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)
Editorial Material
Clinical Neurology
Giorgia Bucciol, Nele Willemyns, Benjamin Verhaaren, Xavier Bossuyt, Katrien Lagrou, Anniek Corveleyn, Despina Moshous, Katrien Jansen, Liesbeth De Waele, Isabelle Meyts
Summary: Encephalitis and encephalopathy in children pose a diagnostic challenge. This case report highlights the importance of considering hemophagocytic lymphohistiocytosis (HLH) as a differential diagnosis, especially in isolated central nervous system forms. Inborn errors of immunity may underlie isolated encephalitis, and should be included in the differential diagnosis for these presentations.
Article
Immunology
Yifan He, Yun Hui, Haibo Liu, Yifan Wu, Hong Sang, Fang Liu
Summary: This article presents a patient who developed HLH after receiving a COVID-19 vaccine, emphasizing the need for caution in individuals with preexisting immune dysregulation or diseases not classified when receiving the vaccine. A review of genetic defects and cutaneous manifestations of HLH was also conducted.
Article
Immunology
Dan Tomomasa, Eitaro Hiejima, Takayuki Miyamoto, Kay Tanita, Masaki Matsuoka, Daiki Niizato, Noriko Mitsuiki, Takeshi Isoda, Takahiro Yasumi, Menno C. van Zelm, Tomohiro Morio, Hirokazu Kanegane
Summary: Familial hemophagocytic lymphohistiocytosis type 3 is a fatal inborn error of immunity caused by abnormal cytotoxic activity of T and NK cells, resulting from variants in the UNC13D gene. This study reports two cases with the exact same tandem duplication breakpoints in the UNC13D gene, along with other related analyses.
CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Daiki Niizato, Takeshi Isoda, Noriko Mitsuiki, Shuya Kaneko, Dan Tomomasa, Takahiro Kamiya, Masatoshi Takagi, Kohsuke Imai, Michiko Kajiwara, Masaki Shimizu, Tomohiro Morio, Hirokazu Kanegane
Summary: This case report describes a new treatment approach for familial hemophagocytic lymphohistiocytosis (FHL). The study used cytokine profiles as a guide and administered dose-adjusted ruxolitinib as a bridging therapy, successfully preparing the patient for hematopoietic cell transplantation (HCT). The results demonstrate the effectiveness and safety of this treatment approach and highlight the importance of monitoring specific cytokine levels.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pediatrics
Taro Yoshida, Kunihiko Moriya, Keisuke Oikawa, Shoko Miura, Yoshiko Asakura, Sachiko Tanifuji, Shuji Kusano, Mikiya Endo, Manami Akasaka
Summary: Familial hemophagocytic lymphohistiocytosis (FHL) is a severe genetic immune disorder that impairs the function of certain immune cells. This case report highlights a rare presentation of FHL3 with cerebellar swelling and obstructive hydrocephalus. Despite treatment, the patient did not respond and ultimately died. Early diagnosis of FHL, especially for cases with atypical symptoms, is crucial for better outcomes.
FRONTIERS IN PEDIATRICS
(2022)
Article
Immunology
Julia E. Segal, Jessica D. Daley, Jessie L. Barnum, Claudia M. Salgado, Miguel Reyes-Mugica, Corinne Schneider, Serter Gumus, Darshit Thakrar, Steven W. Allen, Scott W. Canna
Summary: This case report illustrates HLH foci presenting as pulmonary/renal nodules, demonstrates the importance of monitoring a range of HLH biomarkers, and suggests the potential benefit of earlier initiation of salvage therapy.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Yue Yang, Zebin Luo, Tianming Yuan
Summary: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare but potentially fatal disease, with timely diagnosis being a challenge. This case report of FHL type 3 presenting in the early neonatal period highlights thrombocytopenia as a possible early sign, emphasizing the importance of genetic testing and prompt diagnosis confirmation.
