Article
Mathematics, Interdisciplinary Applications
Vedrana Makevic, Ivan D. Milovanovich, Nevena Popovac, Radmila Jankovic, Jelena Trajkovic, Andrija Vukovic, Bojana Milosevic, Jovan Jevtic, Silvio R. de Luka, Andjelija Z. Ilic
Summary: This study aimed to differentiate between the two clinical phenotypes of inflammatory bowel disease (IBD) in pediatric patients, or either of the phenotypes versus control, using the fractal dimension and lacunarity of intestinal cell chromatin. The results showed significant differences in fractal dimension and lacunarity between the ulcerative colits (UC) group and Crohn's disease (CD) group, as well as the UC group and control group in most colon segments. The fractal dimension was also able to differentiate CD from the control group in the ileocecal valve and rectum. This study identified the potential of fractal analysis of intestinal cell nuclei as an observer-independent histological tool for diagnosing ulcerative colitis, paving the way for the development of computer-aided diagnosis systems.
FRACTAL AND FRACTIONAL
(2023)
Review
Immunology
Yoji Sasahara, Takashi Uchida, Tasuku Suzuki, Daiki Abukawa
Summary: This review investigates the prevalence, clinical manifestation, genetic profile, and treatment of patients with early-onset inflammatory bowel disease (IBD) in Southeast and East Asia, specifically looking at the association with primary immunodeficiency diseases (PIDs). The study found that the prevalence of PID associated with IBD was higher in Southeast and East Asia compared to Western countries, and patients with bloody stools as an early symptom were more likely to have monogenic diseases. Comprehensive molecular diagnosis has been widely applied in this region to screen for PID-associated IBD patients. These findings contribute to the understanding of monogenic PIDs in early-onset IBD patients and their clinical manifestations and genetic profiles compared to Western countries.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Sylwia Fabiszewska, Edyta Derda, Edyta Szymanska, Marcin Osiecki, Jaroslaw Kierkus
Summary: This study retrospectively analyzed 16 children with VEO-IBD who received vedolizumab, showing that 56.3% of patients had a clinical response at the 4th dose week with improvements in nutritional status. There were no reported infusion reactions or serious adverse events/infections.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Anne. E. E. Levine, Dominique Mark, Laila Smith, Hengqi. B. B. Zheng, David. L. L. Suskind
Summary: Inflammatory bowel disease (IBD) is a condition treated with various immunomodulating and immunosuppressive therapies, but targeted treatments for specific disease phenotypes are lacking. However, monogenic IBD with identifiable genetic defects offers the potential for precision therapeutics. The advent of genetic sequencing platforms has led to an increased identification of monogenic immunodeficiencies that cause IBD, particularly a subpopulation called very early onset inflammatory bowel disease (VEO-IBD) with an onset age of less than six years old. This review discusses the current state of disease-specific targeted therapies and empiric treatment for undifferentiated causes of VEO-IBD.
Article
Immunology
Eliana Shaul, Maire A. Conrad, Noor Dawany, Trusha Patel, Megan C. Canavan, Alyssa Baccarella, Sarah Weinbrom, Daniel Aleynick, Kathleen E. Sullivan, Judith R. Kelsen
Summary: This study evaluated the clinical response to canakinumab in children with refractory very early onset inflammatory bowel disease (VEO-IBD). The results suggest that canakinumab may be an effective and safe treatment for VEO-IBD patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pediatrics
Laurence Chapuy, Bertrand Leduc, David Godin, Amelie Damphousse, Nathalie Patey, Dorothee Dal Soglio, Prevost Jantchou, Colette Deslandres
Summary: This study reports the phenotype and outcomes of very-early-onset inflammatory bowel disease (VEO-IBD) and early-onset IBD (EO-IBD) in a Montreal pediatric cohort. The results showed differences in phenotype between VEO-IBD and EO-IBD, but there was no significant difference in the rate of steroid-free clinical remission between the two groups at 1-year post-diagnosis and at the end of follow-up.
FRONTIERS IN PEDIATRICS
(2023)
Review
Gastroenterology & Hepatology
M. Ellen Kuenzig, Stephen G. Fung, Luba Marderfeld, Joyce W. Y. Mak, Gilaad G. Kaplan, Siew C. Ng, David C. Wilson, Fiona Cameron, Paul Henderson, Paulo G. Kotze, Jasmine Bhatti, Vixey Fang, Samantha Gerber, Evelyne Guay, Supun Kotteduwa Jayawarden, Leo Kadota, Fernando D. Maldonado, Jessica Amankwah Osei, Ryan Sandarage, Amanda Stanton, Melissa Wan, Eric Benchimol
Summary: The incidence of pediatric-onset inflammatory bowel disease (IBD) is increasing worldwide, with the highest rates in Northern Europe and North America and the lowest rates in Southern Europe, Asia, and the Middle East. Most studies reported significant increases in incidence, while there is limited data on very early onset IBD.
Article
Gastroenterology & Hepatology
Mania Ackermann, Adele Mucci, Amanda McCabe, Sandy Frei, Kayla Wright, Scott B. Snapper, Nico Lachmann, David A. Williams, Christian Brendel
Summary: Mutations in IL10 or the IL10 receptor lead to VEO-IBD, and gene therapy as well as macrophage transplantation have been investigated in a mouse model, showing potential for ameliorating colitis symptoms.
JOURNAL OF CROHNS & COLITIS
(2021)
Article
Immunology
Judith Kelsen, Noor Dawany, Maire Conrad, Trusha Patel, Marcella Devoto, Kelly Maurer, Kathleen E. Sullivan
Summary: The genetic causes of very early onset inflammatory bowel disease are diverse, ranging from pure epithelial defects to classic T cell defects. Genetic testing is currently the most reliable method for identifying monogenic cases of very early onset IBD.
CLINICAL IMMUNOLOGY
(2022)
Editorial Material
Gastroenterology & Hepatology
Jodie Ouahed
Summary: Research has identified over 70 genes associated with very early onset inflammatory bowel disease (VEOIBD), with some mutations leading to the disease. This provides valuable insights for the treatment of patients with VEOIBD.
INFLAMMATORY BOWEL DISEASES
(2021)
Review
Pediatrics
Marleen Bouhuys, Willem S. Lexmond, Patrick F. van Rheenen
Summary: Inflammatory bowel diseases (IBDs) are chronic, immune-mediated disorders that include Crohn's disease and ulcerative colitis. Pediatric onset of the disease occurs in about 10% of cases. The management of pediatric IBD has evolved, with anti-tumor necrosis factor therapy being used upfront for patients at high risk for complications. Biochemical or endoscopic remission is the therapeutic goal, and pediatric IBD comes with unique challenges such as growth impairment and psychological issues. General pediatricians play a crucial role in integrating these challenges in the clinical care of patients with IBD and optimizing their outcomes.
Article
Gastroenterology & Hepatology
Takahiro Kudo, Katsuhiro Arai, Keiichi Uchida, Hitoshi Tajiri, Ryota Hokari, Yasuo Suzuki, Toshiaki Shimizu
Summary: Very early-onset inflammatory bowel disease, diagnosed before 6 years of age, presents various challenges due to differential diagnoses, including primary immunodeficiency disorders. Approximately 40 patients are diagnosed with this condition yearly in Japan, and imaging studies, particularly for small bowel lesions, can be difficult. However, a comprehensive approach involving immunological and genetic analyses appears to be useful for diagnosing immunodeficiency-associated inflammatory bowel disease.
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Immunology
Reiko Kyodo, Ichiro Takeuchi, Satoshi Narumi, Hirotaka Shimizu, Kenichiro Hata, Takako Yoshioka, Kanako Tanase-Nakao, Toshiaki Shimizu, Katsuhiro Arai
Summary: This study reported a case of a 1-year-old boy diagnosed with very early-onset inflammatory bowel disease (VEO-IBD) and identified genetic variants affecting dual oxidase 2 (DUOX2) function as potential molecular risk factors for VEO-IBD.
CLINICAL IMMUNOLOGY
(2022)
Review
Immunology
Hengqi B. Zheng, M. Teresa de la Morena, David L. Suskind
Summary: VEO-IBD represents a group of patients diagnosed with IBD before the age of 6, which can be associated with monogenic variations in over 70 genes involved in multiple immune pathways. Although monogenic defects are rare in VEO-IBD, diagnosis of these variants often dictates specific treatment methods.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pediatrics
So Yoon Choi, Ben Kang
Summary: The introduction of biological agents, particularly anti-TNF agents, has significantly improved the long-term prognosis of patients with inflammatory bowel disease (IBD). In pediatric populations, only two biological agents, infliximab (IFX) and adalimumab (ADL), have been approved for use. ADL has shown efficacy in achieving mucosal healing (MH) and histological remission in both naive patients and those who have previously received biologic treatment. Therapeutic drug monitoring may further enhance the effectiveness of ADL treatment and reduce treatment failure.
