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1. Elevated monocyte HLA-DR in pediatric secondary hemophagocytic lymphohistiocytosis: a retrospective study

Author

Sylvain Raimbault, Guillaume Monneret, Morgane Gossez, Fabienne Venet, Alexandre Belot, Franck Zekre, Solene Remy, and Etienne Javouhey

Subjects
hemophagocytic lymphohistiocytosis, monocyte HLA-DR, macrophage activation syndrome, lymphocyte activation, cytokine storm, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionHemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition, and its diagnosis may be challenging. In particular, some cases show close similarities to sepsis (fever, organ failure, and high ferritin), but their treatment, while urgent, differ: prompt broad-spectrum antibiotherapy for sepsis and immunosuppressive treatment for HLH. We questioned whether monocyte human leucocyte antigen (mHLA)–DR could be a diagnostic marker for secondary HLH (sHLH).MethodsWe retrospectively reviewed data from patients with a sHLH diagnosis and mHLA-DR quantification. mHLA-DR data from healthy children and children with septic shock, whose HLA-DR expression is reduced, from a previously published study were also included for comparison.ResultsSix patients with sHLH had mHLA-DR quantification. The median level of monocyte mHLA-DR expression in patients with sHLH [79,409 antibodies bound per cell (AB/C), interquartile range (IQR) (75,734–86,453)] was significantly higher than that in healthy children and those with septic shock (29,668 AB/C, IQR (24,335–39,199), and 7,493 AB/C, IQR (3,758–14,659), respectively). Each patient with sHLH had a mHLA-DR higher than our laboratory normal values. Four patients had a second mHLA-DR sampling 2 to 4 days after the initial analysis and treatment initiation with high-dose corticosteroids; for all patients, mHLA-DR decreased to within or close to the normal range. One patient with systemic juvenile idiopathic arthritis had repeated mHLA-DR measurements over a 200-day period during which she underwent four HLH episodes. mHLA-DR increased during relapses and normalized after treatment incrementation.ConclusionIn this small series, mHLA-DR was systematically elevated in patients with sHLH. Elevated mHLA-DR could contribute to sHLH diagnosis and help earlier distinction with septic shock.

Published
2023
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2. H syndrome treated with Tocilizumab: two case reports and literature review

Author

Robin Jacquot, Maurine Jouret, Mathieu Gerfaud Valentin, Maël Richard, Yvan Jamilloux, Florent Rousset, Jean-François Emile, Julien Haroche, Lars Steinmüller, Franck Zekre, Alice Phan, Alexandre Belot, and Pascal Seve

Subjects
H syndrome, SLC29A3, tocilizumab, monogenic autoinflammatory disease, hyperpigmentation, recurrent febrile attacks, Immunologic diseases. Allergy, RC581-607
Abstract

H syndrome is a rare autosomal recessive genetic disorder characterized by the following clinical features: cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, short stature, hallux valgus, hyperglycemia, fixed flexion contractures of the toe joints, and the proximal interphalangeal joints. In rare cases, autoinflammatory and lymphoproliferative manifestations have also been reported. This disorder is due to loss-of-function mutations in SLC29A3 gene, which encode the equilibrative nucleoside transporter ENT3. This deficiency leads to abnormal function and proliferation of histiocytes. H syndrome is part of the R-group of histiocytosis. We report two different cases, one was diagnosed in adulthood and the other in childhood. The first case reported is a 37-year-old woman suffering from H syndrome with an autoinflammatory systemic disease that begins in adulthood (fever and diffuse organ’s infiltration) and with cutaneous, articular, auditory, and endocrinological manifestations since childhood. The second case reported is a 2-year-old girl with autoinflammatory, endocrine, and cutaneous symptoms (fever, lymphadenopathy, organomegaly, growth delay, and cutaneous hyperpigmentation). Homozygous mutations in SLC29A3 confirmed the diagnosis of H syndrome in both cases. Each patient was treated with Tocilizumab with a significant improvement for lymphoproliferative, autoinflammatory, and cutaneous manifestations. Both cases were reported to show the multiple characteristics of this rare syndrome, which can be diagnosed either in childhood or in adulthood. In addition, an overview of the literature suggested Tocilizumab efficiency.

