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Am J Pathol. 2013 Oct;183(4):1144-1155. doi: 10.1016/j.ajpath.2013.06.019. Epub 2013 Jul 30.

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.

Author information

1
Division of Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
2
Division of Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Electronic address: Rikard.Holmdahl@ki.se.

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.

PMID:
23911657
DOI:
10.1016/j.ajpath.2013.06.019
[Indexed for MEDLINE]

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