FRONTIERS IN PEDIATRICS
(2022)
Article
Gastroenterology & Hepatology
Sascha Cording, Ludovic Lhermitte, Georgia Malamut, Sofia Berrabah, Amelie Trinquand, Nicolas Guegan, Patrick Villarese, Sophie Kaltenbach, Bertrand Meresse, Sherine Khater, Michael Dussiot, Marc Bras, Morgane Cheminant, Bruno Tesson, Christine Bole-Feysot, Julie Bruneau, Thierry Jo Molina, David Sibon, Elizabeth Macintyre, Olivier Hermine, Christophe Cellier, Vahid Asnafi, Nadine Cerf-Bensussan
Summary: The study identified mutations activating the JAK1-STAT3 pathway as the main drivers of enteropathy-associated T-cell lymphoma, potentially in combination with mutations in negative regulators of NF-kappa B. These mutations could promote the clonal emergence of malignant lymphocytes in the cytokine-rich coeliac intestine, and are attractive therapeutic targets for treating refractory celiac disease and blocking progression towards EATL.
Article
Rheumatology
Jerome Hadjadj, Delphine Planas, Amani Ouedrani, Solene Buffier, Laure Delage, Yann Nguyen, Timothee Bruel, Marie-Claude Stolzenberg, Isabelle Staropoli, Natalia Ermak, Laure Macraigne, Caroline Morbieu, Soledad Henriquez, David Veyer, Helene Pere, Marion Casadevall, Luc Mouthon, Frederic Rieux-Laucat, Lucienne Chatenoud, Olivier Schwartz, Benjamin Terrier
Summary: This study evaluated the immune responses in immunocompromised patients with systemic inflammatory diseases after receiving BNT162b2 vaccine, finding that rituximab and methotrexate had different impacts on the vaccine's immunogenicity, with the Delta variant fully escaping the humoral response in individuals treated with rituximab. Efforts to improve the immunogenicity of BNT162b2 in immunocompromised individuals are supported by these findings.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Hematology
C. Dhunputh, S. Ducassou, H. Fernandes, Capucine Picard, Frederic Rieux-Laucat, J. -F. Viallard, E. Lazaro, O. Hermine, M. Jouvray, I. Machelard, A. Lambilliotte, M. Malphettes, D. Moshous, B. Neven, A. Gauthier, N. Garnier, T. Leblanc, J. Landman-Parker, G. Leverger, N. Aladjidi
Article
Allergy
Jeremy Boussier, Nader Yatim, Armance Marchal, Jerome Hadjadj, Bruno Charbit, Carine El Sissy, Nicolas Carlier, Frederic Pene, Luc Mouthon, Pierre-Louis Tharaux, Anne Bergeron, David M. Smadja, Frederic Rieux-Laucat, Darragh Duffy, Solen Kerneis, Veronique Fremeaux-Bacchi, Benjamin Terrier
Summary: This study elucidates the role of the alternative pathway in severe COVID-19 and provides additional rationale for the testing of drugs inhibiting the alternative pathway of the complement system.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Pediatrics
Clara Cebron, Astrid Godron-Dubrasquet, Nathalie Aladjidi, Gwenaelle Roussey, Olivia Boyer, Marina Avramescu, Veronique Baudouin, Joelle Terzic, Emma Allain-Launay, Frederic Rieux-Laucat, Stephane Decramer, Thomas Simon, Jerome Harambat
Summary: This study suggests a possible association between nephrotic syndrome (NS) and lymphoproliferative syndrome. The findings indicate that malignant or benign cell proliferation can occur in children with idiopathic NS within a few years. Viral infections may contribute to this association.
