Stabilized Cyclic Peptides as Scavengers of Autoantibodies:
Neutralization of Anticitrullinated Protein/Peptide Antibodies in
Rheumatoid Arthritis
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Abstract
The
occurrence of autoantibodies is a hallmark of rheumatoid arthritis,
specifically those autoantibodies targeting proteins containing the
arginine-derived amino acid citrulline. There is strong evidence showing
that the occurrence of anticitrullinated protein/peptide antibodies
(ACPA) are involved in disease progression, and ACPA was recently
shown to induce pain in animals. Here, we explore a novel concept
useful for research, diagnostics, and possibly therapy of autoimmune
diseases, namely, to directly target and neutralize autoantibodies
using peptide binders. A high-affinity peptide-based scavenger of
ACPA was developed by grafting a citrullinated epitope derived from
human fibrinogen into a naturally occurring stable peptide scaffold.
The best scavenger comprises the truncated epitope α-fibrinogen,
[Cit573]fib(566–580), grafted into the scaffold sunflower trypsin
inhibitor-1, SFTI-1. The final peptide demonstrates low nanomolar
apparent affinity and superior stability