Title : Serum levels of novel
noggin and
sclerostin-immune complexes are elevated in ankylosing spondylitis
Abstract :
- BACKGROUND: 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 (IC) composed of IgG autoantibodies to NOG and SOST were detected by immunoprecipitation and Western blot analyses
- Epitope-specific Ig G were measured using peptide-binding ELISA
- 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 IC 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 IC are present in AS sera (p<0.001)
- We showed 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 IgG recognising the NOG- N54 and SOST-S146 peptides compared to the levels in normal controls, IBD and MBP patients (one way analysis of variance p<0.0001)
- CONCLUSIONS: This is the first report showing IgG autoantibodies to NOG and SOST in normal individuals, and higher levels of NOG and/or SOST- IgG IC probably contribute to neo-ossification in AS patients
- These novel findings hold the promise of earlier diagnosis, better management of AS with comorbidities and new therapeutic approaches to modulate ankylosis in AS