Article
Medicine, General & Internal
Clara Baverez, Maximilien Grall, Mathieu Gerfaud-Valentin, Sarah De Gail, Alexandre Belot, Thomas Perpoint, Emmanuelle Weber, Quitterie Reynaud, Pascal Seve, Yvan Jamilloux
Summary: Anakinra is an effective and safe treatment for secondary HLH, showing rapid symptom relief and reduction of inflammatory markers. Further prospective randomized clinical trials are needed to confirm its efficacy.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Immunology
Snehal Shabrish, Madhura Kelkar, Reetika Malik Yadav, Umair Ahmed Bargir, Maya Gupta, Aparna Dalvi, Jahnavi Aluri, Manasi Kulkarni, Shweta Shinde, Sneha Sawant-Desai, Priyanka Kambli, Gouri Hule, Priyanka Setia, Neha Jodhawat, Pallavi Gaikwad, Amruta Dhawale, Nayana Nambiar, Vijaya Gowri, Ambreen Pandrowala, Prasad Taur, Revathi Raj, Ramya Uppuluri, Ratna Sharma, Pranoti Kini, Meena Sivasankaran, Deenadayalan Munirathnam, Ramprasad Vedam, Pandiarajan Vignesh, Aaqib Banday, Amit Rawat, Amita Aggarwal, Ujjal Poddar, Meenakshi Girish, Abhijit Chaudhary, Abhilasha Sampagar, Dharani Jayaraman, Narendra Chaudhary, Nitin Shah, Farah Jijina, S. Chandrakla, Swati Kanakia, Brijesh Arora, Santanu Sen, Madhukar Lokeshwar, Mukesh Desai, Manisha Madkaikar
Summary: Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation and systemic inflammation. In India, FHL2 and FHL3 are the most common subtypes. Genetic heterogeneity in the Indian population and poor prognosis of FHL were confirmed in this study, emphasizing the importance of flow cytometry-based assays in rapid diagnosis and validation of novel variants.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pediatrics
Payman Sadeghi, Golnaz Ghazizadeh Esslami, Hassan Rokni-Zadeh, Majid Changi-Ashtiani, Reihaneh Mohsenipour
Summary: This report presented two cases of Hemophagocytic lymphohistiocytosis (HLH) with different presentations. The genetic testing revealed that both patients had mutations in the UNC13D gene, associated with Familial Hemophagocytic Lymphohistiocytosis 3 (FHL3). The research suggests that sequencing of the entire UNC13D gene is a useful diagnostic procedure for atypical manifestations of HLH.
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Wei Wang, Xu Yang, Jigang Yang
Summary: An 18-year-old man with familial HLH underwent FDG PET/CT which showed abnormalities in the brain, liver, and lymph nodes. After chemotherapy, a follow-up FDG PET/CT revealed no abnormal F-18-FDG activity, indicating a complete response. This case suggests that FDG PET/CT can be useful not only in staging familial HLH but also in evaluating therapy response.
CLINICAL NUCLEAR MEDICINE
(2021)
Review
Immunology
Camille Keenan, Kim E. Nichols, Sabrin Albeituni
Summary: Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome driven by overactive T cells and macrophages that abundantly secrete pro-inflammatory cytokines. Etoposide-based regimens have reduced mortality associated with HLH, but the 5-year survival rate remains low. Novel cytokine-directed therapies, such as ruxolitinib, are being studied to improve outcomes in HLH.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pediatrics
Juhi Gupta, Prashant Jauhari, Atin Kumar, Sheffali Gulati, Biswaroop Chakrabarty, Aditya Kumar Gupta, Rachna Seth
Summary: Primary hemophagocytic lympho-histiocytosis (HLH) is a hyperinflammatory syndrome that can mimic other diseases in the central nervous system (CNS). This case report describes a 7-year-old boy who initially presented with symptoms suggestive of CNS tuberculosis and later had a diagnosis of acquired demyelination syndrome, but was ultimately found to have primary HLH. The delayed diagnosis highlights the importance of considering HLH as a possible cause of refractory demyelination.
Review
Pharmacology & Pharmacy
Dragan Primorac, Martin Cemerin, Vid Matisic, Vilim Molnar, Marko Strbad, Lenart Girandon, Lucija Zenic, Miomir Knezevic, Stephen Minger, Denis Polancec
Summary: The COVID-19 pandemic has had a significant impact globally and the overaggressive immune reaction in response to the virus can lead to ARDS. Mesenchymal stromal cell therapy presents a potential treatment option for severe patients.
