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

抗蛋白磷酸酶镁依赖性 1A 自身抗体作为预测抗肿瘤坏死因子药物治疗强直性脊柱炎的放射学进展的生物标志物

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作者:Jung-Sun Lee, Eun-Ju Lee, Jae-Hyun Lee, Seok-Chan Hong, Chang-Keun Lee, Bin Yoo, Ji-Seon Oh, Sang-Hoon Lee, Tae-Jong Kim, Seung-Hun Lee, Sung-Sin Jo, Dae-Hyun Yoo, Ye-Soo Park, Tae-Hwan Kim, Yong-Gil Kim

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.

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.

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.

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