title: Decreased levels of autoantibody against histone deacetylase 3 in patients with systemic sclerosis.
abstract: Systemic sclerosis (SSc) is characterized by immunological abnormalities, especially the production of autoantibodies against various cellular components. Treatment with histone deacetylase (HDAC) inhibitors prevents collagen accumulation in a mouse SSc model. Additionally, autoantibody against HDAC-3 is produced in colon cancer patients, while HDAC-1 and HDAC-2 do not elicit autoantibody response. To determine the presence and levels of antibodies (Abs) against HDAC-3 in SSc. Anti-HDAC-3 Ab was examined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting using human recombinant HDAC-3. The HDAC-3 activity was evaluated by ELISA using the fluorimetric HDAC lysyl substrate that comprises an acetylated lysine side chain. Contrary to our hypothesis that autoimmune background in SSc induced the production of autoantibody against HDACs, IgG and IgM anti-HDAC-3 Ab levels in SSc patients were significantly lower than in normal controls (p < 0.0005 and 0.001, respectively). Furthermore, decreased levels of IgG anti-HDAC-3 Ab were specific to SSc, since IgG anti-HDAC-3 Ab levels in patients with dermatomyositis (DM) and those with systemic lupus erythematosus (SLE) were similar and slightly increased relative to normal controls, respectively. Immunoblotting analysis showed that anti-HDAC-3 Ab was detected in normal controls and patients with DM or SLE, while it was absent in SSc patients. The HDAC-3 activity was significantly inhibited by IgG isolated from sera of normal controls, whereas such inhibitory effect was not observed by IgG isolated from sera of SSc patients. These results indicate the lack of anti-HDAC-3 autoantibody in SSc patients, which is produced in healthy individuals as well as DM and SLE patients, suggesting that this autoantibody might function as protective Ab.
authors.affiliation: Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kuwatsuka
authors.forename: Fumihide
authors.initials: F
authors.lastname: Ogawa
authors.forename: Yohei
authors.initials: Y
authors.lastname: Iwata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Komura
authors.forename: Eiji
authors.initials: E
authors.lastname: Muroi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Hara
authors.forename: Motoi
authors.initials: M
authors.lastname: Takenaka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shimizu
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D003882:Dermatomyositis / Q000097:blood / Q000276:immunology; D005260:Female; D006655:Histone Deacetylases / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000097:blood* / Q000276:immunology*; D000099186:Histone Deacetylase 3
chemical_list: D001323:Autoantibodies; D006655:Histone Deacetylases; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D000099186:Histone Deacetylase 3