Article
Pediatrics
Egle Kvedaraite, Magda Lourda, HongYa Han, Bianca Tesi, Jenee Mitchell, Maja Idestrom, Natalia Mouratidou, George Rassidakis, Tatiana von Bahr Greenwood, Fleur Cohen-Aubart, Martin Jadersten, Selma Olsson Akefeldt, Mattias Svensson, George Kannourakis, Yenan T. Bryceson, Julien Haroche, Jan-Inge Henter
Summary: This study presented the first case series of patients with both Langerhans cell histiocytosis (LCH) and Crohn's disease (CD), highlighting diagnostic challenges and elevated IL-23 levels in LCH patients, with a correlation between lesional LCH cells and circulating IL-23 levels. Both CD and LCH should be considered in patients with inflammatory gastrointestinal involvement, with the IL-23 pathway being a common immunological trait between these two granulomatous diseases.
Letter
Hematology
Monika Klimkowska, Yasuhito Nannya, Charlotte Gran, Robert Mansson, Iyadh Douagi, Seishi Ogawa, Hareth Nahi, Magnus Tobiasson
Article
Rheumatology
AnnaCarin Horne, Tatiana von Bahr Greenwood, Samuel C. C. Chiang, Marie Meeths, Caroline Bjorklund, Maria Ekelund, Peter Erensjo, Stefan Berg, Stefan Hagelberg, Yenan T. Bryceson, Ulf Andersson, Jan-Inge Henter
Summary: Moderately dosed etoposide demonstrated effectiveness in treating severe MAS-HLH, with all children responding well and surviving at latest follow-up. Some children showed improvement in neurological symptoms after treatment.
JOURNAL OF RHEUMATOLOGY
(2021)
Letter
Allergy
Andri Lemarquis, Tessa Campbell, Maribel Aranda-Guillen, Viktoria Hennings, Petter Brodin, Olle Kampe, Kaj Blennow, Henrik Zetterberg, Christine Wenneras, Kristina Eriksson, Nils Landegren, Yenan Bryceson, Stefan Berg, Olov Ekwall
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Review
Immunology
Vanessa Sancho-Shimizu, Petter Brodin, Aurelie Cobat, Catherine M. Biggs, Julie Toubiana, Carrie L. Lucas, Sarah E. Henrickson, Alexandre Belot, Stuart G. Tangye, Joshua D. Milner, Michael Levin, Laurent Abel, Dusan Bogunovic, Jean-Laurent Casanova, Shen-Ying Zhang
Summary: MIS-C, a newly emerging syndrome in children associated with COVID-19, shows heterogeneity resembling KD, possibly triggered by viruses and potentially linked to rare inborn errors of immunity altering the immune response. Discovery of monogenic IEIs underlying MIS-C may pave the way for a new genetic approach to classic KD.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Letter
Hematology
Jan-Inge Henter, Egle Kvedaraite, Daniel Martin Munoz, Monica Cheng Munthe-Kaas, Bernward Zeller, Tove A. Nystad, Caroline Bjorklund, Isabella Donner, Magda Lourda, Henrik Zetterberg, Kaj Blennow, Nikolas Herold, Desiree Gavhed, Tatiana von Bahr Greenwood
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Nutrition & Dietetics
Monika Stompor-Goracy, Agata Bajek-Bil, Maciej Machaczka
Summary: Chrysin is a natural polyphenol compound found in honey, propolis, and fruits, with various health benefits. However, its low bioavailability has led to efforts to increase its absorption and therapeutic efficacy through functionalization.
