P106 SIALIC ACID: A POSSIBLE ANTIGENIC EPITOPE IN THE GENERATION OF ANTIBODIES TO INFLIXIMAB (ATI). (18th January 2018)

• Record Type: Journal Article
• Authors: Zhang, Bing; Hwang, Caroline; Sheibani, Sarah; Tran-Minh, My-Linh; Allez, Mattieu; Shao, Ling
• Is Part Of: Inflammatory bowel diseases. Volume 24(2018)Supplement 1
• Page Start: S37
• Page End: S38
• Publication Date: 2018-01-18
• Subjects: Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1093/ibd/izy019.118
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract: ATIs develop in 8–60% of IBD patients1. Fully-humanized antibodies such as adalimumab and golimumab induce similar rates of immunogenicity, suggesting post-translational modifications as possible antigenic epitopes2. One consideration is sialylation, the addition of terminal N-acetylneuraminic acid (NANA) or N-glycolylneuraminic acid (NGNA) to N-linked glycosylations. Humans are unable to produce NGNA from the precursor NANA due to a single enzyme mutation3. Therefore, presence of NGNA on infliximab may induce ATI formation. Sera from 26 ATI-positive patients at Hopital Saint-Louis, Paris, were collected and centrifuged to obtain plasma. Infliximab was treated with either PNGase F, which removes all N-linked glycosylations, or with neuraminidase, which removes only the terminal NANA or NGNA. Enzyme-linked immunosorbent assay (ELISA) was performed with each patient's plasma to detect antibodies against untreated (UI), PNGase F-treated (PI), and neuraminidase-treated (NI) infliximab. Wilcoxon signed-rank test was used to compare absorbance between UI with PI and NI. NF-κB luciferase reporter assay using 293T cells was performed to measure the potency of untreated and treated infliximab. After incubating with patient plasma, no difference in ATI binding was detected between PI and UI (p=0.9191). Significant decrease in ATI was detected in NI compared to UI (p=0.0215) (Fig. 1). Treating infliximab with PNGase F lowered ATI binding in 54% (14/26) of samples; treatment with neuraminidase lowered ATI binding in 69% (18/26) of samples. Evaluation of UI, PI and NI revealed no significant difference in potency (p=0.9) (Fig. 2). Selective removal of terminal sialic acid from infliximab decreases the binding of antibodies to infliximab in ATI-positive patients. In vitro, this modification does not diminish the ability of infliximab to target TNFα. 1. Am J Gastroenterol. 2013;108(1):40–7. 2. Ann Rheum Dis. 2015;74(8):e40. 3. Glycobiology. 2008;18(10):818–30.