Article
Endocrinology & Metabolism
Huanhuan Pang, Yisheng Jiang, Jie Li, Yushen Wang, Meng Nie, Nan Xiao, Shuo Wang, Zhihong Song, Fansen Ji, Yafei Chang, Yu Zheng, Ke Yao, LiAng Yao, Shao Li, Peng Li, Lei Song, Xun Lan, Zhiheng Xu, Zeping Hu
Summary: Zika virus infection can lead to microcephaly in newborns, with extensive metabolic reprogramming events observed in infected mouse brains. Alterations in NAD(+) metabolism were identified as potential therapeutic targets for alleviating Zika virus-induced microcephaly, which was validated in vivo through NAD(+) or nicotinamide riboside supplementation.
Review
Allergy
Jocelyn R. Farmer, Gulbu Uzel
Summary: There is a growing recognition of the clinical overlap between primary immune deficiency and autoimmunity; detailed profiling of family history is crucial in the diagnostic process. Genetic and functional diagnostic approaches are complementary methods for identifying inborn errors of immunity, and extended immune phenotyping of family members can provide insight into disease inheritance and modifiers.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Review
Immunology
Md Munnaf Hossen, Yanmei Ma, Zhihua Yin, Yuhao Xia, Jing Du, Jim Yi Huang, Jennifer Jin Huang, Linghua Zou, Zhizhong Ye, Zhong Huang
Summary: Autoimmune diseases are characterized by autoreactive lymphocytes, self-antigen immune responses, and inflammation. CTLA-4, expressed in activated T cells, acts as a crucial regulator in the inflammatory response. This review highlights the structure, expression, and signaling pathways of CTLA-4 in reducing effector T-cell activity, enhancing Treg cell immunomodulatory ability, and its correlation with different autoimmune diseases. Additionally, it summarizes the current progress of CTLA-4 as a therapeutic target for various autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Allergy
David Egg, Ina Caroline Rump, Noriko Mitsuiki, Jessica Rojas-Restrepo, Maria-Elena Maccari, Charlotte Schwab, Annemarie Gabrysch, Klaus Warnatz, Sigune Goldacker, Virginia Patino, Daniel Wolff, Satoshi Okada, Seiichi Hayakawa, Yoshiaki Shikama, Kenji Kanda, Kohsuke Imai, Manabu Sotomatsu, Makoto Kuwashima, Takahiro Kamiya, Tomohiro Morio, Kazuaki Matsumoto, Takeshi Mori, Yuri Yoshimoto, Ingunn Dybedal, Maria Kanariou, Zeynep Yesim Kucuk, Hugo Chapdelaine, Lenka Petruzelkova, Hanns-Martin Lorenz, Kathleen E. Sullivan, Jennifer Heimall, Michel Moutschen, Jiri Litzman, Mike Recher, Michael H. Albert, Fabian Hauck, Suranjith Seneviratne, Jana Pachlopnik Schmid, Antonios Kolios, Gary Unglik, Christian Klemann, Scott Snapper, Lisa Giulino-Roth, Michael Svaton, Craig D. Platt, Sophie Hambleton, Olaf Neth, Geraldine Gosse, Steffen Reinsch, Dirk Holzinger, Yae-Jean Kim, Shahrzad Bakhtiar, Faranaz Atschekzei, Reinhold Schmidt, Georgios Sogkas, Shanmuganathan Chandrakasan, William Rae, Beata Derfalvi, Hanne Vibeke Marquart, Ahmet Ozen, Ayca Kiykim, Elif Karakoc-Aydiner, Pavlina Kralickova, Godelieve de Bree, Dimitra Kiritsi, Markus G. Seidel, Robin Kobbe, Jennifer Dantzer, Laia Alsina, Thais Armangue, Vassilios Lougaris, Philipp Agyeman, Sofia Nystrom, David Buchbinder, Peter D. Arkwright, Bodo Grimbacher
