title: Protective role of mouse IgG1 in cryoglobulinaemia; insights from an animal model and relevance to human pathology.
abstract: Strait et al. described a novel mouse model of cryoglobulinaemia by challenging mice deficient in the immunoglobulin (Ig)G1 subclass (γ1(-) mice) with goat anti-mouse IgD [5]. The phenotype of wild-type mice was not remarkable, whereas γ1(-) mice developed IgG3 anti-goat IgG cryoglobulins as well as severe and lethal glomerulonephritis. Renal phenotype could not be rescued in γ1(-) mice by the deletion of C3, fragment crystalline γ receptor (FcγR) or J chain. On the other hand, early injection of IgG1, IgG2a or IgG2b inhibited the pathogenic effects of IgG3 in an antigen-dependent manner even in the absence of the FcγRIIb, an anti-inflammatory receptor. The authors concluded that the pathogenic role of IgG3 and the protective characteristic of IgG1 in this model were not explained by their abilities to bind to FcRs or effector molecules but are rather due to structural discrepancies enhancing the precipitation properties/solubility of IgG3/IgG1-containing immune complexes. The present article aims to discuss the current knowledge on IgG biology and the properties of IgGs explaining their differential propensity to acquire cryoglobulin activity.
authors.affiliation: INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Fire, Paris, France ELR8252 CNRS, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France AP-HP, Hôpital Bichat, Service de Néphrologie, Paris, France.
authors.forename: Jonathan Maurice
authors.initials: JM
authors.lastname: Chemouny
authors.affiliation: INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Fire, Paris, France ELR8252 CNRS, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France AP-HP, Hôpital Bichat, Départment d'Hémato-immunologie, UF Dysfonctionnements Immunitaires, Paris, France.
authors.forename: Margarita
authors.initials: M
authors.lastname: Hurtado-Nedelec
authors.affiliation: INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Fire, Paris, France ELR8252 CNRS, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France AP-HP, Hôpital Bichat, Départment d'Hémato-immunologie, UF Dysfonctionnements Immunitaires, Paris, France.
authors.forename: Héloïse
authors.initials: H
authors.lastname: Flament
authors.affiliation: INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Fire, Paris, France ELR8252 CNRS, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France AP-HP, Hôpital Bichat, Départment d'Hémato-immunologie, UF Dysfonctionnements Immunitaires, Paris, France.
authors.forename: Sanae
authors.initials: S
authors.lastname: Ben Mkaddem
authors.affiliation: INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Fire, Paris, France ELR8252 CNRS, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France AP-HP, Hôpital Bichat, Service de Néphrologie, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Daugas
authors.affiliation: INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Fire, Paris, France ELR8252 CNRS, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France AP-HP, Hôpital Bichat, Service de Néphrologie, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Vrtovsnik
authors.affiliation: INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Fire, Paris, France ELR8252 CNRS, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France.
authors.forename: Laureline
authors.initials: L
authors.lastname: Berthelot
authors.affiliation: INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Fire, Paris, France ELR8252 CNRS, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France AP-HP, Hôpital Bichat, Départment d'Hémato-immunologie, UF Dysfonctionnements Immunitaires, Paris, France.
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D003449:Cryoglobulinemia / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D051379:Mice
chemical_list: D007074:Immunoglobulin G
keywords: FcR; IgG; cryoglobulinaemia; gammopathy; review