Non-genetic biomarkers for ankylosing spondylitis: An umbrella review

Abstract

Objective: The objective of the study was to provide an overview of the existing evidence on non-genetic biomarkers for ankylosing spondylitis (AS).

Methods: In this umbrella review, we searched PubMed and Web of Science from database inception to October 31, 2020. Systematic reviews and meta-analyses of observational studies investigating the associations between any non-genetic biomarkers and AS were included. We estimated summary standardized mean difference (SMD) along with 95% confidence interval (CI), I² statistic, 95% prediction interval (PI), and assessed small-study effects and excess significance bias. The study was registered in PROSPERO with registration number of CRD42020218240.

Results: A total of 1276 publications were identified, of which 21 articles covering 43 non-genetic biomarkers were eligible for inclusion. Evidence of 22 (51%) non-genetic biomarkers exhibited a nominally significant effect (p < 0.05) on AS, and 7 associations (14%) showed small-study effects. The associations of platelet count (SMD: 0.53, 95% CI: 0.36 to 0.71) and serum interleukin (IL)-23 levels (SMD = 2.03, 95% CI: 1.27 to 2.79) with AS presented highly suggestive evidence, while circulating IL-17 levels (SMD = 2.36, 95% CI: 1.71, 3.01) and Treg/PBMC ratio (SMD = -0.75, 95% CI: -1.06 to -0.44) presented suggestive evidence. However, these associations showed large or very large between-study heterogeneity, suggesting an indefinite direction for the effect when 95% PIs were considered.

Conclusion: No convincing evidence supported the existence of a non-genetic biomarker for AS. Some highly suggestive associations might be affected by bias, therefore, promising non-genetic biomarkers for AS remain limited at least based on the current evidence from observational studies.

Keywords: ankylosing spondylitis; biomarker; meta-analysis; systematic review; umbrella review.