Summary: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) can lead to life-threatening autoimmune and lymphoproliferative complications. Treatment options include systemic immunosuppressants, immunoglobulin replacement, and stem cell transplantation for potential cure.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Paul Bastard, Kuang-Chih Hsiao, Qian Zhang, Jeremy Choin, Emma Best, Jie Chen, Adrian Gervais, Lucy Bizien, Marie Materna, Christine Harmant, Maguelonne Roux, Nicola L. Hawley, Daniel E. Weeks, Stephen T. McGarvey, Karla Sandoval, Carmina Barberena-Jonas, Consuelo D. Quinto-Cortes, Erika Hagelberg, Alexander J. Mentzer, Kathryn Robson, Boubacar Coulibaly, Yoann Seeleuthner, Benedetta Bigio, Zhi Li, Gilles Uze, Sandra Pellegrini, Lazaro Lorenzo, Zineb Sbihi, Sylvain Latour, Marianne Besnard, Tiphaine Adam de Beaumais, Evelyne Jacqz Aigrain, Vivien Beziat, Ranjan Deka, Litara Esera Tulifau, Satupa'itea Viali, Muagututi'a Sefuiva Reupena, Take Naseri, Peter McNaughton, Vanessa Sarkozy, Jane Peake, Annaliesse Blincoe, Sarah Primhak, Simon Stables, Kate Gibson, See-Tarn Woon, Kylie Marie Drake, Adrian V. S. Hill, Cheng-Yee Chan, Richard King, Rohan Ameratunga, Iotefa Teiti, Maite Aubry, Van-Mai Cao-Lormeau, Stuart G. Tangye, Shen-Ying Zhang, Emmanuelle Jouanguy, Paul Gray, Laurent Abel, Andres Moreno-Estrada, Ryan L. Minster, Lluis Quintana-Murci, Andrew C. Wood, Jean-Laurent Casanova
Summary: Autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity that leads to susceptibility to viral diseases. This study reports the presence of this deficiency in seven children of western Polynesian ancestry, highlighting its higher prevalence in this population.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Hui Wang, Gangduo Wang, Nivedita Banerjee, Yuejin Liang, Xiaotang Du, Paul J. Boor, Kristi L. Hoffman, M. Firoze Khan
Summary: The study found that dysbiosis of gut microbiome is associated with increased colonic oxidative stress, barrier dysfunction, inflammatory responses, and systemic autoimmune markers. Antioxidant treatment influenced the microbial composition and attenuated systemic autoimmunity in the MRL/lpr mice.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Limin Liu, Longyuan Hu, Haojun Long, Meiling Zheng, Zhi Hu, Ye He, Xiaofei Gao, Pei Du, Hongjun Zhao, Di Yu, Qianjin Lu, Ming Zhao
Summary: The study identified IL21-AS1 as a regulator of Tfh cell differentiation and autoimmune response. Through epigenetic mechanisms, IL21-AS1 activates IL21 transcription to promote germinal center response, shedding light on the molecular regulation of autoimmune pathogenesis and providing a potential new target for treating SLE.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Yongdan Wang, Pan Li, Shuai Mao, Zhuomao Mo, Zhirui Cao, Jin Luo, Meiling Zhou, Xifeng Liu, Shijun Zhang, Ling Yu
Summary: In the internal environment of spleen deficiency, exosomal CTLA-4 regulates the PTEN/CD44 signal pathway to promote the proliferation, self-renewal, and metastasis of liver cancer.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Kim M. van Pul, Jessica C. L. Notohardjo, Marieke F. Fransen, Bas D. Koster, Anita G. M. Stam, Dafni Chondronasiou, Sinead M. Lougheed, Joyce Bakker, Vinitha Kandiah, M. Petrousjka van den Tol, Karin Jooss, Ronald J. C. L. M. Vuylsteke, Alfons J. M. van den Eertwegh, Tanja D. de Gruijl
Summary: Locoregional CTLA-4 blockade is as effective as systemic delivery in inducing tumor eradication without immune-related side effects. Local administration of anti-CTLA-4 may offer a safe and promising adjuvant treatment strategy for patients with early-stage melanoma.
