title: Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients.
abstract: Using 2-dimensional electrophoresis and ion-pair chromatography, we have identified elements of proliferating cell nuclear antigen (PCNA) multiprotein complexes that are reactive to antibodies in sera from patients with systemic lupus erythematosus. Among the various elements of the complexes, a 37 kDa protein (PI 8.5) that specifically reacted with SLE sera, but not with sera from patients with other connective tissue diseases, was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Immunoblot analysis showed that SLE sera reactive with the 37 kDa protein specifically reacted with GAPDH, as did anti-GAPDH mAbs. The purified autoantibodies to GAPDH from lupus serum showed both nuclear speckled and cytoplasmic staining patterns in immunofluorescence on Hep-2 cells. In addition, enzyme-linked immunosorbent assay (ELISA) revealed the presence of anti-GAPDH autoantibodies in 47% of lupus patients. Longitudinal analysis of the reactivity of lupus sera to PCNA complexes showed the autoimmune response to spread from GAPDH to other elements of PCNA complexes, and the presence of anti-GAPDH antibodies was significantly correlated with increased levels of serum PCNA. Taken together, these findings suggest that GAPDH interacting with PCNA in association with its cellular function is a novel autoantigen recognized by lupus sera, and that GAPDH thus plays an important role in the induction of autoimmune responses against the PCNA complex.
authors.affiliation: Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo 113-8421, Japan. tyoshi@med.juntendo.ac.jp
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Takasaki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kaneda
authors.forename: Masakazu
authors.initials: M
authors.lastname: Matsushita
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamada
authors.forename: Masuyuki
authors.initials: M
authors.lastname: Nawata
authors.forename: Ran
authors.initials: R
authors.lastname: Matsudaira
authors.forename: Masanao
authors.initials: M
authors.lastname: Asano
authors.forename: Reiko
authors.initials: R
authors.lastname: Mineki
authors.forename: Noriko
authors.initials: N
authors.lastname: Shindo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology*; D003240:Connective Tissue Diseases / Q000276:immunology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D018809:Proliferating Cell Nuclear Antigen; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases