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

Abstract

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.

Glycans as a key factor in self and nonself discrimination: impact on the breach of immune tolerance

“…MGAT5 genetic variants were described to influence plasma IgG glycome composition in UC patients, particularly with agalactosylation of IgGs Fc, correlated with a pro‐inflammatory phenotype [132]. Moreover, the Fc N ‐glycosylation profile of IgGs, particularly lower IgG galactosylation levels, were associated with IBD clinical features, such as more extensive and progressive disease [158] and with clinical and endoscopic activity in UC patients [159]. Treatment with biologics, such as anti‐TNF therapy was described to increase IgG Fc galactosylation [159].…”

“…Moreover, the Fc N ‐glycosylation profile of IgGs, particularly lower IgG galactosylation levels, were associated with IBD clinical features, such as more extensive and progressive disease [158] and with clinical and endoscopic activity in UC patients [159]. Treatment with biologics, such as anti‐TNF therapy was described to increase IgG Fc galactosylation [159]. IgG Fc glycosylation profile was found to be able to discriminate between UC, CD and healthy controls [158,160].…”

Predictive, preventive and personalised approach as a conceptual and technological innovation in primary and secondary care of inflammatory bowel disease benefiting affected individuals and populations

“…Low mucosal IL23 expression at baseline relates to UST treatment resistance [33]. Glycosylation experiments performed in the serum of patients with UC revealed that certain glycan structures exposed in the immunoglobulins might predict the response to infliximab (IFX) or ADA [34]. Similarly, the classification of IBD patients according to their basal circulating levels of nicotinamide phosphoribosyltransferase (NAMPT) discriminates with high sensitivity and specificity for the patients that will benefit from ADA treatment [35].…”