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10.1002/art.38763

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suck abstract from ncbi


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pmid24980965
      Arthritis+Rheumatol 2014 ; 66 (10 ): 2793-2803
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  • Role of protein phosphatase magnesium-dependent 1A and anti-protein phosphatase magnesium-dependent 1A autoantibodies in ankylosing spondylitis #MMPMID24980965
  • Kim YG ; Sohn DH ; Zhao X ; Sokolove J ; Lindstrom TM ; Yoo B ; Lee CK ; Reveille JD ; Taurog JD ; Robinson WH
  • Arthritis Rheumatol 2014[Oct]; 66 (10 ): 2793-2803 PMID24980965 show ga
  • 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 ?2 -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. CONCLUSION: Anti-PPM1A autoantibodies are present in AS, and our findings suggest that PPM1A may contribute to the pathogenic bone ankylosis characteristic of AS.
  • |Animals [MESH]
  • |Autoantibodies/*blood [MESH]
  • |Humans [MESH]
  • |Phosphoprotein Phosphatases/*immunology [MESH]
  • |Protein Phosphatase 2C [MESH]
  • |Rats [MESH]
  • |Rats, Transgenic [MESH]
  • |Sacroiliitis/blood/*immunology [MESH]
  • |Severity of Illness Index [MESH]
  • |Spondylitis, Ankylosing/blood/*immunology [MESH]


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