Review
Immunology
Erica A. Steen, Kim E. Nichols, Lauren K. Meyer
Summary: Familial hemophagocytic lymphohistiocytosis (fHLH) is a group of rare inherited immune dysregulation disorders characterized by mutations in genes involved in cytotoxic granules in CD8+ T cells and NK cells. This defect leads to sustained lymphocyte activation and excessive secretion of pro-inflammatory cytokines, resulting in tissue damage and multi-organ failure. Studies in murine models have provided insights into the mechanisms underlying hyperinflammation in fHLH.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Vandana Chaturvedi, Rebecca A. Marsh, Adi Zoref-Lorenz, Erika Owsley, Vijaya Chaturvedi, Trung C. Nguyen, Jordana R. Goldman, Michael M. Henry, Jay N. Greenberg, Stephan Ladisch, Michelle L. Hermiston, Michael Jeng, Ahmed Naqvi, Carl E. Allen, Hector R. Wong, Michael B. Jordan
Summary: Hemophagocytic lymphohistiocytosis (HLH) is characterized by acute T-cell activation, with CD38(high)/HLA-DR+ effector cells being most pronounced. In contrast, sepsis does not show this distinctive T-cell activation. CD38(high)/HLA-DR+ cells concentration above 7% has strong predictive value for distinguishing HLH from early sepsis or healthy controls.
Article
Allergy
Josee-Anne Joly, Alexis Vallee, Benoite Bourdin, Sara Bourbonnais, Natalie Patey, Louis Gaboury, Yves Theoret, Helene Decaluwe
Summary: This study found that the combination of IFN-y blockade and JAK 1/2 inhibitor ruxolitinib can effectively suppress disease progression in familial hemophagocytic lymphohistiocytosis (HLH).
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Xiang Liu, Xueling Zhu, Xiaotang Zhou, Yirui Xie, Dairong Xiang, Zhikai Wan, Ying Huang, Biao Zhu
Summary: This study describes two cases of AIDS-related secondary HLH treated with ruxolitinib. The results highlight the feasibility of using ruxolitinib as a first-line therapy in patients with HIV infection and secondary HLH. However, the safety and efficacy of this novel treatment need to be evaluated in large clinical trials in the future.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Erica A. Steen, Michelle L. Hermiston, Kim E. Nichols, Lauren K. Meyer
Summary: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder caused by mutations in genes necessary for cytotoxic granule assembly and function, leading to ineffective immune responses. The resulting persistent immune system stimulation drives severe tissue inflammation and end-organ damage. Evidence supports a potential digenic mode of inheritance, where mutations in two different genes cooperate to impair pathway activity.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Michael B. Jordan
Summary: HLH is an immune system disorder that has seen advancements in diagnosis and treatment in recent decades. It is characterized by excessive T cell activation and myeloid cell activation, largely driven by interferon-gamma. Diagnosis and treatment now rely on measuring T cell activation, IFN-gamma activity, and inflammation.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Immunology
Madhura G. Kelkar, Umair Ahmad Bargir, Reetika Malik-Yadav, Maya Gupta, Aparna Dalvi, Neha Jodhawat, Shweta Shinde, Manisha R. Madkaikar
Summary: The study found that CD8+ cytotoxic T lymphocytes from HLH patients exhibited high expression of exhaustion markers with overall impaired function. This is the first report suggesting functional exhaustion of CD8 T cells in both primary and secondary HLH. Further research is needed to understand the association between exhaustion and disease outcome for potential therapeutic implementation.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Solene La Marle, Gaelle Richard-Colmant, Mathieu Fauvernier, Herve Ghesquieres, Arnaud Hot, Pascal Seve, Yvan Jamilloux
Summary: This study used multiple-cause-of-death analysis to investigate the mortality and associated causes of Hemophagocytic lymphohistiocytosis (HLH). Between 2000 and 2016, HLH was mentioned in 2072 death certificates, with 232 cases as the underlying cause of death and 1840 cases as a non-underlying cause of death. The age-standardized mortality rate of HLH was 1.93 per million person-years and showed an increasing trend over the study period. HLH decedents were more likely to have associated CMV infections or hematological diseases compared to the general population.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Immunology
