A transgenic mouse model of autoimmune glomerulonephritis and necrotizing arteritis associated with cryoglobulinemia
| Autor: | Satoru Takahashi, Shozo Izui, Liliane Fossati-Jimack, Robert Lemoine, Thierry Fulpius, Haruyoshi Yoshida, Aki Kuroki, Shuichi Kikuchi, Luc Reininger, Kimi Araki, Yves D. Pastore |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Pathology
Mice Inbred MRL lpr Hybridomas/immunology/secretion/transplantation Autoimmune Diseases/genetics/ immunology/pathology ddc:616.07 Glomerulonephritis/genetics/ immunology/pathology Mice Glomerulonephritis Cryoglobulin Immunology and Allergy Vasculitis Leukocytoclastic Cutaneous/genetics/immunology Immunoglobulin Heavy Chains/genetics Arteritis/genetics/ immunology/pathology Cryoglobulinemia Antibodies Anti-Idiotypic Mice Inbred DBA Vasculitis Leukocytoclastic Cutaneous Antibodies Anti-Idiotypic/biosynthesis Immunoglobulin Light Chains/genetics Immunoglobulin Heavy Chains Vasculitis Injections Intraperitoneal Genetically modified mouse medicine.medical_specialty Immunology Immunoglobulin G/biosynthesis/genetics/immunology Mice Transgenic Cryoglobulins Autoantibodies/biosynthesis Autoimmune Diseases Necrosis Rheumatoid Factor medicine Rheumatoid factor Animals Cryoglobulinemia/genetics/ immunology/pathology Autoantibodies Arteritis Hybridomas business.industry Rheumatoid Factor/genetics/immunology Autoantibody medicine.disease Mice Inbred C57BL Disease Models Animal Immunoglobulin G Immunoglobulin Light Chains business |
| Zdroj: | Journal of Immunology, Vol. 169, No 8 (2002) pp. 4644-4650 |
| ISSN: | 0022-1767 |
| Popis: | Mice implanted with hybridoma secreting 6-19 IgG3 anti-IgG2a rheumatoid factor (RF) with cryoglobulin activity develop acute glomerulonephritis and cutaneous leukocytoclastic vasculitis. As the RF activity is implicated in the skin, but not glomerular lesions, it is still unclear whether the renal pathogenicity is determined by 6-19 H chains alone or their combination with L chains. To address this question, we have generated transgenic mice expressing only the H chain gene or both H and L chain genes of the 6-19 IgG3 anti-IgG2a RF and determined the development of glomerular and vascular lesions. H-single and H/L-double transgenic mice displayed comparable high amounts of IgG3 cryoglobulins, but only H/L-double transgenic mice having 10-fold higher levels of IgG3 anti-IgG2a RF progressively developed chronic, lethal glomerulonephritis. The severe glomerular lesions observed at 8–10 mo of age were very heterogeneous (membranoproliferative changes, crescents, and sclerosis); in addition, one-third of them had necrotizing arteritis in the kidneys and skeletal muscles. These renal and vascular changes were very different from those observed in the acute cryoglobulinemia, characterized by mainly “wire-loop” glomerular lesions and a cutaneous leukocytoclastic form of vasculitis. Thus, our data demonstrate the importance of a unique combination of the H and L chains for the expression of the pathogenic activity of IgG3 cryoglobulins and that a single autoantibody is able to induce different types of glomerular and vascular complications, depending on its production levels and kinetics. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|