These findings suggest that anti-PPM1A antibodies could be an independent biomarker of radiographic progression in AS with baseline mSASSS. Several studies have reported the association between serum biomarkers and radiographic progression in AS patients. baseline mSASSS and serum anti-PPM1A antibodies were associated with a higher risk of progression. The level of anti-PPM1A antibodies for predicting progression experienced an AUC of 0.716 (cut-off value: 43.77 ng/mL). PPM1A activation increased Atorvastatin 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 brokers. = 58)= 25)= 33)(%)47 (81)24 (96.0)23 (69.7)0.016Age (years)37.8 10.941.5 11.235 9.80.021Smoking status 0.841?Current smoker19 (32.8)9 (36)10 (30.3) ?By no means smoker25 (43.1)11 (44)14 (42.4) ?Ex-smoker14 (24.1)5 (20)9 (27.3) Disease period (months)14 (4.0C85.8)29 (3.5C124)9 (5C67.5)0.588Sacroiliitis 0.175?Grade 222 (37.9)7 (28)15 Rabbit Polyclonal to CD70 (45.5) ?Grade 3 or 436 (62.1)18 (72)18 (54.5) ESR (mm/h)54.0 34.452.4 37.555.2 32.40.759CRP (mg/dL)2.8 (0.8C6.2)2.9 (0.9C6.4)2.7 (0.8C6.2)0.654BASDAI7.5 (6.2C8.5)7.6 (5.7C8.8)7.3 (6.2C8.4)0.649BASFI5.7 (1.9C7.3)5.9 (2.0C7.6)5.0 (1.9C6.9)0.350ASDAS-CRP3.2 0.93.1 0.93.2 0.90.723mSASSS10 (6.8C24)23 (12.5C45.5)8 (5C10.5) 0.001Anti-PPM1A Abs (ng/mL)43.5 (24.9C56.3)48.9 (38.9C84.6)34.3 (21.2C50.2)0.005NSAIDs use 0.100?None4 (6.9)3 (12)1 (3) ?On demand22 (37.9)6 (24)16 (48.5) ?Regular use32 (55.2) 16 (64)16 (48.5) Anti-TNF brokers ?Infliximab27 (46.6)9 (36)18 (54.5)0.161?Etanercept14 (24.1)9 (36)5 (15.2)0.066?Golimumab13 (22.4)5 (20.0)8 (24.2)0.701?Adalimumab4 (6.9)2 (8)2 (6.1)1.000 Open in a separate window Values are offered as mean standard deviation or median (interquartile range). AS: ankylosing spondylitis, TNF: tumor necrosis factor, ESR: Erythrocyte sedimentation rate, CRP: C-reactive protein, BASDAI: Bath Ankylosing Spondylitis Disease Activity Index, BASFI: Bath Ankylosing Spondylitis Functional Index, ASDAS: ankylosing Spondylitis Disease Activity Score, mSASSS: Modified Stoke Ankylosing Spondylitis Spinal Score, PPM1A: Protein phosphatase magnesium-dependent 1A, NSAIDs: Non-steroidal anti-inflammatory drugs. 3.2. Radiographic Progression and Clinical Parameters The median follow-up mSASSS was 11.5 (7C28.5) models, and the median time to follow-up mSASSS was 22 (20C25) months. A total of 58 patients managed anti-TNF agent treatment, among whom, 43.1% (25/58) showed spinal radiographic progression (Table 1). The patients with radiographic Atorvastatin progression showed higher baseline anti-PPM1A antibody levels and baseline mSASSS than patients without radiographic progression (Table 1 and Physique 1A,B). However, the serum level of anti-PPM1A antibodies was not correlated with baseline mSASSS (r = ?0.001, = 0.993). Other baseline parameters, including ESR, CRP, BASDAI, and BASFI, were not different between the radiographic progression group and the non-progression group (Physique 1CCF). In the subgroup analysis among the patients having grade 2 sacroiliitis, baseline mSASSS was higher in the progression group than the non-progression group (= 0.03), but other baseline parameters were not different. Open in a separate window Physique 1 (A) Anti-PPM1A antibodies, (B) mSASSS, (C) ESR, (D) CRP, (E) BASDAI, and (F) BASFI at baseline in patients with radiographic progression consequently. PPM1A: Protein phosphatase magnesium-dependent 1A, mSASSS: Modified Stoke Ankylosing Spondylitis Spinal Score, ESR: Erythrocyte Sedimentation Rate, CRP: C-reactive protein, BASDAI: Bath Ankylosing Spondylitis Disease Activity Index, BASFI: Bath Ankylosing Spondylitis Functional Index. ** 0.01, *** 0.001, ns: Not significant. 3.3. Factors Associated with Spinal Radiographic Progression Logistic regression analysis was performed to evaluate the clinical factors associated with radiographic progression (Table 2). Univariate analysis indicated that male, age, baseline mSASSS, and baseline serum level of anti-PPM1A antibodies were associated with a greater risk of radiographic progression; however, being a current smoker was not associated with radiographic progression. In multivariable analysis, baseline mSASSS (OR, 1.083; 95% CI, 1.013C1.159; = 0.019) and serum level of anti-PPM1A antibodies (OR, 1.045; 95% CI, 1.011C1.080; = 0.010) were associated with spinal radiographic progression. Table 2 Factors associated with Atorvastatin radiographic progression in AS patients treated with anti-TNF brokers. 0.001) (Physique 3B). Open in a separate window Physique 3 (A) Frequency of radiographic progression, (B) odds ratio for radiographic progression categorized according to anti-PPM1A antibodies and mSASSS at baseline. Damage and high anti-PPM1A antibodies were defined as mSASSS 13 models and anti-PPM1A antibodies 43.77 ng/mL, respectively. PPM1A: Protein phosphatase magnesium-dependent 1A, Atorvastatin mSASSS: Modified Stoke Ankylosing Spondylitis Spinal Score. 3.5. PPM1A Induces Matrix Mineralization of AS-Osteoprogenitor There was no effect of exogenous PPM1A activation on ALP activity of both control- and AS-osteoprogenitors (Physique 4A). However, as shown in Physique 4B,C, AS-osteoprogenitors showed matrix mineralization features.