Published
2023
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3. Rescue of Pap-Mas in Systemic JIA Using Janus Kinase Inhibitors, Case Report and Systematic Review

Author

Franck Zekre, Anita Duncan, Audrey Laurent, Maud Tusseau, Rémi Pescarmona, Sophie Collardeau-Frachon, Camille Ohlmann, Sébastien Viel, Philippe Reix, Sarah Benezech, and Alexandre Belot

Subjects
systemic-juvenile idiopathic arthritis, pulmonary alveolar proteinosis, macrophage activation syndrome, Janus Kinase inhibitors, IL-18, Medicine
Abstract

Introduction: Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as potential risk factors. We report on a new case with longitudinal immunomonitoring successfully treated by Janus Kinase inhibitors (JAKi) and review past clinical descriptions of this new entity. Methods: We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment. Results: Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-γ or IL-1β/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis. Conclusions: JAKi represent a promising option in the treatment of lung disease associated with sJIA.

Published
2023
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4. Increased Immunity against the Oral Germs Porphyromonas gingivalis and Prevotella intermedia in Different Categories of Juvenile Idiopathic Arthritis

Author

Franck Zekre, Rolando Cimaz, Mireille Paul, Teresa Giani, Louis Waeckel, Anne-Emmanuelle Berger, Jean-Louis Stephan, Myriam Normand, Stéphane Paul, and Hubert Marotte

Subjects
juvenile idiopathic arthritis, oligoarthritis, enthesis related arthritis, anti-Porphyromonas gingivalis antibody, anti-Prevotella intermedia antibody, Biology (General), QH301-705.5
Abstract

(1) Background: The link between periodontal disease and rheumatoid arthritis (RA) is now widely reported. Several studies suggest the role of Porphyromonas gingivalis (P. gingivalis) in the pathophysiology of RA and some observations highlight the improvement of the disease activity induced by therapies against P. gingivalis. We have very little data on the prevalence of P. gingivalis carriage in patients with juvenile idiopathic arthritis (JIA) and its possible involvement in the pathophysiology of inflammatory joint diseases in children. (2) Methods: The specific IgG responses against P. gingivalis and Prevotella intermedia (P. intermedia) were determined in a cohort of 101 patients with JIA and 19 patients with other autoimmune diseases (inflammatory bowel disease and type 1 diabetes). (3) Results: Specific anti-P. gingivalis and anti-P. intermedia IgG titers were higher in JIA group than in control groups. These differences were mainly observed in the oligoarthritis group. The same pattern was observed in enthesitis-related arthritis (ERA). (4) Conclusions: Children with oligoarticular and ERA subsets had higher IgG titers to P. gingivalis and P. intermedia. These results suggest involvement of an oral dysbiosis in the occurrence of JIA in these subgroups.

Published
2022
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5. Hyper inflammatory syndrome following COVID-19 mRNA vaccine in children: A national post-authorization pharmacovigilance study