Letter
Oncology
Audrone Muleviciene, Takuya Sekine, Timo Zondag, Yenan T. Bryceson, Bianca Tesi, Jelena Rascon
PEDIATRIC BLOOD & CANCER
(2022)
Review
Immunology
Hannes Lindahl, Yenan T. Bryceson
Summary: The development of high-throughput sequencing has advanced the understanding of genotype-phenotype correlations in congenital diseases. Neuroinflammatory diseases, although rare, are increasingly recognized among inborn errors of immunity and can have a significant impact on patient care. This review focuses on the signs and symptoms of neuroinflammation associated with pathogenic variants in immune genes and proposes a subdivision based on underlying mechanisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Malin Sveijer, Tatiana von Bahr Greenwood, Martin Jadersten, Egle Kvedaraite, Henrik Zetterberg, Kaj Blennow, Magda Lourda, Desiree Gavhed, Jan-Inge Henter
Summary: This study compared levels of NFL in plasma and cerebrospinal fluid of patients with LCH, suggesting that p-NFL may be used for screening of ND-CNS-LCH. Further research is encouraged to explore the role of p-NFL in monitoring ND-CNS-LCH.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Letter
Biochemistry & Molecular Biology
Petter Brodin, Giorgio Casari, Liam Townsend, Cliona O'Farrelly, Ivan Tancevski, Judith Loeffler-Ragg, Trine H. Mogensen, Jean Laurent Casanova
Review
Immunology
Carl Inge Edvard Smith, Rula Zain, Anders osterborg, Marzia Palma, Marcus Buggert, Peter Bergman, Yenan Bryceson
Summary: The scarcity of plasmacytoid dendritic cells (pDCs) in patients with chronic lymphocytic leukaemia (CLL) may contribute to the severe clinical course of COVID-19 in these patients. Treatment of CLL with Bruton's tyrosine kinase (BTK) inhibitors can increase the number of pDCs.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Tessa Mollie Campbell, Zhiyong Liu, Qian Zhang, Marcela Moncada-Velez, Laura E. Covill, Peng Zhang, Ilad Alavi Darazam, Paul Bastard, Lucy Bizien, Giorgia Bucciol, Sara Lind Enoksson, Emmanuelle Jouanguy, Semsi Nur Karabela, Taushif Khan, Yasemin Kendir-Demirkol, Andres Augusto Arias, Davood Mansouri, Per Marits, Nico Marr, Isabelle Migeotte, Leen Moens, Tayfun Ozcelik, Isabelle Pellier, Anton Sendel, Sevtap Senoglu, Mohammad Shahrooei, C. I. Edvard Smith, Isabelle Vandernoot, Karen Willekens, Kadriye Kart Yasar, Peter Bergman, Laurent Abel, Aurelie Cobat, Jean-Laurent Casanova, Isabelle Meyts, Yenan T. Bryceson
Summary: IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-beta and compensatory adaptive immunity.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Qian Zhang, Daniela Matuozzo, Jeremie Le Pen, Danyel Lee, Leen Moens, Takaki Asano, Jonathan Bohlen, Zhiyong Liu, Marcela Moncada-Velez, Yasemin Kendir-Demirkol, Huie Jing, Lucy Bizien, Astrid Marchal, Hassan Abolhassani, Selket Delafontaine, Giorgia Bucciol, Gulsum Ical Bayhan, Sevgi Keles, Ayca Kiykim, Selda Hancerli, Filomeen Haerynck, Benoit Florkin, Nevin Hatipoglu, Tayfun Ozcelik, Guillaume Morelle, Mayana Zatz, Lisa F. P. Ng, David Chien Lye, Barnaby Edward Young, Yee-Sin Leo, Clifton L. Dalgard, Richard P. Lifton, Laurent Renia, Isabelle Meyts, Emmanuelle Jouanguy, Lennart Hammarstrom, Qiang Pan-Hammarstrom, Bertrand Boisson, Paul Bastard, Helen C. Su, Stephanie Boisson-Dupuis, Laurent Abel, Charles M. Rice, Shen-Ying Zhang, Aurelie Cobat, Jean-Laurent Casanova
Summary: In an international cohort of 112 hospitalized children with COVID-19 pneumonia, 12 children with recessive inborn errors of type I interferon immunity were identified. These deficiencies may contribute to the development of COVID-19 pneumonia in children. Additionally, these deficiencies were not found in individuals without pneumonia from SARS-CoV-2 infection.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Axel Rosell, Cecilia Karlstrom, Joakim S. Dahlin, Daryl Boey, Monika Klimkowska, Kajsa Ax, Charlotte Thalin, Johanna Ungerstedt
Summary: There is no evidence of global increase in neutrophil extracellular trap release in patients with systemic mastocytosis.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2024)
