PT  - JOURNAL ARTICLE
AU  - Florence W L Tsui
AU  - Hing Wo Tsui
AU  - Facundo Las Heras
AU  - Kenneth P H Pritzker
AU  - Robert D Inman
TI  - Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spondylitis
AID  - 10.1136/annrheumdis-2013-203630
DP  - 2014 Oct 01
TA  - Annals of the Rheumatic Diseases
PG  - 1873--1879
VI  - 73
IP  - 10
4099  - http://ard.bmj.com/content/73/10/1873.short
4100  - http://ard.bmj.com/content/73/10/1873.full
SO  - Ann Rheum Dis2014 Oct 01; 73
AB  - 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 IgG 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.