Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spondylitis.
Ann Rheum Dis
; 73(10): 1873-9, 2014 Oct.
Article
en En
| MEDLINE
| ID: mdl-23894062
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 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.Palabras clave
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Banco de datos:
MEDLINE
Asunto principal:
Espondilitis Anquilosante
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Proteínas Portadoras
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Marcadores Genéticos
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Proteínas Morfogenéticas Óseas
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Complejo Antígeno-Anticuerpo
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Risk_factors_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article