Frontiers in medicine · 2026
Circulating microRNAs as biomarkers of disease activity and treatment response in Crohn's disease patients receiving infliximab or vedolizumab: a longitudinal cohort study.
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Bertin Luisa, Giraldi Lara, Cavagna Camilla, Caranfil Cristina, Barberio Brigida, Cardin Romilda, Facchin Sonia, Carlotto Chiara, Minotto Milena, Savarino Edoardo Vincenzo, Zingone Fabiana
Аннотация
BACKGROUND AND AIMS: Validated biomarkers of biologic response in Crohn's disease (CD) are lacking. We assessed whether serum microRNAs (miRNAs) track disease activity and predict outcomes during biologic induction in CD.
METHODS: Thirty-nine adults with active CD initiating infliximab (n = 20) or vedolizumab (n = 19) and 10 controls were studied at a single centre. Serum was sampled at the first and fourth infusions. Six target miRNAs were qPCR-quantified and normalised to the geometric mean of miR-93-5p and miR-425-5p. Harvey-Bradshaw Index, C-reactive protein, faecal calprotectin and Simple Endoscopic Score for CD were recorded at baseline, post-induction and 12 months. Four pre-specified analysis families were tested with false discovery rate (FDR) correction for multiple testing. This was a single-centre, exploratory, hypothesis-generating study.
RESULTS: miR-21-5p and miR-146b-5p were significantly reduced in CD versus controls (q < 0.05). Baseline miR-146b-5p inversely predicted post-induction CRP independently of baseline disease severity (partial r = -0.46, p = 0.010), supporting it as a candidate severity-independent predictor of biochemical response. Post-induction miR-424-5p strongly tracked concurrent inflammation (faecal calprotectin: Spearman ρ = +0.52, q = 0.004; CRP: ρ = +0.44, q = 0.030), these associations remained significant after adjustment for baseline disease severity, after leave-one-out removal of single patients, and under single-reference normalisation. An exploratory post-hoc analysis linked treatment-induced miR-106a-5p upregulation to penetrating (Montreal B3) disease (permutation p = 0.019).
CONCLUSION: Serum miRNAs offer novel predictive (baseline miR-146b-5p and miR-106a-5p) and concurrent (post-induction miR-424-5p) biomarker signals during biologic induction in CD, providing information complementary to faecal calprotectin. Prospective independent validation is warranted before clinical translation.
METHODS: Thirty-nine adults with active CD initiating infliximab (n = 20) or vedolizumab (n = 19) and 10 controls were studied at a single centre. Serum was sampled at the first and fourth infusions. Six target miRNAs were qPCR-quantified and normalised to the geometric mean of miR-93-5p and miR-425-5p. Harvey-Bradshaw Index, C-reactive protein, faecal calprotectin and Simple Endoscopic Score for CD were recorded at baseline, post-induction and 12 months. Four pre-specified analysis families were tested with false discovery rate (FDR) correction for multiple testing. This was a single-centre, exploratory, hypothesis-generating study.
RESULTS: miR-21-5p and miR-146b-5p were significantly reduced in CD versus controls (q < 0.05). Baseline miR-146b-5p inversely predicted post-induction CRP independently of baseline disease severity (partial r = -0.46, p = 0.010), supporting it as a candidate severity-independent predictor of biochemical response. Post-induction miR-424-5p strongly tracked concurrent inflammation (faecal calprotectin: Spearman ρ = +0.52, q = 0.004; CRP: ρ = +0.44, q = 0.030), these associations remained significant after adjustment for baseline disease severity, after leave-one-out removal of single patients, and under single-reference normalisation. An exploratory post-hoc analysis linked treatment-induced miR-106a-5p upregulation to penetrating (Montreal B3) disease (permutation p = 0.019).
CONCLUSION: Serum miRNAs offer novel predictive (baseline miR-146b-5p and miR-106a-5p) and concurrent (post-induction miR-424-5p) biomarker signals during biologic induction in CD, providing information complementary to faecal calprotectin. Prospective independent validation is warranted before clinical translation.