PEDIATRIC NEPHROLOGY
(2022)
Article
Hematology
Tala Shahin, Daniel Mayr, Mohamed R. Shoeb, Hye Sun Kuehn, Birgit Hoeger, Sarah Giuliani, Lisa M. Gawriyski, Ozlem Yuce Petronczki, Jerome Hadjadj, Sevgi Kostel Bal, Samaneh Zoghi, Matthias Haimel, Raul Jimenez Heredia, David Boutboul, Michael P. Triebwasser, Fanny Rialland-Battisti, Nathalie Costedoat Chalumeau, Pierre Quartier, Stuart G. Tangye, Thomas A. Fleisher, Nima Rezaei, Neil Romberg, Sylvain Latour, Markku Varjosalo, Florian Halbritter, Frederic Rieux-Laucat, Irinka Castanon, Sergio D. Rosenzweig, Kaan Boztug
Summary: Germline mutations in IKZF2 have been found in patients with systemic lupus erythematosus, immune thrombocytopenia, or EBV-associated hemophagocytic lymphohistiocytosis. These mutations affect the function of Helios protein and lead to abnormalities in both the immune and hematopoietic systems. The study highlights the importance of Helios in human immunity and hematopoiesis.
Article
Immunology
Akihiro Hoshino, David Boutboul, Yuan Zhang, Hye Sun Kuehn, Jerome Hadjadj, Nihal Ozdemir, Tiraje Celkan, Christoph Walz, Capucine Picard, Christelle Lenoir, Nizar Mahlaoui, Christoph Klein, Xiao Peng, Antoine Azar, Erin Reigh, Morgane Cheminant, Alain Fischer, Frederic Rieux-Laucat, Isabelle Callebaut, Fabian Hauck, Joshua Milner, Sergio D. Rosenzweig, Sylvain Latour
Summary: This study identified IKZF1 variants in the DNA binding domain that cause inflammatory, autoimmune, allergic symptoms, and abnormal plasma cell proliferation. These variants act as gain-of-function alleles, leading to increased gene expression associated with T(H)2 and plasma cell differentiation. Treatment with Lenalidomide can correct these abnormalities.
SCIENCE IMMUNOLOGY
(2022)
Editorial Material
Gastroenterology & Hepatology
Fabienne Charbit-Henrion, Manon Haas, Stanislas Chaussade, Christophe Cellier, Nadine Cerf-Bensussan, Georgia Malamut
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Immunology
Vincent Allain, Virginie Grandin, Veronique Meignin, Remi Bertinchamp, David Boutboul, Claire Fieschi, Lionel Galicier, Laurence Gerard, Marion Malphettes, Jacinta Bustamante, Mathieu Fusaro, Nathalie Lambert, Jeremie Rosain, Christelle Lenoir, Sven Kracker, Frederic Rieux-Laucat, Sylvain Latour, Jean-Pierre De Villartay, Capucine Picard, Eric Oksenhendler
Summary: This study found that lymphoma may be a revealing symptom of an underlying primary immunodeficiency in patients with hypogammaglobulinemia, challenging the distinction between primary and secondary hypogammaglobulinemia. The occurrence of Hodgkin lymphoma was more common prior to the diagnosis of hypogammaglobulinemia, while MALT lymphoma was absent. Genetic analysis identified a molecular diagnosis in some patients, with a significant portion presenting with late-onset combined immunodeficiency.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Cell Biology
Steicy Sobrino, Alessandra Magnani, Michaela Semeraro, Loredana Martignetti, Akira Cortal, Adeline Denis, Chloe Couzin, Capucine Picard, Jacinta Bustamante, Elisa Magrin, Laure Joseph, Cecile Roudaut, Aurelie Gabrion, Tayebeh Soheili, Corinne Cordier, Olivier Lortholary, Francois Lefrere, Frederic Rieux-Laucat, Jean-Laurent Casanova, Sylvain Bodard, Nathalie Boddaert, Adrian J. Thrasher, Fabien Touzot, Sophie Taque, Felipe Suarez, Ambroise Marcais, Agathe Guilloux, Chantal Lagresle-Peyrou, Anne Galy, Antonio Rausell, Stephane Blanche, Marina Cavazzana, Emmanuelle Six
Summary: X-linked chronic granulomatous disease (CGD) is a serious condition associated with defective phagocytosis, infections, and inflammatory complications. A clinical trial of lentivirus-based gene therapy was conducted on four patients, showing successful engraftment and clinical benefits in two patients, while the other two experienced loss of gene-corrected cells. Single-cell transcriptomic analysis revealed lower levels of hematopoietic stem cells (HSCs) in CGD patients, especially in those with poor engraftment. Aberrant HSC state and elevated interferon genes were identified as predictors of HSC engraftment failure.
