Circulating mir-99b-5p as a predictor of erosion progression in early rheumatoid arthritis: a 1-year follow-up study by hr-pqct
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AbstractBackground: Bone erosion is a key feature of RA reflecting both disease severity and progression. HR-pQCT is an in-vivo clinical imaging system allowing detailed analysis of bone structure, including bone erosion. Several circulating microRNAs have already been suggested as potential biomarkers in RA.
Objectives: To determine whether plasma cell-free circulating miRNAs are 1) associated with bone erosion at presentation and 2) predictive of erosion progression at 12 months as determined by HR-pQCT in patients with early rheumatoid arthritis (ERA).
Methods: In this prospective study, 124 ERA patients were treated with a tight control protocol aiming at remission by using conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). The second metacarpophalangeal joint (MCP2) was assessed for erosions by HR-pQCT at baseline and after 12 months. Plasma cell-free circulating miRNAs at baseline were identified by microRNA array in 10 treatment-naïve ERA patients with maximal erosion volume at MCP2; in 10 treatment-naïve ERA patients without erosion; and in 6 age- and sex-matched healthy controls. The 4 most dysregulated miRNAs were identified by TaqMan® qRT-PCR in these same 20 ERA patients. Thereafter, the expression of these 4 selected miRNAs was validated in all 124 ERA patients at baseline.
Results: Of the 377 screened miRNAs, 155 miRNAs were detectable. 94 (60.6%) of these detectable miRNAs were upregulated in ERA patient with erosions, with 13 (8.4%) upregulated more than twofold. 61 (39.4%) miRNAs were downregulated in ERA patients with erosions, with 6 (3.9%) downregulated more than twofold. A total of 16 miRNAs were differentially expressed (P<0.05) and 4 were possibly differentially expressed (P ≤0.1) between ERA patients with and without erosions. At baseline, expressions of miR-143–3p, miR-145–5p and miR-99b-5p were significantly higher in ERA patients with erosions than those without erosions (P<0.05 for all). After 12 months of csDMARDs treatment, 31.7%, 47.7%, and 20.6% of the ERA patients had erosion progression, stable erosion and partial erosion repair respectively. Logistic regression analysis revealed baseline expression of miR-99b-5p to be an independent predictor of erosion progression at 12 months (Exp [B]= 4.203, 95% CI 1.166–15.147, P=0.028) (table 1).
Objectives: To determine whether plasma cell-free circulating miRNAs are 1) associated with bone erosion at presentation and 2) predictive of erosion progression at 12 months as determined by HR-pQCT in patients with early rheumatoid arthritis (ERA).
Methods: In this prospective study, 124 ERA patients were treated with a tight control protocol aiming at remission by using conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). The second metacarpophalangeal joint (MCP2) was assessed for erosions by HR-pQCT at baseline and after 12 months. Plasma cell-free circulating miRNAs at baseline were identified by microRNA array in 10 treatment-naïve ERA patients with maximal erosion volume at MCP2; in 10 treatment-naïve ERA patients without erosion; and in 6 age- and sex-matched healthy controls. The 4 most dysregulated miRNAs were identified by TaqMan® qRT-PCR in these same 20 ERA patients. Thereafter, the expression of these 4 selected miRNAs was validated in all 124 ERA patients at baseline.
Results: Of the 377 screened miRNAs, 155 miRNAs were detectable. 94 (60.6%) of these detectable miRNAs were upregulated in ERA patient with erosions, with 13 (8.4%) upregulated more than twofold. 61 (39.4%) miRNAs were downregulated in ERA patients with erosions, with 6 (3.9%) downregulated more than twofold. A total of 16 miRNAs were differentially expressed (P<0.05) and 4 were possibly differentially expressed (P ≤0.1) between ERA patients with and without erosions. At baseline, expressions of miR-143–3p, miR-145–5p and miR-99b-5p were significantly higher in ERA patients with erosions than those without erosions (P<0.05 for all). After 12 months of csDMARDs treatment, 31.7%, 47.7%, and 20.6% of the ERA patients had erosion progression, stable erosion and partial erosion repair respectively. Logistic regression analysis revealed baseline expression of miR-99b-5p to be an independent predictor of erosion progression at 12 months (Exp [B]= 4.203, 95% CI 1.166–15.147, P=0.028) (table 1).
All Author(s) ListJ.Yue, J. F. Griffith, J. Xu, F. Xiao, L. Shi, D. Wang, P. C. Wong, E. K. Li, M. Li, T. K. Li, T. Y. Zhu, V. Hung, L. Qin, L.-S. Tam
Name of ConferenceAnnual European Congress of Rheumatology
Start Date of Conference13/06/2018
End Date of Conference16/06/2018
Place of ConferenceAmsterdam
Country/Region of ConferenceNetherlands
Proceedings TitleAnnals of the Rheumatic Diseases - Annual European Congress of Rhemmatology
Year2018
Month6
Volume Number77
Issue NumberSupplement 2
PublisherBMJ
LanguagesEnglish-United Kingdom