Autoantibodies against Protein Phosphatase Magnesium-Dependent 1A as a Biomarker for Predicting Radiographic Progression in Ankylosing Spondylitis Treated with Anti-Tumor Necrosis Factor Agents

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.