SCIENCE IMMUNOLOGY
(2022)
Article
Immunology
Kim M. van Pul, Jessica C. L. Notohardjo, Marieke F. Fransen, Bas D. Koster, Anita G. M. Stam, Dafni Chondronasiou, Sinead M. Lougheed, Joyce Bakker, Vinitha Kandiah, M. Petrousjka van den Tol, Karin Jooss, Ronald J. C. L. M. Vuylsteke, Alfons J. M. van den Eertwegh, Tanja D. de Gruijl
Summary: Local blockade of CTLA-4 can effectively induce tumor eradication and demonstrate good safety and tolerability in early-stage melanoma patients, with positive effects on migratory dendritic cells and effector T cells activation.
SCIENCE IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Gil-Ran Kim, Won-Ju Kim, Sangho Lim, Hong-Gyun Lee, Ja-Hyun Koo, Kyung-Ho Nam, Sung-Min Kim, Sung-Dong Park, Je-Min Choi
Summary: The study demonstrates that a novel chimeric CTLA-4 signaling peptide can induce regulatory T cells effectively in vivo, showing potential therapeutic effects for autoimmune diseases such as multiple sclerosis.
Review
Pediatrics
Laura Gamez-Diaz, Markus G. Seidel
Summary: CTLA-4 insufficiency, LRBA deficiency, and DEF6 deficiency present overlapping clinical phenotypes mainly attributed to defective suppressive activity of Tregs, leading to impaired immune homeostasis, increased risk of infections, autoimmune diseases, and malignancies. Successful treatment options include administration of soluble CTLA-4-Ig fusion protein, Treg cell-sparing immune suppressants, and hematopoietic stem cell transplantation.
FRONTIERS IN PEDIATRICS
(2021)
Article
Immunology
Adriana Margarit-Soler, Angela Deya-Martinez, Juan Torres Canizales, Alexandru Vlagea, Ana Garcia-Garcia, Julia Marsal, Maria Trabazo Del Castillo, Silvia Planas, Silvia Simo, Ana Esteve-Sole, Maria Suarez-Lledo Grande, Isabel Badell, Montserrat Rovira Tarrats, Francesc Fernandez-Aviles, Laia Alsina
Summary: CTLA-4 haploinsufficiency is a T-cell hyperactivation disorder that can cause immunodeficiency and immune dysregulation. HSCT is a potentially curable treatment for treatment-resistant immune dysregulation, but there is limited experience in managing complications post-HSCT.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
Worawit Louthrenoo, Nuntana Kasitanon, Antika Wongthanee, Shoji Kuwata, Fujio Takeuchi
Summary: The A allele at the +49A/G locus of the CTLA-4 gene was associated with RA in Thai patients, and was significantly higher in the subgroup of RA patients with positive RF and anti-CCP. No polymorphisms at these 4 loci were observed in SLE or SSc patients.
INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES
(2021)
Article
Medicine, General & Internal
Allison Remiker, Kristina Bolling, James Verbsky
Summary: CVID is a heterogeneous group of disorders characterized by abnormal B-cell differentiation and impaired production of specific immunoglobulin. Clinical manifestations vary and include recurrent bacterial infections, lymphoproliferation, autoimmunity, pulmonary disease, gastrointestinal disease, granulomas, and increased cancer risk. The diagnosis of CVID is complex, requiring exclusion of other causes of immunoglobulin deficiency and assessment based on clinical criteria models. Treatment involves regular immunoglobulin replacement therapy, infection prevention, and surveillance for complications.
