Role of protein phosphatase magnesium-dependent 1a and anti-protein phosphatase magnesium-dependent 1A autoantibodies in ankylosing spondylitis

Yong Gil Kim, Dong Hyun Sohn, Xiaoyan Zhao, Jeremy Sokolove, Tamsin M. Lindstrom, Bin Yoo, Chang Keun Lee, John D. Reveille, Joel D. Taurog, William H. Robinson

Research output: Contribution to journalArticle

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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.

Conclusion Anti-PPM1A autoantibodies are present in AS, and our findings suggest that PPM1A may contribute to the pathogenic bone ankylosis characteristic of AS.

Original languageEnglish (US)
Pages (from-to)2793-2803
Number of pages11
JournalArthritis and Rheumatology
Volume66
Issue number10
DOIs
StatePublished - Oct 1 2014

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Phosphoprotein Phosphatases
Ankylosing Spondylitis
Autoantibodies
Magnesium
Transgenic Rats
Serum
Osteoblasts
Baths
Tumor Necrosis Factor-alpha
Sacroiliitis
Gene Knockdown Techniques
Ankylosis
HLA-B27 Antigen
Protein Array Analysis
Antibodies
Osteoarthritis
Rheumatoid Arthritis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Medicine(all)

Cite this

Role of protein phosphatase magnesium-dependent 1a and anti-protein phosphatase magnesium-dependent 1A autoantibodies in ankylosing spondylitis. / Kim, Yong Gil; Sohn, Dong Hyun; Zhao, Xiaoyan; Sokolove, Jeremy; Lindstrom, Tamsin M.; Yoo, Bin; Lee, Chang Keun; Reveille, John D.; Taurog, Joel D.; Robinson, William H.

In: Arthritis and Rheumatology, Vol. 66, No. 10, 01.10.2014, p. 2793-2803.

Research output: Contribution to journalArticle

Kim, YG, Sohn, DH, Zhao, X, Sokolove, J, Lindstrom, TM, Yoo, B, Lee, CK, Reveille, JD, Taurog, JD & Robinson, WH 2014, 'Role of protein phosphatase magnesium-dependent 1a and anti-protein phosphatase magnesium-dependent 1A autoantibodies in ankylosing spondylitis', Arthritis and Rheumatology, vol. 66, no. 10, pp. 2793-2803. https://doi.org/10.1002/art.38763
Kim, Yong Gil ; Sohn, Dong Hyun ; Zhao, Xiaoyan ; Sokolove, Jeremy ; Lindstrom, Tamsin M. ; Yoo, Bin ; Lee, Chang Keun ; Reveille, John D. ; Taurog, Joel D. ; Robinson, William H. / Role of protein phosphatase magnesium-dependent 1a and anti-protein phosphatase magnesium-dependent 1A autoantibodies in ankylosing spondylitis. In: Arthritis and Rheumatology. 2014 ; Vol. 66, No. 10. pp. 2793-2803.
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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.Conclusion Anti-PPM1A autoantibodies are present in AS, and our findings suggest that PPM1A may contribute to the pathogenic bone ankylosis characteristic of AS.",
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T1 - Role of protein phosphatase magnesium-dependent 1a and anti-protein phosphatase magnesium-dependent 1A autoantibodies in ankylosing spondylitis

AU - Kim, Yong Gil

AU - Sohn, Dong Hyun

AU - Zhao, Xiaoyan

AU - Sokolove, Jeremy

AU - Lindstrom, Tamsin M.

AU - Yoo, Bin

AU - Lee, Chang Keun

AU - Reveille, John D.

AU - Taurog, Joel D.

AU - Robinson, William H.

PY - 2014/10/1

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N2 - 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.Conclusion Anti-PPM1A autoantibodies are present in AS, and our findings suggest that PPM1A may contribute to the pathogenic bone ankylosis characteristic of AS.

AB - 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.Conclusion Anti-PPM1A autoantibodies are present in AS, and our findings suggest that PPM1A may contribute to the pathogenic bone ankylosis characteristic of AS.

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