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P456 Ig glycosylation in ulcerative colitis: it's time for new biomarkers

Capecchi, R.(1);Migliorini, P.(1);Zanzi, F.(1);Maltinti, S.(1);Puxeddu, I.(1);De Bortoli, N.(1);Bellini, M.(1);Costa, F.(2);Marchi, S.(1);Bertani, L.(1);

(1)University of Pisa, Translational Research and New Technologies in Medicine and Surgery, Pisa, Italy;(2)Pisa University Hospital, General Surgery and Gastroenterology - IBD Unit, Pisa, Italy

Background

Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome.

Methods

We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- <2) and mucosal healing (Mayo Endoscopic Score <2). On serum samples collected at baseline and after 54 weeks of treatment, a Lectin-based ELISA assay was performed, and specific glycosylation patterns were evaluated by biotin-labelled lectins. We have also collected 21 healthy controls (NHS) samples, age and sex-matched.

Results

Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p=0,04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p=0,04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p<0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (r2= 0,2211; p=0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients (p= 0,0135 and p=0,0089 , respectively).

Conclusion

Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.

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