susceptibility loci. The overlap of these loci with susceptibility loci in other chronic inflammatory diseases is considerable, and offers intriguing opportunities for transfer of pathogenetic knowledge and potentially treatment options. In the present article we summarise the present knowledge on PSC genetics with a particular emphasis on the major histocompatibility complex (MHC). We discuss the clinical relevance of the risk loci and elaborate on the insight that may be obtained from associated inflammatory conditions and existing murine knock-out models. (C) 2011 Elsevier Ltd. All rights reserved.

• Melum, Espen; Franke, Andre; Schramm, Christoph; Weismüller, Tobias J.; Gotthardt, Daniel & Offner, Felix A. [Show all 43 contributors for this article] (2011). Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci. Nature Genetics. ISSN 1061-4036. 43(1), p. 17–19. doi: 10.1038/ng.728.
• Moghaddam, Amir; Melum, Espen; Reinton, Nils; Ring-Larsen, Helmer; Verbaan, Hans & Bjøro, Kristian [Show all 7 contributors for this article] (2011). IL28B Genetic Variation and Treatment Response in Patients with Hepatitis C Virus Genotype 3 Infection. Hepatology. ISSN 0270-9139. 53(3), p. 746–754. doi: 10.1002/hep.24154.
• Melum, Espen; May, Sandra; Schilhabel, Markus B.; Thomsen, Ingo; Karlsen, Tom Hemming & Rosenstiel, Philip [Show all 8 contributors for this article] (2010). SNP Discovery Performance of Two Second-Generation Sequencing Platforms in the NOD2 Gene Region. Human Mutation. ISSN 1059-7794. 31(7), p. 875–885. doi: 10.1002/humu.21276.
• Holm, Kristian; Melum, Espen; Franke, Andre & Karlsen, Tom Hemming (2010). SNPexp - A web tool for calculating and visualizing correlation between HapMap genotypes and gene expression levels. BMC Bioinformatics. ISSN 1471-2105. 11. doi: 10.1186/1471-2105-11-600.
• Karlsen, Tom Hemming; Melum, Espen & Franke, Andre (2010). The Utility of Genome-Wide Association Studies in Hepatology. Hepatology. ISSN 0270-9139. 51(5), p. 1833–1842. doi: 10.1002/hep.23564.
• Lorentzen, Åslaug Rudjord; Melum, Espen; Ellinghaus, Eva; Smestad, Cathrine; Mero, Inger-Lise & Aarseth, Jan Harald [Show all 12 contributors for this article] (2010). Association to the Glypican-5 gene in multiple sclerosis. Journal of Neuroimmunology. ISSN 0165-5728. 226(1-2), p. 194–197. doi: 10.1016/j.jneuroim.2010.07.003.
• Evang, Johan Arild; Borota, Olivera Casar; Melum, Espen; Holm, Ruth; Ramm-Pettersen, Jon-Terje & Bollerslev, Jens [Show all 7 contributors for this article] (2010). HDAC2 expression and variable number of repeats in exon 1 of the HDAC2 gene in corticotroph adenomas. Clinical Endocrinology. ISSN 0300-0664. 73(2), p. 229–235. doi: 10.1111/j.1365-2265.2010.03805.x.
• Hov, Johannes Espolin Roksund; Keitel, V; Lærdahl, Jon Kristen; Spomer, L; Ellinghaus, E & ElSharawy, A [Show all 36 contributors for this article] (2010). Mutational Characterization of the Bile Acid Receptor TGR5 in Primary Sclerosing Cholangitis. PLOS ONE. ISSN 1932-6203. 5(8). doi: 10.1371/journal.pone.0012403.
• Karlsen, Tom Hemming; Franke, Andre; Melum, Espen; Kaser, Arthur; Hov, Johannes Espolin Roksund & Balschun, Tobias [Show all 32 contributors for this article] (2010). Genome-Wide Association Analysis in Primary Sclerosing Cholangitis. Gastroenterology. ISSN 0016-5085. 138(3), p. 1102–1111. doi: 10.1053/j.gastro.2009.11.046.
• Melum, Espen; Karlsen, TH; Schrumpf, Erik; Bergquist, A; Thorsby, Erik & Boberg, Kirsten Muri [Show all 7 contributors for this article] (2008). Cholanglocarcinoma in primary sclerosing cholangitis is associated with NKG2D Polymorphisms. Hepatology. ISSN 0270-9139. 47, p. 90–96. doi: 10.1002/hep.21964.