Author

Naïm Ouldali, Haleh Bagheri, Francesco Salvo, Denise Antona, Antoine Pariente, Claire Leblanc, Martine Tebacher, Joëlle Micallef, Corinne Levy, Robert Cohen, Etienne Javouhey, Brigitte Bader-Meunier, Caroline Ovaert, Sylvain Renolleau, Veronique Hentgen, Isabelle Kone-Paut, Nina Deschamps, Loïc De Pontual, Xavier Iriart, Christelle Gras-Le Guen, François Angoulvant, Alexandre Belot, Aurelie Donzeau, Layal El Aridi, Sophie Lety, Bertrand Leboucher, Agnes Baur, Lucas Jeusset, Maelle Selegny, Cristian Fedorczuk, Marion Lajus, Philippe Bensaid, Yacine Laoudi, Charlotte Pons, Anne-Cécile Robert, Camille Beaucourt, Muriel Richard, Etienne Goisque, Olivier Brissaud, Pierre Segretin, Julie Molimard, Marie-Clothilde Orecel, Gregoire Benoit, Lucille Bongiovanni, Margaux Guerder, Robin Pouyau, Jean-Marie De Guillebon De Resnes, Ellia Mezgueldi, Fleur Cour-Andlauer, Come Horvat, Pierre Poinsot, Cecile Frachette, Antoine Ouziel, Yves Gillet, Catherine Barrey, Jacques Brouard, Florence Villedieu, Vathanaksambath Ro, Narcisse Elanga, Vincent Gajdos, Romain Basmaci, Hadile Mutar, Sébastien Rouget, Elodie Nattes, Isabelle Hau, Sandra Biscardi, Houmam El Jurdi, Camille Jung, Denis Semama, Frederic Huet, Anne-Marie Zoccarato, Mayssa Sarakbi, Guillaume Mortamet, Cécile Bost-Bru, Joachim Bassil, Caroline Vinit, Véronique Hentgen, Pascal Leroux, Valérie Bertrand, Caroline Parrod, Irina Craiu, Philippe Durand, Pierre Tissiere, Caroline Claude, Guillaume Morelle, Tamazoust Guiddir, Charlotte Borocco, Frédérique Delion, Camille Guillot, Stéphane Leteurtre, François Dubos, Mylene Jouancastay, Alain Martinot, Valentine Voeusler, Jeanne Languepin, Nathalie Garrec, Arnaud Chalvon Demersay, Aurélie Morand, Emmanuelle Bosdure, Noémie Vanel, Fabrice Ughetto, Fabrice Michel, Marie Caujolle, Renaud Blonde, Jacqueline Nguyen, Olivier Vignaud, Caroline Masserot-Lureau, François Gouraud, Carine Araujo, Tara Ingrao, Sanaa Naji, Mohammed Sehaba, Christine Roche, Aurelia Carbasse, Christophe Milesi, Mustapha Mazeghrane, Sandrine Haupt, Cyril Schweitzer, Benedicte Romefort, Elise Launay, Christèle Gras-Le Guen, Ahmed Ali, Nathalie Blot, Antoine Tran, Anne Rancurel, Mickael Afanetti, Sophie Odorico, Deborah Talmud, Anais Chosidow, Anne-Sophie Romain, Emmanuel Grimprel, Marie Pouletty, Jean Gaschignard, Olivier Corseri, Albert Faye, Isabelle Melki, Camille Ducrocq, Cherine Benzoïd, Johanna Lokmer, Stéphane Dauger, Maryline Chomton, Anna Deho, Fleur Lebourgeois, Fabrice Lesage, Florence Moulin, Laurent Dupic, Yael Pinhas, Agathe Debray, Martin Chalumeau, Véronique Abadie, Pierre Frange, Jeremie F Cohen, Slimane Allali, William Curtis, Zahra Belhadjer, Johanne Auriau, Mathilde Méot, Lucile Houyel, Damien Bonnet, Christophe Delacourt, Brigitte Bader Meunier, Pierre Quartier, Youssef Shaim, Laurence Baril, Samuel Crommelynck, Baptiste Jacquot, Philippe Blanc, Natacha Maledon, Blandine Robert, Camille Loeile, Clémence Cazau, Gauthier Loron, Simona Gaga, Cécile Vittot, Loubna El Nabhani, François Buisson, Muriel Prudent, Hugues Flodrops, Fadhila Mokraoui, Simon Escoda, Laurent Bonnemains, Sarah-Louisa Mahi, Clara Mertes, Joelle Terzic, Julie Helms, Charlotte Idier, Soraya Chenichene, Nicoleta Magdolena Ursulescu, Gladys Beaujour, Abdelhak Hakim, Alice Miquel, Agnès Rey, Arnaud Wiedermann, Anne Charbonneau, Agnès Veauvy-Juven, Alexandrine Ferry, Alexis Mandelcwajg, Alix Rousseau, Amandine Prenant, Anne-Laure Bourneuf, Anne Filleron, Audrey Robine, Arthur Félix, Aude