B cell epitopes on infliximab identified by oligopeptide microarray with unprocessed patient sera

Area of Science:

• Immunology
• Pharmacology
• Biotechnology

Background:

• Autoimmune diseases are treated with TNF-alpha-blocking antibodies like infliximab.
• Therapeutic antibodies can induce anti-drug antibodies, potentially reducing treatment effectiveness.

Purpose of the Study:

• To identify immunogenic epitopes on infliximab responsible for adverse effects.
• To understand the basis of anti-drug antibody induction for developing improved therapies.

Main Methods:

• Screening patient sera for anti-infliximab antibodies using ELISA.
• Analyzing high-titer sera on oligopeptide microarrays with infliximab sequences.
• Identifying immunogenic epitopes via infrared fluorescence scanning and comparative analysis.

Main Results:

• Six key epitopes on infliximab were identified, with four in the variable and two in the constant region.
• Three variable region epitopes are within the TNF-alpha binding site; a fourth is near it and contains a glycosylation site.
• No cross-reactivity was observed between anti-infliximab and anti-adalimumab antibodies in patient sera.

Conclusions:

• Characterizing immunogenic epitopes aids in developing less immunogenic therapeutic antibodies.
• Findings support informed decisions on switching infliximab therapy.
• Improved antibody design can reduce adverse events and prolong drug efficacy.