Jung-Sun Lee1, Eun-Ju Lee2, Jae-Hyun Lee2, Seok-Chan Hong2, Chang-Keun Lee2, Bin Yoo2, Ji-Seon Oh3, Sang-Hoon Lee4, Tae-Jong Kim5, Seung-Hun Lee6, Sung-Sin Jo7, Dae-Hyun Yoo8, Ye-Soo Park9, Tae-Hwan Kim8, Yong-Gil Kim2. 1. Division of Rheumatology, Department of Internal Medicine, Seoul Veterans Hospital, Seoul 05368, Korea. 2. Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Korea. 3. Department of Information Medicine, Asan Medical Center, Seoul 05505, Korea. 4. Department of Rheumatology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul 05278, Korea. 5. Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju 61469, Korea. 6. Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul 04763, Korea. 7. Hanyang University Institute for Rheumatology Research, Seoul 04763, Korea. 8. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 04763, Korea. 9. Department of Orthopedic Surgery, Hanyang University Hospital, Guri 11923, Korea.
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.
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.
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