Parizel, Aurélie Labarre, Aymeric Cantais, Barbara Ros, Basile Coulon, Blandine Biot, Bérengère Dalichoux, Benjamin Fournier, Benoit Cagnard, Blandine Vanel, David Brossier, Bruno Ménager, Bruno Ozanne, Carole Marie-Jeanne, Camille Bergerot, Camille Chavy, Camille Guidon, Candice Fabre, Caroline Galeotti, Catherine Baker, Claire Ballot-Schmit, Céline Belleau, Céline Charasse, Caroline Favel, Chadia Toumi, Charlène Ferrandiz, Charlotte Couturier, Charlotte Pouchoux, Maryline Chomton-Cailliez, Charlotte Kevorkian-Verguet, Clément Brunet, Céline Manteau, Clémence Mougey, Coline Santy, Coralie Fitament, Charlotte Petriat, Charlotte Rebelle, Cyril Charron, Maxime Dartus, David Toulorge, Cécile Guillou-Debuisson, Dorann Bartebin, Valérie Klein, E Broustal, E Desselas, Elodie Marteau, Emmanuelle Bouvrot, Elise Delacroix, Edeline Coinde, Loubna Elnabhani, Elsa Amouyal, Emilie Chaillou, Emeline Gabilly-Bernard, Emilie Ruiz, Emilie Thibault, Emilie Robin, Etienne Darrieux, Eva Blondel, Floriane Socchi, François Cazassus, Fanny Bajolle, Fatma Lacin, Fouad Madhi, Franck Zekre, François Guerin, Gerald Boussicault, Henri Ginies, Gnansounou Magloire, Guilhem Arnold, Ines Coulognon, Iona Sicard-Cras, Jean-Emmanuel Kahn, Jeanne Bordet, Jeanne-Lise Fausser, Jean-François Baleine, Josephine Brice, Julie Gendras, Kaan Pekin, Karine Norbert, Clément Karsenty, Léa Savary, Laurence Martinat, Léa Lesniewski, Lorelei Charbonnier, Louise Alexandre, Lucas Percheron, Marie Vincenti, Manon Lanzini, Margot Grisval, Marianne Mercy, Marie-Emilie Lampin, Marie Desgranges, Marie Duperril, Marie-Clothilde Orcel, Marion Audier, Marion Favier, Mathieu Carpentier, Mathilde Balcean, Mathilde Bonnet, Maurine Jouret, Marie Delattre, Michael Levy, Michael Valensi, Mickael Shum, Morgane Dumortier, Morgane Gelin, Morgane Nemmouchi, Morgane Williaume, M Sebaha, Nicoleta Genetay-Stanescu, Nathan Giroux, Nicolas Crassard, Neil Derridj, Noemie Lachaume, Oscar Werner, Olivier Guilluy, Olivier Richer, Olivier Tirel, Aurianne Pauvert, Paul Casha, Noémie Perez, Pauline Gras, Pierre-Louis Leger, Marion Pinchou, Pierre Mornand, Prisca Largo, Ramona-Christina Ibanez, Charlotte Roulland, Salam Hadah Albarazi, Said Bichali, Sarah Faton, Amandine Schott, Sébastien Walser, Severine Guillaume, Solene Vincent, Sophie Galene-Gromez, Stanislas Kozisek, Thierry Maugard, Thierry Blanc, Thierry Navarro, Thomas Lauvray, Tamas Kovacs, Valérie Launay, Véronique Despert, Victoria Lhostis, Virginie Gall, Xavier Micaelli, Yasmine Benadjaoud, Zied Matoussi, Hélène Géniaux, Anthony Facile, Tessa Pietri, Pascale Palassin, Sylvine Pinel, Laurent Chouchana, Delphine Callot, Charlène Boulay, Hôpital Robert Debré, CHU Sainte Justine [Montréal], Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, CHU Marseille, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHI Créteil, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [CHU Necker] (RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier de Versailles André Mignot (CHV), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Hôpital Bicêtre, Université Paris-Saclay, CH de Saint-Malo [Broussais], Hôpital Jean Verdier [AP-HP], Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), European Society for Paediatric Infectious Diseases, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [Paris] (Institut IMAGINE/RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Imagine [Paris Necker] (2I), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE)

