title: A glucose-6-phosphate isomerase peptide induces T and B cell-dependent chronic arthritis in C57BL/10 mice: arthritis without reactive oxygen species and complement.
abstract: Immunization with human glucose-6-phosphate isomerase (hG6PI) protein or with several of its peptides induces arthritis in DBA/1 mice. We investigated G6PI peptide-induced arthritis in C57BL/10 mice and the effect of oxidative burst on disease. To study the arthritogenicity of G6PI peptides and its immune dependency, we used genetically modified and congenic mice on the C57BL/10 background and in vitro T- and B-cell assays. hG6PI(325-339) peptide induced arthritis in C57BL/10 mice. The disease was associated with major histocompatibility complex class II and was dependent on T cells, B cells, and complement C5. Th1 and Th17 cells primed with the hG6PI(325-339) peptide cross-reacted with the murine G6PI protein. The severity of the disease increased in mice carrying a mutation in Ncf1 (Ncf1*/*), which abolishes the NADPH oxidase 2 complex oxidative burst. Ncf1*/* mice developed arthritis also on immunization with the mouse G6PI325-339 peptide and in the absence of C5. The antibody responses to the G6PI protein and peptides were minimal in both Ncf1*/* and wild-type mice. Herein is described G6PI peptide as the first peptide to induce arthritis in C57BL/10 mice. The differences between the wild-type and Ncf1*/* mice suggest that an alternative complement-independent arthritogenic pathway could be operative in the absence of oxidative burst.
authors.affiliation: Division of Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Angela
authors.initials: A
authors.lastname: Pizzolla
authors.affiliation: Division of Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kajsa
authors.initials: K
authors.lastname: Wing
authors.affiliation: Division of Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Electronic address: Rikard.Holmdahl@ki.se.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000596:Amino Acids / Q000235:genetics; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D003165:Complement System Proteins / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D019255:NADPH Oxidases / Q000378:metabolism; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000596:Amino Acids; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D010455:Peptides; D017382:Reactive Oxygen Species; D003165:Complement System Proteins; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; C554959:GPI protein, human; D005956:Glucose-6-Phosphate Isomerase