Background/Purpose: Unravelling the basis of joint inflammation and ankylosis represents a major challenge in ankylosing spondylitis (AS) research. As noggin (NOG) and sclerostin (SOST) have recently been associated with the disease process in mouse and human studies respectively, we explored the immune responses to these two molecules in AS.

Methods: Immune-complexes (ICs) comprised of IgG autoantibodies to NOG and SOST were detected by immunoprecipitation and Western blot analyses. Epitope-specific IgGs were measured using peptide-binding ELISAs. Serum samples were obtained from healthy controls and patients with AS, mechanical back pain (MBP) and inflammatory bowel disease (IBD) with or without concomitant AS.

Results: NOG- and SOST-IgG ICs were present in NOG-treated and untreated ank/ank (progressive ankylosis), but not in wild-type mice. Higher than normal levels of NOG- and SOST-IgG ICs are present in AS sera (p<0.001). We showed that a SOST peptide (SOST-S146, with homology to a bacterial glycotransferase peptide) binds to a NOG peptide (NOG-N54) which contains a N-glycosylation site. AS patients have higher levels of IgGs recognizing the NOG-N54 and SOST-S146 peptides compared to the levels in normal controls, IBD and MBP patients (1 way ANOVA: p<0.0001).

Conclusion: This is the first report showing IgG autoantibodies to NOG and SOST in normal individuals and higher levels of NOG- and/or SOST-IgG ICs likely contribute to neo-ossification in AS patients. These novel findings implicate earlier diagnosis, better management of AS with comorbidities and new therapeutic approaches to modulate ankylosis in AS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-levels-of-novel-noggin-and-sclerostin-immune-complexes-are-elevated-in-ankylosing-spondylitis/