Subjects
Oncology, [SDV]Life Sciences [q-bio], Health Policy, Multisystem inflammatory syndrome in children, Internal Medicine, COVID-19 mRNA vaccine, BNT162b2, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SARS-COV-2, Hyper-inflammatory syndrome, Child
Abstract

International audience; BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is the most severe clinical entity associated with pediatric SARS-CoV-2 infection with a putative role of the spike protein into the immune system activation. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. We aimed to assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children. METHODS: We conducted a post-authorization national population-based surveillance using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines. All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12-17-year-old children between June 15(th), 2021 and January 1(st), 2022, were reported. Cases were reviewed according to WHO criteria for MIS-C. The reporting rate of this syndrome was compared to the MIS-C rate per 1,000,000 12-17-year-old children infected by SARS-CoV-2. FINDINGS: Up to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12-17-year-old children. Among them, 12 presented a hyper-inflammatory syndrome with multisystemic involvement. Main clinical features included male predominance (10/12, 83%), cardiac involvement (10/12, 83%), digestive symptoms (10/12, 83%), coagulopathy (7/12, 58%), cytolytic hepatitis (6/12, 50%), and shock (5/12, 42%). 4/12 (33%) required intensive care unit transfer, and 3/12 (25%) hemodynamic support. All cases recovered. In eight cases, no evidence of previous SARS-CoV-2 infection was found. The reporting rate was 1.5 (95%CI [0.8; 2.6]) per 1,000,000 doses injected, i.e. 2.9 (95%CI [1.5; 5.1]) per 1,000,000 12-17-year-old vaccinated children. As a comparison, 113 MIS-C (95%CI [95; 135]) occurred per 1,000,000 12-17-year-old children infected by SARS-CoV-2. INTERPRETATION: Very few cases of hyper-inflammatory syndrome with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12-17-year-old children. The low reporting rate of this syndrome, compared to the rate of post-SARS-CoV-2 MIS-C in the same age-group, largely supports the vaccination in a context of an important circulation of SARS-CoV-2. FUNDING: ESPID Fellowship Award; Grandir-Fonds de Solidarité Pour L'enfance.

Published
2022

6. Correction to 'Hyper inflammatory syndrome following COVID-19 mRNA vaccine in children: A national post-authorization pharmacovigilance study'

