Browsing by Author "Meyts, Isabelle"
Now showing 1 - 5 of 5
Results Per Page
Sort Options
Item Coronavirus disease 2019 in patients with inborn errors of immunity: An international study(2022) Meyts, Isabelle; Bucciol, Giorgia; Quinti, Isabella; Neven, Bénédicte; Fischer, Alain; Seoane, Elena; Lopez-Granados, Eduardo; Gianelli, Carla; Robles-Marhuenda, Angel; Jeandel, Pierre-Yves; Paillard, Catherine; Sankaran, Vijay G.; Demirdag, Yesim Yilmaz; Lougaris, Vassilios; Aiuti, Alessandro; Plebani, Alessandro; Milito, Cinzia; Dalm, Virgil Ash; Guevara-Hoyer, Kissy; Sánchez-Ramón, Silvia; Bezrodnik, Liliana; Barzaghi, Federica; González-Granado, Luis Ignacio; Hayman, Grant R.; Uzel, Gulbu; Mendonça, Leonardo Oliveira; Agostini, Carlo; Spadaro, Giuseppe; Badolato, Raffaele; Soresina, Annarosa; Vermeulen, Francois; Bosteels, Cedric; Lambrecht, Bart N.; Keller, Michael; Mustillo, Peter J.; Abraham, Roshini S.; Gupta, Sudhir; Ozen, Ahmet; Karakoc-Aydiner, Elif; Baris, Safa; Freeman, Alexandra F.; Yamazaki-Nakashimada, Marco; Scheffler-Mendoza, Selma; Espinoza Padilla, Sara; Gennery, Andrew R.; Jolles, Stephen; Espinosa, Yazmin; Poli, Cecilia; Fieschi, Claire; Hauck, Fabian; Cunningham-Rundles, Charlotte; Mahlaouie, Nizar; Sullivan, Kathleen E.; Tangye, Stuart G.; IUIS Committee of Inborn Errors of Immunity;Background: There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. Objective: We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. Methods: An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. Results: We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died. Conclusions: This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.Publication Heterozygous mutations in the C-terminal domain of COPA underlie a complex autoinflammatory syndrome(2024) Delafontaine, Selket; Iannuzzo, Alberto; Bigley, Tarin; Mylemans, Bram; Rana, Ruchit; Baatsen, Pieter; Poli Harlowe, María Cecilia; Rymen, Daisy; Jansen, Katrien; Mekahli, Djalila; Casteels, Ingele; Cassiman, Catherine; Demaerel, Philippe; Lepelley. Alice; Frémond, Marie; Schrijvers, Rik; Bossuyt, Xavier; Vints, Katlijn; Huybrechts, Wim; Tacine, Rachida; Willekens, Karen; Corveleyn, Anniek; Boeckx, Bram; Baggio, Marco; Ehlers, Lisa; Munck, Sebastian; Lambrechts, Diether; Voet, Arnout; Moens, Leen; Bucciol, Giorgia; Cooper, Megan; Davis, Carla; Delon, Jérôme; Meyts, IsabelleMutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular trafficking resulted in a cGAS/STING-dependent upregulation of the type I IFN signaling in patients and patient-derived cell lines, albeit through a distinct molecular mechanism in comparison with mutations in the WD40 domain of COPA. We showed that CTD COPA mutations induce an activation of ER stress and NF-κB signaling in patient-derived primary cell lines. These results demonstrate the importance of the integrity of the CTD of COPA for COPI function and homeostatic intracellular trafficking, essential to ER homeostasis. CTD COPA mutations result in disease by increased ER stress, disturbed intracellular transport, and increased proinflammatory signaling.Publication Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee(2025) Poli Harlowe, María Cecilia; Aksentijevich, Ivona; Aziz, Ahmed; Cunningham, Charlotte; Hambleton, Sophie; Klein, Christoph; Morio, Tomohiro; Picard, Capucine; Puel, Anne; Rezaei, Nima; Seppänen, Mikko; Somech, Raz; Su, Helen; Sullivan, Kathleen; Torgerson, Troy; Meyts, Isabelle; Tangye, StuartThis report provides an updated classification of inborn errors of immunity (IEIs) involving 508 different genes and 17 phenocopies. Of these, we report 67 novel monogenic defects and 2 phenocopies due to neutralizing anti-cytokine autoantibodies or somatic mutations, which either have been discovered since the previous update (published June 2022) or were reported earlier but have been recently confirmed and/or expanded. The new additions were made after rigorous review of new genetic descriptions of IEIs by the International Union of Immunological Societies (IUIS) Expert Committee using criteria established to define IEI. Although similar pathogenic variants in one gene, in terms of both classes of mutation (missense, nonsense, etc.) and impact on protein function, can result in a spectrum of phenotypic manifestations, they are herein classified according to the most consistently reported phenotype. In addition, because different variants in a single gene can result in recognizable diseases due to gain or loss of function, such cases are classified according to their