MEDICAL CLINICS OF NORTH AMERICA
(2024)
Article
Immunology
Nima Memaran, Mareike Onnen, Carsten Mueller, Nicolaus Schwerk, Julia Carlens, Bianca Borchert-Moerlins, Elena Bauer, Ricarda Bloete, Rizky I. Sugianto, Katharina Zuern, Elke Wuehl, Gregor Warnecke, Igor Tudorache, Gesine Hansen, David W. Gjertson, Bernhard M. W. Schmidt, Anette Melk
Summary: Pediatric lung transplant recipients have a high and sustained burden of subclinical cardiovascular damage. Classical and nonclassical risk factors, such as male sex, longer time since transplantation, higher diastolic blood pressure, lower glomerular filtration rate, lower hemoglobin levels, and the presence of diabetes, are associated with increased measures of cardiovascular damage.
Article
Cardiac & Cardiovascular Systems
Felix Nagel, Anne-Kristin Schaefer, Ines Fonseca Goncalves, Eylem Acar, Andre Oszwald, Philipp Kaiser, Renate Kain, Karola Trescher, Wolf H. Eilenberg, Christine Brostjan, David Santer, Attila Kiss, Bruno K. Podesser
Summary: This study found that TNC may play an important role in the formation and progression of AAA, with TNC knockout mice showing lower disease diameters compared to wild-type mice. In human cells, TNC incubation resulted in the expression of remodeling-associated proteins.
INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY
(2022)
Article
Gastroenterology & Hepatology
Charlotte Lloyd, Jessica Leighton, Lin Lee Wong, Anna Goulding, Ann Brownlee, Penney Gray, Emma Culver, Neil Halliday, Doug Thorburn, Michael A. Heneghan, David E. J. Jones, Catherine Exley, Jessica K. Dyson
Summary: This study explored the experiences and needs of patients with autoimmune hepatitis. The findings revealed that patients require more support networks and empowerment, while also facing issues of stigma and fatigue. Patient priorities for improving care include slowing disease progression, avoiding corticosteroids, and minimizing side effects. The study also found that patients are willing to participate in clinical trials.
DIGESTIVE DISEASES AND SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Nadir Abbas, Emma L. Culver, Douglas Thorburn, Neil Halliday, Hannah Crothers, Jessica K. Dyson, April Phaw, Richard Aspinall, Salim I. Khakoo, Yiannis Kallis, Belinda Smith, Imran Patanwala, Anne McCune, Chenchu R. Chimakurthi, Vinod Hegade, Michael Orrell, Rebecca Jones, George Mells, Colette Thain, Robert-Mitchell Thain, David Jones, Gideon Hirschfield, Palak J. Trivedi
Summary: This study aimed to evaluate the effectiveness of obeticholic acid (OCA) and fibric acid derivatives as second-line treatments for primary biliary cholangitis. The study found that rates of biochemical response and drug discontinuation were similar between fibric acid derivatives and OCA in patients in the United Kingdom.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Rheumatology
Felix Kartnig, Daniel Mrak, Elisabeth Simader, Selma Tobudic, Helga Radner, Peter Mandl, Lisa Goeschl, Nikolaus Hommer, Margareta Mayer, Philipp Hofer, Thomas Hummel, Thomas Deimel, Irina Gessl, Antonia Puchner, Andreas Kerschbaumer, Renate Thalhammer, Alessandra Handisurya, Renate Kain, Stefan Winkler, Josef S. Smolen, Karin Stiasny, Thomas Perkmann, Helmuth Haslacher, Judith H. Aberle, Daniel Aletaha, Leonhard X. Heinz, Daniela Sieghart, Michael Bonelli
Summary: This clinical trial evaluated the immunogenicity and safety of a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMIDs). The results showed that the third vaccination had good immunogenicity and safety in these patients, but the effects of immunomodulatory therapy should be considered.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Alan Kennedy, Maximillian A. Robinson, Claudia Hinze, Erin Waters, Cayman Williams, Neil Halliday, Simon Dovedi, David M. Sansom
Summary: CTLA-4 and PD-1 are immune checkpoint receptors targeted in cancer treatment. A recent discovery shows that the interaction between their respective ligands, CD80 and PD-L1, can block PD-L1/PD-1 binding and inhibit PD-L1 functions. The internalization of CD80 results in the recovery of PD-L1 availability, while CD80/PD-L1 complexes remain on the plasma membrane. CTLA-4 modulates PD-L1:PD-1 interactions by controlling CD80.