Author

Naïm Ouldali, Haleh Bagheri, Francesco Salvo, Denise Antona, Antoine Pariente, Claire Leblanc, Martine Tebacher, Joëlle Micallef, Corinne Levy, Robert Cohen, Etienne Javouhey, Brigitte Bader-Meunier, Caroline Ovaert, Sylvain Renolleau, Veronique Hentgen, Isabelle Kone-Paut, Nina Deschamps, Loïc De Pontual, Xavier Iriart, Christelle Gras-Le Guen, Francois Angoulvant, Alexandre Belot, Aurelie Donzeau, Layal El Aridi, Sophie Lety, Bertrand Leboucher, Agnes Baur, Lucas Jeusset, Maelle Selegny, Cristian Fedorczuk, Marion Lajus, Philippe Bensaid, Yacine Laoudi, Charlotte Pons, Anne-Cécile Robert, Camille Beaucourt, Muriel Richard, Etienne Goisque, Olivier Brissaud, Pierre Segretin, Julie Molimard, Marie-Clothilde Orecel, Gregoire Benoit, Lucille Bongiovanni, Margaux Guerder, Robin Pouyau, Jean-Marie De Guillebon De Resnes, Ellia Mezgueldi, Fleur Cour-Andlauer, Come Horvat, Pierre Poinsot, Cecile Frachette, Antoine Ouziel, Yves Gillet, Catherine Barrey, Jacques Brouard, Florence Villedieu, Vathanaksambath Ro, Narcisse Elanga, Vincent Gajdos, Romain Basmaci, Hadile Mutar, Sébastien Rouget, Elodie Nattes, Isabelle Hau, Sandra Biscardi, Houmam El Jurdi, Camille Jung, Denis Semama, Frederic Huet, Anne-Marie Zoccarato, Mayssa Sarakbi, Guillaume Mortamet, Cécile Bost-Bru, Joachim Bassil, Caroline Vinit, Véronique Hentgen, Pascal Leroux, Valérie Bertrand, Caroline Parrod, Irina Craiu, Philippe Durand, Pierre Tissiere, Caroline Claude, Guillaume Morelle, Tamazoust Guiddir, Charlotte Borocco, Frédérique Delion, Camille Guillot, Stéphane Leteurtre, François Dubos, Mylene Jouancastay, Alain Martinot, Valentine Voeusler, Jeanne Languepin, Nathalie Garrec, Arnaud Chalvon Demersay, Aurélie Morand, Emmanuelle Bosdure, Noémie Vanel, Fabrice Ughetto, Fabrice Michel, Marie Caujolle, Renaud Blonde, Jacqueline Nguyen, Olivier Vignaud, Caroline Masserot-Lureau, François Gouraud, Carine Araujo, Tara Ingrao, Sanaa Naji, Mohammed Sehaba, Christine Roche, Aurelia Carbasse, Christophe Milesi, Mustapha Mazeghrane, Sandrine Haupt, Cyril Schweitzer, Benedicte Romefort, Elise Launay, Christèle Gras-Le Guen, Ahmed Ali, Nathalie Blot, Antoine Tran, Anne Rancurel, Mickael Afanetti, Sophie Odorico, Deborah Talmud, Anais Chosidow, Anne-Sophie Romain, Emmanuel Grimprel, Marie Pouletty, Jean Gaschignard, Olivier Corseri, Albert Faye, Isabelle Melki, Camille Ducrocq, Cherine Benzoïd, Johanna Lokmer, Stéphane Dauger, Maryline Chomton, Anna Deho, Fleur Lebourgeois, Fabrice Lesage, Florence Moulin, Laurent Dupic, Yael Pinhas, Agathe Debray, Martin Chalumeau, Véronique Abadie, Pierre Frange, Jeremie F Cohen, Slimane Allali, William Curtis, Zahra Belhadjer, Johanne Auriau, Mathilde Méot, Lucile Houyel, Damien Bonnet, Christophe Delacourt, Brigitte Bader Meunier, Pierre Quartier, Youssef Shaim, Laurence Baril, Samuel Crommelynck, Baptiste Jacquot, Philippe Blanc, Natacha Maledon, Blandine Robert, Camille Loeile, Clémence Cazau, Gauthier Loron, Simona Gaga, Cécile Vittot, Loubna El Nabhani, François Buisson, Muriel Prudent, Hugues Flodrops, Fadhila Mokraoui, Simon Escoda, Laurent Bonnemains, Sarah-Louisa Mahi, Clara Mertes, Joelle Terzic, Julie Helms, Charlotte Idier, Soraya Chenichene, Nicoleta Magdolena Ursulescu, Gladys Beaujour, Abdelhak Hakim, Alice Miquel, Agnès Rey, Arnaud Wiedermann, Anne Charbonneau, Agnès Veauvy-Juven, Alexandrine Ferry, Alexis Mandelcwajg, Alix Rousseau, Amandine Prenant, Anne-Laure Bourneuf, Anne Filleron, Audrey Robine, Arthur Félix, Aude Parizel, Aurélie Labarre, Aymeric Cantais, Barbara Ros, Basile Coulon, Blandine Biot, Bérengère Dalichoux, Benjamin Fournier, Benoit Cagnard, Blandine Vanel, David Brossier, Bruno Ménager, Bruno Ozanne, Carole Marie-Jeanne, Camille Bergerot, Camille Chavy, Camille Guidon, Candice Fabre, Caroline Galeotti, Catherine Baker, Claire Ballot-Schmit, Céline Belleau, Céline Charasse, Caroline Favel, Chadia Toumi, Charlène Ferrandiz, Charlotte Couturier, Charlotte Pouchoux, Maryline Chomton-Cailliez, Charlotte Kevorkian-Verguet, Clément Brunet, Céline Manteau, Clémence Mougey, Coline Santy, Coralie Fitament, Charlotte Petriat, Charlotte Rebelle, Cyril Charron, Maxime Dartus, David Toulorge, Cécile Guillou-Debuisson, Dorann Bartebin, Valérie Klein, E Broustal, E. Desselas, Elodie Marteau, Emmanuelle Bouvrot, Elise Delacroix, Edeline Coinde, Loubna Elnabhani, Elsa Amouyal, Emilie Chaillou, Emeline Gabilly-Bernard, Emilie Ruiz, Emilie Thibault, Emilie Robin, Etienne Darrieux, Eva Blondel, Floriane Socchi, François Cazassus, Fanny Bajolle, Fatma Lacin, Fouad Madhi, Franck Zekre, François Guerin, Gerald Boussicault, Henri Ginies, Gnansounou Magloire, Guilhem Arnold, Ines Coulognon, Iona Sicard-Cras, Jean-Emmanuel Kahn, Jeanne Bordet, Jeanne-Lise Fausser, Jean-François Baleine, Josephine Brice, Julie Gendras, Kaan Pekin, Karine Norbert, Clément Karsenty, Léa Savary, Laurence Martinat, Léa Lesniewski, Lorelei Charbonnier, Louise Alexandre, Lucas Percheron, Marie Vincenti, Manon Lanzini, Margot Grisval, Marianne Mercy, Marie-Emilie Lampin, Marie Desgranges, Marie Duperril, Marie-Clothilde Orcel, Marion Audier, Marion Favier, Mathieu Carpentier, Mathilde Balcean, Mathilde Bonnet, Maurine Jouret, Marie Delattre, Michael Levy, Michael Valensi, Mickael Shum, Morgane Dumortier, Morgane Gelin, Morgane Nemmouchi, Morgane Williaume, M. Sebaha, Nicoleta Genetay-Stanescu, Nathan Giroux, Nicolas Crassard, Neil Derridj, Noemie Lachaume, Oscar Werner, Olivier Guilluy, Olivier Richer, Olivier Tirel, Aurianne Pauvert, Paul Casha, Noémie Perez, Pauline Gras, Pierre-Louis Leger, Marion Pinchou, Pierre Mornand, Prisca Largo, Ramona-Christina Ibanez, Charlotte Roulland, Salam Hadah Albarazi, Said Bichali, Sarah Faton, Amandine Schott, Sébastien Walser, Severine Guillaume, Solene Vincent, Sophie Galene-Gromez, Stanislas Kozisek, Thierry Maugard, Thierry Blanc, Thierry Navarro, Thomas Lauvray, Tamas Kovacs, Valérie Launay, Véronique Despert, Victoria Lhostis, Virginie Gall, Xavier Micaelli, Yasmine Benadjaoud, Zied Matoussi, Hélène Géniaux, Anthony Facile, Tessa Pietri, Pascale Palassin, Sylvine Pinel, Laurent Chouchana, Delphine Callot, and Charlène Boulay