clinical manifestations as a distinct entry in the same or a different table depending on the associated phenotype. This report will serve as a valuable resource for clinical immunologists and geneticists involved in the molecular diagnosis of individuals with heritable and acquired immunological disorders. Moreover, we expect this report to also serve as a valuable resource for all disciplines of medicine, since patients with IEIs may be first seen by rheumatologists, hematologists, allergists, dermatologists, neurologists, gastroenterologists, and pulmonologists, depending upon their spectrum of presenting clinical features. Finally, expanding the known monogenic and related causes of human immune diseases requires dissection of underlying cellular and molecular mechanisms, which reveals fundamental requirements for specific genes, pathways, processes, and even cell types. Such knowledge may not only contribute to improved patient diagnosis and management but also pave the way to the development and implementation of therapies that target the cause-rather than the symptoms-of these conditions.Publication Long-term effects of COVID-19 in patients with primary immunodeficiency: An IPOPI worldwide survey(2025) Van Leeuwen, Leanne; Van Coillie, Samya; Prévot, Johan; Drabwell, Jose; Mahlaoui, Nizar; Sánchez-Ramón, Silvia; Poli Harlowe, María Cecilia; Meyts, Isabelle; Ali, Adli; Lowe, David; Dalm, Virgil; Pergent, MartineBackground: During the coronavirus disease 2019 (COVID-19) pandemic, many individuals developed persistent symptoms after COVID-19. The data on these long-term effects in the primary immunodeficiency (PID) community are limited. Objective: This study aimed to understand long-term symptoms after COVID-19 in patients with PID, focusing on prevalence, risk factors, viral persistence, and the impact of COVID-19 on their health-related quality of life (HR-QoL). Methods: A global, multilingual web-based survey was conducted by the International Patient Organization for Primary Immunodeficiencies between July and October 2023. Self-reported data on demographics, PID diagnosis, comorbidities, COVID-19, and HR-QoL were collected using the EuroQol 5-Dimensions 5-Level (EQ-5D-5L) survey and analyzed. Results: Of the 1160 respondents, 25% reported persistent symptoms after COVID-19. Common symptoms included fatigue, headache, and nasal symptoms. Compared with those respondents without persistent symptoms, those with persistent symptoms after COVID-19 reported a significantly higher prevalence of symptoms across all categories-systemic, pain, cardiopulmonary, gastrointestinal, neurologic, psychological, neurocognitive, and others-except for upper respiratory tract symptoms. Independent risk factors for development of persistent symptoms included female sex, asthma, neurologic diseases, and predominantly antibody deficiency other than common variable immunodeficiency or agammaglobulinemia. In 30% of patients with persistent symptoms, viral clearance was not achieved within 1 month. During the pandemic, HR-QoL declined across all PID categories-even in those without COVID-19, but especially in those with a symptom duration of more than 6 months. Conclusion: Persistent symptoms after COVID-19 are prevalent among patients with PID, with various risk factors identified. The COVID-19 pandemic had a considerable impact on the HR-QoL of patients with PID regardless of COVID-19 status.Publication The 2024 update of IUIS phenotypic classification of human inborn errors of immunity(2025) Aziz, Ahmed; Jeddane, Leïla; Moundir, Abderrahmane; Poli Harlowe, María Cecilia; Aksentijevich, Ivona; Cunningham, Charlotte; Hambleton, Sophie; Klein, Christoph; Morio, Tomohiro; Picard, Capucine; Puel, Anne; Rezaei, Nima; Seppänen, Mikko; Somech, Raz; Su, Helen; Sullivan, Kathleen; Torgerson, Troy; Tangye, Stuart; Meyts, IsabelleHere, we report the 2024 update of the phenotypic classification by the International Union of Immunological Societies (IUIS) expert committee (EC) on inborn errors of immunity (IEI), which accompanies and complements the 2024 genotypic classification. The aim of this classification is to help diagnosis for clinicians at the bedside and focuses on clinical features and basic laboratory phenotypes of specific IEI. In this update, 559 IEI are described, including 67 novel monogenic defects and 2 new phenocopies. This phenotypic classification is presented in the form of decision trees when possible, with essential clinical or immunological phenotype entries.