Article
Immunology
Daniel Mrak, Felix Kartnig, Daniela Sieghart, Elisabeth Simader, Helga Radner, Peter Mandl, Lisa Goeschl, Philipp Hofer, Thomas Deimel, Irina Gessl, Renate Kain, Stefan Winkler, Josef S. Smolen, Thomas Perkmann, Helmuth Haslacher, Daniel Aletaha, Leonhard X. Heinz, Michael Bonelli
Summary: A study found that patients under immunosuppression experienced a rapid decline in antibodies after the third COVID-19 vaccine dose, and it remains unclear whether immunosuppressive therapy affects immune responses. Monitoring the immune response and adverse events in 50 immunosuppressed patients and 42 healthy controls, it was observed that immunosuppressed patients had significantly lower antibody levels, suggesting the need for an early fourth vaccination.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Gastroenterology & Hepatology
Ji Jade King, Neil Halliday, Anna Mantovani, Alessio Gerussi, Emmanuel Q. Wey, Jaclyn Tan, Jennifer Ryan, David Patch, Emmanuel Tsochatzis, Rachel H. Westbrook
Summary: Spontaneous bacterial peritonitis (SBP) is a serious clinical condition with a poor prognosis. The prevalence, microbiological flora, and prognostic significance of bacterascites (BA) are not well understood. This study compared the prognosis and outcomes of patients with BA and SBP, and found that SBP patients had higher mortality rates at 1 and 3 months compared to BA patients. However, there was no significant difference in survival between the two groups after 6 months. BA has a negative impact on patient survival and should be considered as a poor prognostic marker.
LIVER TRANSPLANTATION
(2023)
Article
Hematology
Nyamdelger Sukhbaatar, Maria Schoeller, Stephanie Deborah Fritsch, Monika Linke, Stefanie Horer, Manuela Traeger, Mario Mazic, Stephan Forisch, Karine Gonzales, Jan Pascal Kahler, Carina Binder, Caroline Lassnig, Birgit Strobl, Mathias Mueller, Barbara Scheiber-Mojdehkar, Claudia Gundacker, Stefanie Dabsch, Renate Kain, Markus Hengstschlaeger, Steven H. L. Verhelst, Guenter Weiss, Igor Theurl, Thomas Weichhart
Summary: Iron is a crucial cellular metal for various physiological functions. Its absorption from the diet and transport by transferrin is important for iron metabolism. Regulation of iron absorption and transfer remains poorly understood. In this study, macrophage-specific deletion of Tsc2, a negative regulator of mTORC1, in mice led to defects in iron metabolism, including impaired erythropoiesis and reduced Tf saturation. This was due to an iron import block in the duodenal epithelial cells. Activation of mTORC1 in duodenal macrophages promoted Tf degradation, while depletion of macrophages increased Tf levels. Inhibition of mTORC1 or serine protease activity restored Tf levels in the Tsc2-deficient mice. These findings suggest that duodenal macrophages regulate iron transfer by controlling Tf availability.
