title: Intravenous immunoglobulin-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients.
abstract: Intravenous immunoglobulin (IVIg) is used in the therapy of various autoimmune and inflammatory diseases. Recent studies in experimental models propose that anti-inflammatory effects of IVIg are mainly mediated by α2,6-sialylated Fc fragments. These reports further suggest that α2,6-sialylated Fc fragments interact with DC-SIGN(+) cells to release IL-33 that subsequently expands IL-4-producing basophils. However, translational insights on these observations are lacking. Here we show that IVIg therapy in rheumatic patients leads to significant raise in plasma IL-33. However, IL-33 was not contributed by human DC-SIGN(+) dendritic cells and splenocytes. As IL-33 has been shown to expand basophils, we analyzed the proportion of circulating basophils in these patients following IVIg therapy. In contrast to mice data, IVIg therapy led to basophil expansion only in two patients who also showed increased plasma levels of IL-33. Importantly, the fold-changes in IL-33 and basophils were not correlated and we could hardly detect IL-4 in the plasma following IVIg therapy. Thus, our results indicate that IVIg-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients. Hence, IL-33 and basophil-mediated anti-inflammatory mechanism proposed for IVIg might not be pertinent in humans.
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France [2] Université de Technologie de Compiègne, Compiègne, F-60205, France.
authors.forename: Meenu
authors.initials: M
authors.lastname: Sharma
authors.affiliation: 1] Département de Médecine Interne et Immunologie Clinique, Centre de référence maladies neuro-musculaires, Hôpital Pitié-Salpêtrière, AP-HP, Paris F-75013, France [2] Université Pierre et Marie Curie -Paris 6, F-75013, France.
authors.forename: Yoland
authors.initials: Y
authors.lastname: Schoindre
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Hegde
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France [2] Université de Technologie de Compiègne, Compiègne, F-60205, France.
authors.forename: Chaitrali
authors.initials: C
authors.lastname: Saha
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France [2] Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Université Pierre et Marie Curie - Paris 6, UMR S 1138, 15 rue de l'Ecole de Médicine, Paris, F-75006, France.
authors.forename: Mohan S
authors.initials: MS
authors.lastname: Maddur
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France [2] Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Université Pierre et Marie Curie - Paris 6, UMR S 1138, 15 rue de l'Ecole de Médicine, Paris, F-75006, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Stephen-Victor
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France [2] Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Université Pierre et Marie Curie - Paris 6, UMR S 1138, 15 rue de l'Ecole de Médicine, Paris, F-75006, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gilardin
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France [2] Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Université Pierre et Marie Curie - Paris 6, UMR S 1138, 15 rue de l'Ecole de Médicine, Paris, F-75006, France [3] Université Paris Descartes, UMR S 1138 Paris, F-75006, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Lecerf
authors.affiliation: Service d'anatomie pathologique, Hôpital Européen Georges Pompidou, Paris, F-75015, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.affiliation: 1] Institut Cochin, Institut National de la Santé et de la Recherche Médicale Unité 1016, CNRS UMR 8104, Université Paris Descartes, F-75014, France [2] Pôle de Médecine Interne, Centre de Référence pour les maladies systémiques autoimmunes rares; Assistance Publique-Hôpitaux de Paris (AP-HP); Paris, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
authors.affiliation: 1] Département de Médecine Interne et Immunologie Clinique, Centre de référence maladies neuro-musculaires, Hôpital Pitié-Salpêtrière, AP-HP, Paris F-75013, France [2] Université Pierre et Marie Curie -Paris 6, F-75013, France [3] Institut National de la Santé et de la Recherche Médicale Unité 974, Paris, F-75013, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Benveniste
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France [2] Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Université Pierre et Marie Curie - Paris 6, UMR S 1138, 15 rue de l'Ecole de Médicine, Paris, F-75006, France [3] Université Paris Descartes, UMR S 1138 Paris, F-75006, France [4] International Associated Laboratory IMPACT (Institut National de la Santé et de la Recherche Médicale, France - Indian council of Medical Research, India), National Institute of Immunohaematology, Mumbai, 400012, India.
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France [2] Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Université Pierre et Marie Curie - Paris 6, UMR S 1138, 15 rue de l'Ecole de Médicine, Paris, F-75006, France [3] Université Paris Descartes, UMR S 1138 Paris, F-75006, France [4] International Associated Laboratory IMPACT (Institut National de la Santé et de la Recherche Médicale, France - Indian council of Medical Research, India), National Institute of Immunohaematology, Mumbai, 400012, India.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism*; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; C506536:IL33 protein, human; D016756:Immunoglobulins, Intravenous; D000067596:Interleukin-33; D007378:Interleukins; D015847:Interleukin-4