Serum lncRNA ITGB2-AS1 and ICAM-1 as novel biomarkers for rheumatoid arthritis and osteoarthritis diagnosis.

Abstract

BACKGROUND: The complete circulating long non-coding RNAs (lncRNAs) signature of rheumatoid arthritis (RA) and osteoarthritis (OA) is still uncovered. The lncRNA integrin subunit beta 2 (ITGB2)-anti-sense RNA 1 (ITGB2-AS1) affects ITGB2 expression; however, there is a gap in knowledge regarding its expression and clinical usefulness in RA and OA. This study investigated the potential of serum ITGB2-AS1 as a novel diagnostic biomarker and its correlation with ITGB2 expression and its ligand intercellular adhesion molecule-1 (ICAM-1), disease activity, and severity in RA and primary knee OA patients. SUBJECTS: Forty-three RA patients, 35 knee OA patients, and 22 healthy volunteers were included. RESULTS: Compared with healthy controls, serum ITGB2-AS1 expression was upregulated in RA patients but wasn't significantly altered in knee OA patients, whereas serum ICAM-1 protein levels were elevated in both diseases. ITGB2-AS1 showed discriminative potential for RA versus controls (AUC = 0.772), while ICAM-1 displayed diagnostic potential for both RA and knee OA versus controls (AUC = 0.804, 0.914, respectively) in receiver-operating characteristic analysis. In the multivariate analysis, serum ITGB2-AS1 and ICAM-1 were associated with the risk of developing RA, while only ICAM-1 was associated with the risk of developing knee OA. A panel combining ITGB2-AS1 and ICAM-1 showed profound diagnostic power for RA (AUC = 0.9, sensitivity = 86.05%, and specificity = 91.67%). Interestingly, serum ITGB2-AS1 positively correlated with disease activity (DAS28) in RA patients and with ITGB2 mRNA expression in both diseases, while ICAM-1 positively correlated with ITGB2 expression in knee OA patients. CONCLUSION: Our study portrays serum ITGB2-AS1 as a novel potential diagnostic biomarker of RA that correlates with disease activity. A predictive panel combining ITGB2-AS1 and ICAM-1 could have clinical utility in RA diagnosis. We also spotlight the association of ICAM-1 with knee OA diagnosis. The correlation of serum ITGB2-AS1 with ITGB2 expression in both diseases may be insightful for further mechanistic studies.