title: An experimental type II mixed cryoglobulinemia with renal glomerulopathy in ICR mice triggered by Capillaria hepatica infection.
abstract: Type II mixed cryoglobulinemia is characterized by systemic vasculitis with deposition of cryoprecipitatable-immunoglobulins containing rheumatoid factor. Pathogenesis of type II mixed cryoglobulinemia has not yet been completely clarified because of the lack of an experimental animal. Here, we report an animal model of type II mixed cryoglobulinemia that is induced by experimental infection with Capillaria hepatica in ICR mice. Capillaria hepatica is a nematode that causes necrotic hepatitis in several mammals. In this study, mice experimentally infected with C. hepatica eggs developed cryoglobulinemia at 20 and 30 days post injection. Using immunological analysis, cryoglobulinemia in infected mice was classified as type II mixed cryoglobulinemia by detection of monoclonal IgM rheumatoid factor and IgA in the cryoprecipitate of serum. Using immunofluorescence, we observed an increase in the number of double-positive cells for µ heavy and κ light chains of immunoglobulin in the spleens of infected mice. Histopathologically, this model was characterized by glomerulopathy associated with intense deposition of IgM and IgA filling in capillary lumina. Ultrastructural analysis showed that glomerular deposits consisted of stacks of twisted microtubular structures. These serological and histological features resembled those of type II mixed cryoglobulinemia in human. This is the first experimental animal model of type II mixed cryoglobulinemia that will enable detailed studies on the pathogenesis of cryoglobulinemia.
authors.affiliation: Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University, Chuo-ku, Sagamihara, Kanagawa, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Aihara
authors.forename: James Kenn
authors.initials: JK
authors.lastname: Chambers
authors.forename: Kei
authors.initials: K
authors.lastname: Hosono
authors.forename: Junichi
authors.initials: J
authors.lastname: Kamiie
authors.forename: Kinji
authors.initials: K
authors.lastname: Shirota
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002195:Capillaria / Q000472:pathogenicity*; D003176:Complement C3 / Q000378:metabolism; D003449:Cryoglobulinemia / Q000209:etiology* / Q000276:immunology; D003450:Cryoglobulins / Q000378:metabolism; D004195:Disease Models, Animal; D017189:Enoplida Infections / Q000150:complications / Q000276:immunology / Q000469:parasitology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D007070:Immunoglobulin A / Q000097:blood; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D010270:Parasite Egg Count; D012217:Rheumatoid Factor / Q000097:blood; D013154:Spleen / Q000276:immunology; D013997:Time Factors
chemical_list: D003176:Complement C3; D003450:Cryoglobulins; D007070:Immunoglobulin A; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D012217:Rheumatoid Factor