Xin Huang, Bingxuan Wu, Di Wu, Xiaoming Huang, Min Shen
Summary: Haploinsufficiency of GATA2, also known as GATA2 deficiency, can result in a wide range of clinical manifestations. In this study, we presented a case of a 28-year-old male with a GATA2 variant who also suffered from hemophagocytic lymphohistiocytosis (HLH), ultimately diagnosed as HLH triggered by Mycobacterium avium bloodstream infection due to primary immunodeficiency. We also reviewed GATA2 deficiency patients with HLH and found that GATA2 variants causing loss of zinc finger domains were associated with HLH, with erythema nodosum possibly being an accompanying symptom.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biophysics
Ditta Ungor, Anna Barbasz, Agnieszka Czyzowska, Edit Csapo, Magdalena Ocwieja
Summary: This study focused on the comparative cytotoxicity investigations of protein-stabilized gold nanoclusters on lymphocytes B and T cells. It was found that gamma G-Au NCs induced the highest disorders in mitochondrial activity, while LYZ- and gamma G-Au NCs enhanced the secretion of malonic dialdehyde. Despite minor effects on cell viability, all Au NCs caused oxidative stress and could stimulate undesirable cellular processes.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2021)
Article
Biology
Daniel D. Reiff, Mingce Zhang, Randy Q. Cron
Summary: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by uncontrolled inflammation and immune system activation. Primary HLH (pHLH) is caused by genetic mutations that lead to organ failure and can be fatal. Secondary HLH (sHLH) can be triggered by genetic mutations in certain genes. This study focused on the significance of a DOCK2 mutation in the pathogenesis of sHLH and its implications for diagnosis and treatment.
Article
Immunology
Timo C. E. Zondag, Lamberto Torralba-Raga, Jan A. M. Van Laar, Maud A. W. Hermans, Arjen Bouman, Iris H. I. M. Hollink, P. Martin Van Hagen, Deborah A. Briggs, Alistair N. Hume, Yenan T. Bryceson
Summary: This study reports a new RAB27A variant in a 35-year old male patient with hemophagocytic lymphohistiocytosis. The variant affected certain cellular functions but did not have an impact on appearance and pigmentation. Further investigation revealed altered binding affinity to key effector proteins, potentially leading to impaired immune cell function.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Pediatrics
Niveditha Balakumar, Prithvi Sendi, Balagangadhar R. Totapally
Summary: This study describes the prevalence, clinical characteristics, interventions, and outcomes of neonates diagnosed with hemophagocytic lymphohistiocytosis (HLH) in the United States. It found that HLH is a rare diagnosis with a high mortality rate in neonates. Herpes simplex virus is the most common infection associated with neonatal HLH, and HLH should be considered in neonates presenting with multi-organ dysfunction or sepsis.
FRONTIERS IN PEDIATRICS
(2022)
Article
Immunology
William R. Otto, Edward M. Behrens, David T. Teachey, Daryl M. Lamson, David M. Barrett, Hamid Bassiri, Michelle P. Lambert, Suzanne Mount, Whitney L. Petrosa, Neil Romberg, Kathleen E. Sullivan, Alexis A. Topjian, Brian T. Fisher, Adriana E. Kajon
Summary: This study describes 5 children who developed HLH or HLH-like illness after adenovirus type 7 infection, without genetic predisposition. All patients recovered, suggesting that adenovirus 7 infection alone can result in HLH.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Critical Care Medicine
Sandrine Valade, Gregoire Monseau, Eric Mariotte, Michael Darmon
Summary: The study aimed to assess features mimicking hemophagocytic syndrome in critically ill hematologic patients using diagnostic scores. Results indicate that both HScore and hemophagocytic lymphohistiocytosis criteria are highly accurate in identifying hemophagocytic syndrome in ICU patients, despite potential confounding factors.
