title: Role of protein phosphatase magnesium-dependent 1A and anti-protein phosphatase magnesium-dependent 1A autoantibodies in ankylosing spondylitis.
abstract: OBJECTIVE
  Although ankylosing spondylitis (AS) is driven by immune-mediated processes, little is known about the presence and role of autoantibodies in this disease. This study was undertaken to investigate whether autoantibodies occur in and are involved in AS.
  
  
  METHODS
  We performed human protein microarray analysis of sera derived from patients with AS or other autoimmune disorders to identify autoantibodies associated specifically with AS, and identified autoantibody targeting of protein phosphatase magnesium-dependent 1A (PPM1A) in AS. We performed enzyme-linked immunosorbent assay (ELISA) analysis of sera from 2 independent AS cohorts to confirm autoantibody targeting of PPM1A, and to assess associations between levels of anti-PPM1A antibodies and AS disease severity or response to anti-tumor necrosis factor (anti-TNF) therapy (as measured by Bath AS Disease Activity Index [BASDAI] score). Levels of anti-PPM1A antibodies were also evaluated in sera from rats transgenic for HLA-B27 and human β2 -microglobulin. The expression of PPM1A was assessed by immunohistochemistry in synovial tissue samples from patients with AS, rheumatoid arthritis, or osteoarthritis. The role of PPM1A in osteoblast differentiation was investigated by gene knockdown and overexpression.
  
  
  RESULTS
  AS was associated with autoantibody targeting of PPM1A, and levels of anti-PPM1A autoantibodies were significantly higher in patients with more advanced sacroiliitis and correlated positively with BASDAI score after treatment with anti-TNF agents. The levels of anti-PPM1A autoantibodies were also higher in the sera of transgenic rats that are prone to develop spondyloarthritis than in those that are not. PPM1A was expressed in AS synovial tissue, and PPM1A overexpression promoted osteoblast differentiation, whereas PPM1A knockdown suppressed it.
  
  
  CONCLUSIONS
  Anti-PPM1A autoantibodies are present in AS, and our findings suggest that PPM1A may contribute to the pathogenic bone ankylosis characteristic of AS.
authors: Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.|VA Palo Alto Health Care System, Palo Alto, California, USA.|Division of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors: Yong-Gil
authors: YG
authors: Kim
authors: Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.|VA Palo Alto Health Care System, Palo Alto, California, USA.
authors: Dong Hyun
authors: DH
authors: Sohn
authors: Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.|VA Palo Alto Health Care System, Palo Alto, California, USA.
authors: Xiaoyan
authors: X
authors: Zhao
authors: Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.|VA Palo Alto Health Care System, Palo Alto, California, USA.
authors: Jeremy
authors: J
authors: Sokolove
authors: Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.
authors: Tamsin M
authors: TM
authors: Lindstrom
authors: Division of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors: Bin
authors: B
authors: Yoo
authors: Division of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors: Chang-Keun
authors: CK
authors: Lee
authors: Division of Rheumatology, University of Texas Health Sciences Center, Houston, Texas, USA.
authors: John D
authors: JD
authors: Reveille
authors: Rheumatic Diseases Division, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors: Joel D
authors: JD
authors: Taurog
authors: Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.|VA Palo Alto Health Care System, Palo Alto, California, USA.
authors: William H
authors: WH
authors: Robinson
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000276:immunology*; D000071636:Protein Phosphatase 2C; D051381:Rats; D055647:Rats, Transgenic; D058566:Sacroiliitis / Q000097:blood / Q000276:immunology*; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology
chemical_list: D001323:Autoantibodies; C000607456:PPM1A protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C