Abstract
Background: Patients with ankylosing spondylitis (AS) have increased levels of protein phosphatase magnesium-dependent 1A (PPM1A) and autoantibodies. We evaluated the usefulness of serum anti-PPM1A antibodies as a biomarker for AS. Methods: Serum samples from 58 AS patients were obtained from a multicenter registry prior to the initiation of anti-TNF agents. The serum levels of anti-PPM1A antibodies were measured using ELISA. Spinal radiographic progression was defined as an increase in the modified stoke ankylosing spondylitis spinal score (mSASSS) by ≥2 units or a newly developed syndesmophyte. The role of exogenous PPM1A on bone mineralization was evaluated using primary osteoprogenitors acquired from patients with AS and non-inflammatory controls. Results: The baseline levels of anti-PPM1A antibodies and mSASSS were higher in the radiographic progression group than in the non-progression group. In logistic regression analysis, baseline mSASSS and serum anti-PPM1A antibodies were associated with a higher risk of progression. The level of anti-PPM1A antibodies for predicting progression had an AUC of 0.716 (cut-off value: 43.77 ng/mL). PPM1A stimulation increased matrix mineralization in AS-osteoprogenitors but not in controls. Conclusion: Along with mSASSS, the serum levels of anti-PPM1A antibodies might be useful as a predictor of radiographic progression after treatment with anti-TNF agents.
Highlights
Ankylosing spondylitis (AS) is chronic inflammatory arthritis characterized by ankylosis of the spine and sacroiliac joint [1]
Receiver operating characteristics (ROC) analysis was used to determine the predictive value of factors that were associated with spinal radiographic progression
The serum level of anti-phosphatase magnesium-dependent 1A (PPM1A) antibodies had an area under the curve (AUC) of 0.716 at a cut-off value of 43.77 ng/mL
Summary
Ankylosing spondylitis (AS) is chronic inflammatory arthritis characterized by ankylosis of the spine and sacroiliac joint [1]. Since AS structural damage is irreversible, biomarker detection at the early stages of the disease will be important to identify patients who are at the most risk of developing structural damage. Our previous study reported that the serum levels of anti-PPM1A antibodies are higher in AS than in other autoimmune diseases [10]. The serum levels of anti-PPM1A antibodies were higher in AS patients with high-grade sacroiliitis than those with low-grade sacroiliitis. Anti-PPM1A antibodies have not yet been implicated clinically because the levels were not measured quantitatively. We developed a method for quantitative measurement of the serum anti-PPM1A antibody levels and evaluated the usefulness of serum anti-PPM1A antibodies as a biomarker of spinal progression in AS patients beginning treatment with anti-TNF agents
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