AUTHOR=Capecchi Riccardo , Migliorini Paola , Zanzi Federico , Maltinti Simona , Puxeddu Ilaria , de Bortoli Nicola , Bellini Massimo , Costa Francesco , Marchi Santino , Bertani Lorenzo 

TITLE=Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.654319

DOI=10.3389/fphar.2021.654319

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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- &lt;2) and mucosal healing (Mayo Endoscopic Score &lt;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.</p><p><bold>Results:</bold> 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 (<italic>p</italic> = 0.04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (<italic>p</italic> = 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 (<italic>p</italic> &lt; 0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (<italic>r</italic><sup>2</sup> = 0,2211; <italic>p</italic> = 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 (<italic>p</italic> = 0,0135 and <italic>p</italic> = 0,0089, respectively).</p><p><bold>Conclusion:</bold> 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.</p>