CRITICAL CARE MEDICINE
(2021)
Article
Immunology
Muskan Israni, Bethany Nicholson, Nizar Mahlaoui, Laura Obici, Linda Rossi-Semerano, Helen Lachmann, Georgia Hayward, Mojca Zajc Avramovic, Aurelien Guffroy, Virgil Dalm, Rachel Rimmer, Leire Solis, Carlotta Villar, Andrew R. Gennery, Stephanie Skeffington, Julia Nordin, Klaus Warnatz, Anne-Sophie Korganow, Jordi Anton, Marco Cattalini, Tania Amin, Stephan Berg, Pere Soler-Palacin, Siobhan O. Burns, Mari Campbell
Summary: This study aims to understand the prevalence and practice of transition services for young people with IEI in Europe. The survey results showed that almost all services transitioned patients to adult services, but there is a lack of standardized guidelines.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Mikael Hakkola, Pekka Vehvilaeinen, Janita Muotka, Mysore V. Tejesvi, Tytti Pokka, Paeivi Vaehaesarja, Anna-Maija Hanni, Marjo Renko, Matti Uhari, Jarmo Salo, Terhi Tapiainen
Summary: The mechanism by which cranberry-lingonberry juice (CLJ) prevents urinary tract infections (UTI) in children remains unknown. This study found that children who consumed CLJ had a lower abundance of Proteobacteria and a higher abundance of Firmicutes phylum in their urinary microbiome at 3 months than those in the placebo group. In the gut microbiome, the abundance of Actinobacteria was higher in children receiving CLJ. A healthy urinary microbiome may be important in preventing UTIs in children.
Article
Immunology
Elina A. Tuovinen, Outi Kuismin, Leila Soikkonen, Timi Martelius, Meri Kaustio, Sari Hamalainen, Hanna Viskari, Jaana Syrjanen, Ulla Wartiovaara-Kautto, Kari K. Eklund, Janna Saarela, Markku Varjosalo, Juha Kere, Timo Hautala, Mikko R. J. Seppanen
Summary: The NF-κB family of transcription factors is important in cellular signaling pathways, and NFKB1 variants have been associated with CVID and immunodeficiency. However, the penetrance and prevalence of CVID are relatively low, while inflammatory manifestations are more common.
CLINICAL IMMUNOLOGY
(2023)
Review
Allergy
Stuart G. Tangye
Summary: Since the emergence of SARS-CoV-2 in December 2019, the COVID-19 pandemic has resulted in over 6.5 million deaths worldwide, highlighting the crucial role of the immune system in defending against emerging pathogens. Inborn errors of immunity (IEI), characterized by defects in immune cell development and function, make individuals highly susceptible to severe infections and immune dysregulation. The study of IEI has provided valuable insights into the mechanisms of disease pathogenesis and immunopathology, which can inform the development of therapies for both emerging and established infectious diseases.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Pediatrics
Jenni Turunen, Niko Paalanne, Justus Reunanen, Terhi Tapiainen, Mysore V. Tejesvi
Summary: This study found that the composition of the gut mycobiome in infants is influenced by the mode of delivery and exposure to intrapartum antibiotics.
PEDIATRIC RESEARCH
(2023)
Editorial Material
Immunology
Timi Martelius, Mikko R. J. Seppanen, Klaus Warnatz
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Sevgi Kostel Bal, Sarah Giuliani, Jana Block, Peter Repiscak, Christoph Hafemeister, Tala Shahin, Nurhan Kasap, Bernhard Ransmayr, Yirun Miao, Cheryl van de Wetering, Alexandra Frohne, Raul Jimenez Heredia, Michael Schuster, Samaneh Zoghi, Vanessa Hertlein, Marini Thian, Aleksandr Bykov, Royala Babayeva, Sevgi Bilgic Eltan, Elif Karakoc-Aydiner, Lisa E. Shaw, Iftekhar Chowdhury, Markku Varjosalo, Rafael J. Arguello, Matthias Farlik, Ahmet Ozen, Edgar Serfling, Loic Dupre, Christoph Bock, Florian Halbritter, J. Thomas Hannich, Irinka Castanon, Michael J. Kraakman, Safa Baris, Kaan Boztug
Summary: In this study, the researchers investigated the role of NFATC1 mutations in human immunity and found evidence of metabolic plasticity in patient T cells. The study also demonstrated that metformin and rosiglitazone can improve the effector functions of patient T cells.
Article
Oncology
Stine Gahr, Giovanna Perinetti Casoni, Maren Falk-Paulsen, Gregor Maschkowitz, Yenan T. Bryceson, Matthias Voss
Summary: This study found that pathogenic variants of SAMD9/SAMD9L genes can be modulated by viral host range factors M062, C7, and K1 through molecular interactions. Among them, K1 displayed the greatest potency and almost completely restored cellular proliferation and translation. This study provides a new opportunity for therapeutic modulation of these pathogenic gene variants and also provides insights into the complex intramolecular regulation of SAMD9/SAMD9L activity.