Article
Virology
Ellen Gelpi, Sigrid Klotz, Miriam Beyerle, Sven Wischnewski, Verena Harter, Harald Kirschner, Katharina Stolz, Christoph Reisinger, Elisabeth Lindeck-Pozza, Alexander Zoufaly, Marlene Leoni, Gregor Gorkiewicz, Martin Zacharias, Christine Haberler, Johannes Hainfellner, Adelheid Woehrer, Simon Hametner, Thomas Roetzer, Till Voigtlaender, Gerda Ricken, Verena Endmayr, Carmen Haider, Judith Ludwig, Andrea Polt, Gloria Wilk, Susanne Schmid, Irene Erben, Anita Nguyen, Susanna Lang, Ingrid Simonitsch-Klupp, Christoph Kornauth, Maja Nackenhorst, Johannes Klaeger, Renate Kain, Andreas Chott, Richard Wasicky, Robert Krause, Guenter Weiss, Judith Loeffler-Rag, Thomas Berger, Patrizia Moser, Afshin Soleiman, Martin Asslaber, Roland Sedivy, Nikolaus Klupp, Martin Klimpfinger, Daniele Risser, Herbert Budka, Lucas Schirmer, Anne-Katrin Probstel, Romana Hoeftberger
Summary: We conducted a neuropathological analysis on 32 patients who died from COVID-19 in Austria between 2020 and 2021. The results showed diffuse white matter damage and microglial activation in all cases, indicating indirect brain damage rather than direct virus-specific damage. Inflammatory changes and vascular pathologies were also observed, along with silent neurodegenerative pathologies in elderly patients. These findings align with experimental data on SARS-CoV-2-related brain damage and provide a better understanding of the mechanisms underlying neurological symptoms after COVID-19.
Article
Genetics & Heredity
Sophie H. H. Schmidt, Ursula Barnas, Christof Aigner, Peter Wolf, Nicolas Kozakowski, Renate Kain, Thomas Scherer, Alice Schmidt, Gere Sunder-Plassmann
Summary: A 24-year-old man with diabetes mellitus and severe proteinuria was diagnosed with ABCC8-MODY12. Kidney biopsy showed nodular glomerulosclerosis. Dialysis and treatment with a sulfonylurea improved his glycemic control. This case highlights the risk of early-onset and severe diabetic kidney disease in patients with ABCC8-MODY12 and emphasizes the importance of timely genetic diagnosis for proper treatment and prevention of late sequelae of diabetes.
FRONTIERS IN GENETICS
(2023)
Article
Peripheral Vascular Disease
Rizky I. Sugianto, Carl Grabitz, Aysun Bayazit, Ali Duzova, Daniela Thurn-Valsassina, Nima Memaran, Anke Doyon, Nur Canpolat, Ipek Kaplan Bulut, Karolis Azukaitis, Lukasz Obrycki, Ali Anarat, Rainer Buescher, Salim Caliskan, Jerome Harambat, Francesca Lugani, Zeynep B. Ozcakar, Dusan Paripovic, Bruno Ranchin, Uwe Querfeld, Franz Schaefer, Bernhard M. W. Schmidt, Anette Melk
Summary: The effect of blood pressure control on left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH) was assessed. Stricter blood pressure control led to regression of LVMI and LVH.
Article
Urology & Nephrology
Andre Oszwald, Raul A. Mejia-Pedroza, Helga Schachner, Christof Aigner, Andrew Rees, Renate Kain
Summary: The study used the DSP platform to analyze protein and mRNA expression in biopsies from patients with piFNGN, revealing gene expression profiles that are related to the morphological evolution of glomerular injury.
Article
Cell Biology
Birgit Hoeger, Wiebke Nadolni, Sarah Hampe, Kilian Hoelting, Marco Fraticelli, Nadja Zaborsky, Anna Madlmayr, Viktoria Sperrer, Laura Fraticelli, Lynda Addington, Dirk Steinritz, Vladimir Chubanov, Roland Geisberger, Richard Greil, Andreas Breit, Ingrid Boekhoff, Thomas Gudermann, Susanna Zierler
Summary: This study identifies TRPM7 kinase as a key regulator of AKT-driven COX-2 expression and suggests the potential therapeutic significance of TRPM7 blockade in COX-2-related inflammation and malignancy.