Immunization with glucose-6-phosphate isomerase induces T cell-dependent peripheral polyarthritis in genetically unaltered mice.

Abstract

Rheumatoid arthritis is a chronic inflammatory disease primarily affecting the joints. The search for arthritogenic autoantigens that trigger autoimmune responses in rheumatoid arthritis has largely focused on cartilage- or joint-specific Ags. In this study, we show that immunization with the ubiquitously expressed glycolytic enzyme glucose-6-phosphate isomerase (G6PI) induces severe peripheral symmetric polyarthritis in normal mice. In genetically unaltered mice, T cells are indispensable for both the induction and the effector phase of G6PI-induced arthritis. Arthritis is cured by depletion of CD4(+) cells. In contrast, Abs and FcgammaR(+) effector cells are necessary but not sufficient for G6PI-induced arthritis in genetically unaltered mice. Thus, the complex pathogenesis of G6PI-induced arthritis in normal mice differs strongly from the spontaneously occurring arthritis in the transgenic K/B x N model where Abs against G6PI alone suffice to induce the disease. G6PI-induced arthritis demonstrates for the first time the induction of organ-specific disease by systemic autoimmunity in genetically unaltered mice. Both the induction and effector phase of arthritis induced by a systemic autoimmune response can be dissected and preventive and therapeutic strategies evaluated in this model.

• Authors: David Schubert, Bert Maier, Lars Morawietz, Veit Krenn, Thomas Kamradt
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 172 Issue 7 Pg. 4503-9 (Apr 01 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15034067 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Blocking
• Autoantibodies
• Autoantigens
• CD4 Antigens
• Tumor Necrosis Factor-alpha
• Glucose-6-Phosphate Isomerase

Topics

• Animals
• Antibodies, Blocking (administration & dosage)
• Arthritis, Experimental (enzymology, genetics, immunology, therapy)
• Autoantibodies (biosynthesis, physiology)
• Autoantigens (administration & dosage, immunology)
• CD4 Antigens (biosynthesis, immunology)
• Genetic Predisposition to Disease
• Glucose-6-Phosphate Isomerase (administration & dosage, immunology)
• Humans
• Immunity, Cellular (genetics)
• Immunity, Innate (genetics)
• Immunization (methods)
• Injections, Intraperitoneal
• Injections, Subcutaneous
• Lymphocyte Depletion
• Mice
• Mice, Inbred AKR
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Knockout
• T-Lymphocyte Subsets (immunology)
• Tumor Necrosis Factor-alpha (physiology)