MicroRNA and granulocyte-monocyte adsorption apheresis combotherapy after inadequate response to anti-TNF agents in ulcerative colitis

Abstract

Background

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, affecting millions of individuals throughout the world, and producing an impaired health-related quality of life. Granulocyte and monocyte apheresis (GMA) is a therapeutic option for UC management to induce remission by selective removal of activated leukocytes from bloodstream. Despite the knowledge of the important role of epigenetics in UC pathogenesis, and in the response to different treatments, nothing is known about the role of microRNAs in GMA therapy in UC patients.

Methods

Seven consecutively UC patients who started GMA in combo therapy with infliximab were recruited. Peripheral blood samples were taken before the apheresis session, at the start of the induction (S0) and at the end (S10). They were follow-up during the induction phase (10 sessions: 2 sessions for a week during 3 wk and 1 session for a week during 4 wk) of the treatment at a tertiary hospital (Hospital la Fe) and 6 mo after finishing the GMA induction therapy. MiRNA was extracted and analyzed by RT-PCR. R software and GraphPad were used.

Results

Clinical disease activity significantly decreased after induction therapy with GMA (median partial Mayo score 2 (IQR, 1-6) (P < .05). Fecal calprotectin value and CRP value significantly decreased after induction therapy. Five microRNAs modified their expression during GMA (unsupervised analysis): miR-342-3p, miR-215-5p, miR-376c-3p, miR-139-5p, and miR-150-5p. When a sub-analysis was performed in those patients who showed good response to apheresis treatment (n = 5), two microRNAs showed to be implicated: miR-215-5p and miR-365a-3p. These are preliminary but promising and novel results, as it is the first time, to our knowledge that microRNA profiles have been studied in the context of GMA treatment for IBD.