CELL REPORTS MEDICINE
(2023)
Article
Immunology
Marco M. M. Rodari, Dominique Cazals-Hatem, Mathieu Uzzan, Nicolas Martin Silva, Anis Khiat, Minh Chau Ta, Ludovic Lhermitte, Aurore Touzart, Sylvain Hanein, Clea Rouillon, Francisca Joly, Adrienne Elmorjani, Julie Steffann, Nadine Cerf-Bensussan, Marianna Parlato, Fabienne Charbit-Henrion
Summary: This study demonstrates that impaired regulation of SOCS1 can lead to a wide range of intestinal manifestations, emphasizing the need for genetic screening and considering the use of JAK inhibitors in severe treatment-refractory enteropathies.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Cell & Tissue Engineering
Celine Banal, Eddy Quelennec, Cecile Talbotec, Anis Khiat, Fabienne Charbit-Henrion, Nadine Cerf-Bensussan, Nathalie Lefort, Corinne Lebreton
Summary: Mutations in UNC45A can cause a syndrome with symptoms including cholestasis, diarrhea, hearing loss, and bone fragility. We created iPSCs from a patient with a homozygous missense mutation in UNC45A using integration-free Sendal virus, and these cells showed normal karyotype, expressed pluripotency markers, and were able to differentiate into the three germ cell layers.
STEM CELL RESEARCH
(2023)
Article
Gastroenterology & Hepatology
Annick Hamon, Dominique Cazals-Hatem, Carmen Stefanescu, Mathieu Uzzan, Xavier Treton, Alain Sauvanet, Yves Panis, Marie Monsinjon, Fanny Bonvalet, Olivier Corcos, Emilie Azouguene, Nadine Cerf-Bensussan, Yoram Bouhnik, Fabienne Charbit-Henrion
Summary: This article reports the case of two French female siblings with CEAS related to SLCO2A1 mutations. Next-generation sequencing identified two compound heterozygous variants in the SLCO2A1 gene in one sister, which were also present in the other sister. This study suggests that CEAS may not be exclusive to Asian populations and should be considered in European patients with intractable recurrent ulcerations of the small intestine mimicking Crohn's disease.
JOURNAL OF CROHNS & COLITIS
(2023)
Article
Medicine, Research & Experimental
Remi Duclaux-Loras, Corinne Lebreton, Jeremy Berthelet, Fabienne Charbit-Henrion, Ophelie Nicolle, Celine Revenu de Courtils, Stephanie Waich, Taras Valovka, Anis Khiat, Marion Rabant, Caroline Racine, Ida Chiara Guerrera, Julia Baptista, Maxime M. Mahe, Michael W. Hess, Beatrice Durel, Nathalie Lefort, Celine Banal, Melanie Parisot, Cecile Talbotec, Florence Lacaille, Emmanuelle Ecochard-Dugelay, Arzu Meltem Demir, Georg F. Vogel, Laurence Faivre, Astor Rodrigues, Darren Fowler, Andreas R. Janecke, Thomas Mueller, Lukas A. Huber, Fernando Rodrigues-Lima, Frank M. Ruemmele, Holm H. Uhlig, Filippo Del Bene, Gregoire Michaux, Nadine Cerf-Bensussan, Marianna Parlato
Summary: Variants in the UNC45A cochaperone can cause a syndrome with symptoms including diarrhea, cholestasis, deafness, and bone fragility. This study provides evidence that UNC45A plays a crucial role in epithelial morphogenesis and its loss can lead to a variant of microvillus inclusion disease.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Meeting Abstract
Immunology
Daniel Mayr, Tala Shahin, Mohamed Shoeb, Hyesun Kuehn, Birgit Hoger, Sarah Giuliani, Lisa Gawriyski, Ozlem Yuece Petronczki, Jerome Hadjadj, Sevgi Kostel Bal, Samaneh Zoghi, Matthias Haimel, Raul Jimenez Heredia, David Boutboul, Michael Triebwasser, Fanny Rialland-Battisti, Nathalie Costedoat Chalumeau, Pierre Quartier, Stuart Tangye, Thomas Fleisher, Nima Rezaei, Neil Romberg, Sylvain Latour, Markku Varjosalo, Florian Halbritter, Frederic Rieux-Laucat, Irinka Castanon, Sergio Rosenzweig, Kaan Boztug
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