Subjects
Oncology, Health Policy, Internal Medicine
Published
2022

7. Fc receptors gone wrong: A comprehensive review of their roles in autoimmune and inflammatory diseases

Author

Emilie Chalayer, Baptiste Gramont, Franck Zekre, Roman Goguyer-Deschaumes, Louis Waeckel, Lucile Grange, Stéphane Paul, Amy W. Chung, and Martin Killian

Subjects
Sjogren's Syndrome, Immunology, Infant, Newborn, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Autoimmunity, Receptors, Fc, Autoantibodies, Autoimmune Diseases
Abstract

Systemic autoimmune and inflammatory diseases have a complex and only partially known pathophysiology with various abnormalities involving all the components of the immune system. Among these components, antibodies, and especially autoantibodies are key elements contributing to autoimmunity. The interaction of antibody fragment crystallisable (Fc) and several distinct receptors, namely Fc receptors (FcRs), have gained much attention during the recent years, with possible major therapeutic perspectives for the future. The aim of this review is to comprehensively describe the known roles for FcRs (activating and inhibitory FcγRs, neonatal FcR [FcRn], FcαRI, FcεRs, Ro52/tripartite motif containing 21 [Ro52/TRIM21], FcδR, and the novel Fc receptor-like [FcRL] family) in systemic autoimmune and inflammatory disorders, namely rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, Crohn's disease, ulcerative colitis, immunoglobulin (Ig) A vasculitis, Behçet's disease, Kawasaki disease, IgG4-related disease, immune thrombocytopenia, autoimmune hemolytic anemia, antiphospholipid syndrome and heparin-induced thrombocytopenia.

Published
2022

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