EXPERIMENTAL CELL RESEARCH
(2023)
Editorial Material
Allergy
Timi Martelius, Mikko R. J. Seppanen
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Paulina Staus, Stephan Rusch, Sabine El-Helou, Gabriele Mueller, Mate Krausz, Ulf Geisen, Andres Caballero-Oteyza, Renate Krueger, Shahrzad Bakhtiar, Min Ae Lee-Kirsch, Maria Fasshauer, Ulrich Baumann, Bimba Franziska Hoyer, Joao Farela Neves, Michael Borte, Maria Carrabba, Fabian Hauck, Stephan Ehl, Peter Bader, Horst von Bernuth, Faranaz Atschekzei, Mikko R. J. Seppaenen, Klaus Warnatz, Alexandra Nieters, Gerhard Kindle, Bodo Grimbacher
Summary: Patient registries are important for studying rare diseases, and the GAIN consortium developed a dataset to address the challenges of multi-organ autoimmunity and autoinflammation. The dataset includes information on genetics, phenotypes, medication, and laboratory values. Twelve European centers have registered 419 patients with these conditions, providing a valuable resource for research.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Wenny Santaniemi, Pirjo Astrom, Virpi Glumoff, Nora Pernaa, Ella-Noora Tallgren, Sanna Palosaari, Antti Nissinen, Meri Kaustio, Outi Kuismin, Janna Saarela, Katariina Nurmi, Kari K. Eklund, Mikko R. J. Seppanen, Timo Hautala
Summary: In this study, the impact of a heterozygous NFKB1 c.C936T/p.R157X LOF variant on immunity in sterile fasciitis patients and their family members was explored. The variant resulted in reduced p50 or p105 protein levels and elevated IL-1 beta and IL-8 levels, potentially contributing to the high neutrophil counts observed during fasciitis episodes. The variant also led to reduced phosphorylation of p65/RelA in neutrophils, suggesting defective activation of canonical NF-kappa B, and compromised oxidative burst following activation of NF-kappa B-dependent mechanisms.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Laurent Schmied, Thuy T. Luu, Jonas N. Sondergaard, Sophia H. Hald, Stephan Meinke, Dara K. Mohammad, Sunitha B. Singh, Corinna Mayer, Giovanna Perinetti Casoni, Michael Chrobok, Heinrich Schlums, Giorgia Rota, Hieu M. Truong, Lisa S. Westerberg, Greta Guarda, Evren Alici, Arnika K. Wagner, Nadir Kadri, Yenan T. Bryceson, Mezida B. Saeed, Petter Hoglund
Summary: Natural killer (NK) cells recognize infected cells and tumors. The function of NK cells depends on balanced signaling from activating and inhibitory receptors. The subcellular localization of tyrosine phosphatase SHP-1 determines NK cell tolerance and education. Education of NK cells leads to reduced synapse accumulation of SHP-1 and augmented signaling from activating receptors.
Article
Medicine, General & Internal
Pia Holma, Paula Pesonen, Minna K. Karjalainen, Marjo-Riitta Jaervelin, Sara Vaeyrynen, Eeva Sliz, Anni Heikkilae, Mikko R. J. Seppaenen, Johannes Kettunen, Juha Auvinen, Timo Hautala
Summary: Smoking and genetic variation (FCGR2B and TNFRSF13B) were found to be the most important factors determining serum IgG concentration. The study also found that low serum IgG was associated with antibiotic use and sinus surgery, while high serum IgG was associated with pneumonia incidence and total number of pneumonia episodes.
Article
Microbiology
Mysore V. Tejesvi, Jenni Turunen, Sonja Salmi, Justus Reunanen, Niko Paalanne, Terhi Tapiainen
Summary: Exposure to antibiotics at birth and Caesarean section delivery both affect the development of infant gut bacteriome. In this study, the relationships between bacteria and fungi in the gut microbiome of 140 infants from birth to 18 months were investigated. It was found that perinatal factors, delivery mode and intrapartum antibiotic exposure influenced the associations between bacterial and fungal species.
Article
Computer Science, Interdisciplinary Applications
Rasmus Ryyppo, Sergei Hayrynen, Henry Joutsijoki, Martti Juhola, Mikko R. J. Seppanen
Summary: Machine learning can successfully predict the occurrence of rare diseases in patients at least 30 days before the initial diagnosis, and a performative custom deep learning model can be built.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2024)