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Title: Correlation of serum MMP3 and other biomarkers with clinical outcomes in patients with ankylosing spondylitis: A pilot study

item HE, DONGYI - Shanghai Guanghua Hospital
item ZHU, QU - Shanghai Guanghua Hospital
item ZHOU, QUAN - Children'S Nutrition Research Center (CNRC)
item QI, QING - University Of Texas Health Science Center
item SUN, HONGMEI - Shanghai Guanghua Hospital
item ZACHARIAH, LIZA - University Of Texas Health Science Center
item WANG, GRACE - Washington University
item REVEILLE, JOHN - University Of Texas Health Science Center
item GUAN, YONGTAO - Children'S Nutrition Research Center (CNRC)
item ZHOU, XIAODONG - University Of Texas Health Science Center

Submitted to: Clinical Rheumatology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/31/2017
Publication Date: 4/22/2017
Citation: He, D., Zhu, Q., Zhou, Q., Qi, Q., Sun, H., Zachariah, L.M., Wang, G., Reveille, J.D., Guan, Y., Zhou, X. 2017. Correlation of serum MMP3 and other biomarkers with clinical outcomes in patients with ankylosing spondylitis: A pilot study. Clinical Rheumatology. doi:10.1007/s10067-017-3624-7.

Interpretive Summary: Researchers desire to know if metabolites can reliably predict long term prognosis of patients with autoimmune diseases. In this pilot study, we provided an affirmative answer. Using serum biomarker such as proteins of the matrix metalloproteinase family, our pilot study showed that the clinical outcomes of patients with an autoimmune disease ankylosing spondylitis can be faithfully predicted. This study is valuable since metabolites can be strongly influenced by nutrition intake. Although the subjects of this study are adults, the knowledge and methodology can be applied to children as well.

Technical Abstract: The studies aimed to assess a set of biomarkers for their correlations with disease activity/severity of patients with ankylosing spondylitis (AS). A total of 24 AS patients were treated with etanercept and prospectively followed for 12 weeks. Serum levels of TNF-alpha, IFN-gamma, TGF-beta, IL6, IL15, IL17, MMP3, and MICA were measured at baseline and after treatment. The change of these biomarkers was analyzed for correlations with MRI indices for joint inflammation, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, AS Disease Activity Score, serum CRP, and ESR. The Wilcoxon rank sum test was used to compare the biomarker levels between pre- and post-treatment and between pre-treatment and controls. Both step-wise procedures based on the Akaike information criterion (AIC) and least absolute shrinkage and selection operator with fivefold cross-validation were used to select the best model for pairwise correlations between the above clinical measures and the serum biomarkers. Serum levels of both MMP3 and IL6 were significantly higher in AS patients at baseline. After treatment, the levels of MMP3 decreased, but TGF-beta and TNF-alpha increased significantly. The changes of serum MMP3 and MICA were significantly associated with MRI sacroiliac joint (SIJ) scores. CRP was positively correlated with serum MMP3 and IL6. The pattern of combined changes of serum MICA, MMP3, TGF-beta, IL17, TNF-alpha, and IFN-gamma predicted the MRI score of SIJ by logistic regression analysis. Specific serum biomarkers were significantly associated with clinical measures of AS. Most prominently, serum MMP3 level was found to have a positive correlation with the MRI score of SIJ and CRP. Serum MICA level negatively correlated with disease remission.