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• Huang, Yu-Hwa; Zhu, Chen; Kondo, Yasuyuki; Anderson, Ana C.; Gandhi, Amit & Russell, Andrew [Show all 24 contributors for this article] (2024). Correction to: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion (Nature, (2015), 517, 7534, (386-390), 10.1038/nature13848). Nature. ISSN 0028-0836. doi: 10.1038/s41586-024-07164-y.
• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Show all 40 contributors for this article] (2023). Author Correction: Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants (npj Vaccines, (2022), 7, 1, (174), 10.1038/s41541-022-00586-7). npj Vaccines. ISSN 2059-0105. 8(1). doi: 10.1038/s41541-023-00600-6.
• Jiang, Xiaojun & Melum, Espen (2021). The Role of Natural Killer Cells in Nonalcoholic Steatohepatitis: An Ongoing Debate. Cellular and Molecular Gastroenterology and Hepatology (CMGH). ISSN 2352-345X. doi: 10.1016/j.jcmgh.2021.10.006.
• Paquin-Proulx, Dominic; Greenspun, Benjamin C.; Pasquet, Lise; Strunz, Benedikt; Aleman, Soo & Falconer, Karolin [Show all 12 contributors for this article] (2018). IL13R?2 expression identifies tissue-resident IL-22-producing PLZF+ innate T cells in the human liver. European Journal of Immunology. ISSN 0014-2980. 48(8), p. 1329–1335. doi: 10.1002/eji.201747334.
• Srivastava, B; Mells, G.; Cordell, H.; Murithii, A.; Brown, M. & Ellinghaus, E [Show all 13 contributors for this article] (2012). FINE MAPPING OF THE IL-2/IL-21 AND IL2RA LOCI IN PRIMARY SCLEROSING CHOLANGITIS. Journal of Hepatology. ISSN 0168-8278. 56, p. S15–S16.
• Srivastava, B; Mells, George F.; Cordell, H.J.; Muriithi, Agnes; Brown, M. & Ellinghaus, E [Show all 13 contributors for this article] (2012). FINE MAPPING OF THE IL-2/IL-21 AND IL2RA LOCI IN PRIMARY SCLEROSING CHOLANGITIS. Gut. ISSN 0017-5749. 61, p. A212–A213. doi: 10.1136/gutjnl-2012-302514c.70.
• Fosby, Bjarte; Karlsen, Tom Hemming & Melum, Espen (2012). Recurrence and rejection in liver transplantation for primary sclerosing cholangitis. World Journal of Gastroenterology (WJG). ISSN 1007-9327. 18(1), p. 1–15. doi: 10.3748/wjg.v18.i1.1.
• Eskesen, Arne N; Melum, Espen; Moghaddam, Amir; Bjøro, K; Verbaan, H & Ring-Larsen, H. [Show all 7 contributors for this article] (2011). GENETIC VARIANTS AT THE ITPA LOCUS PROTECTS AGAINST RIBAVIRIN-INDUCED HEMOLYTIC ANEMIA - A REPLICATION STUDY IN A SCANDINAVIAN HCV G2/G3 COHORT. Journal of Hepatology. ISSN 0168-8278. 54, p. S455–S455.
• Lorentzen, Åslaug Rudjord; Melum, Espen; Buchert, Eva; SMESTAD, CATHRINE; Mero, Inger-Lise & Aarseth, Jan Harald [Show all 12 contributors for this article] (2010). Trend of association to the Glypican 5 gene region to multiple sclerosis. European Journal of Neurology. ISSN 1351-5101. 17, p. 221–221.
• Dalgard, Olav; Moghaddam, Amir; Verbaan, Hans; Ring-Larsen, Helmer; Bjøro, Kristian & Melum, Espen (2010). IL28B GENETIC VARIATION AND TREATMENT RESPONSE IN PATIENTS WITH HCV GENOTYPE 3 INFECTION. Hepatology. ISSN 0270-9139. 52(4), p. 751A–751A.
• Melum, Espen; Karlsen, TH; Bergquist, A; Schrumpf, Erik & Boberg, Kirsten Muri (2008). An interleukin-6 (IL-6) receptor polymorphism affecting serum levels of IL-6 does not increase the risk of cholangiocarcinoma in primary sclerosing cholangitis. American Journal of Gastroenterology. ISSN 0002-9270. 103, p. 1045–1045.
• Melum, Espen; Buch, Stephan; Schafmayer, Clemens; Kalthoff, Holger; Tepel, Jürgen & Schreiber, Stefan [Show all 8 contributors for this article] (2008). Investigation of cholangiocarcinoma associated NKG2D polymorphisms in colorectal carcinoma. International Journal of Cancer. ISSN 0020-7136. 123(1), p. 241–242. doi: 10.1002/ijc.23517.
• Melum, Espen & Karlsen, Tom Hemming (2010). From single markers to genome-wide association – A study of Primary Sclerosing Cholangitis genetics. Unipub forlag. ISSN 978-82-8072-614-8.

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