title: Characterisation of osteoprotegerin autoantibodies in coeliac disease.
abstract: Autoantibodies neutralising the effect of the bone regulatory cytokine osteoprotegerin (OPG) have been described in a patient with severe osteoporosis and coeliac disease. This study aimed to determine the prevalence and epitope specificity of autoantibodies to OPG in patients with coeliac disease, and correlate their presence with bone mineral density. A direct enzyme-linked immunosorbent assay was developed and used to screen patients with coeliac disease for autoantibodies to OPG. Recombinant fragments of OPG were made to evaluate the epitope specificity and affinity of these antibodies. Phenotype information of the patients was obtained by case note review. Raised titres of antibodies to OPG were found in 7/71 (9.8 %) patients with coeliac disease, compared with 1/72 (1.4 %) non-coeliac osteoporosis clinic control patients (p < 0.05). Our results suggest that a polyclonal antibody response to OPG is raised in these patients capable of recognising different epitopes of OPG with varying affinity. The titre of OPG antibodies was associated with lower bone mineral density Z-score of the hip in coeliac patients on univariate (p < 0.05) and multivariate analysis including age, sex height and weight as covariates (p < 0.01). Polyclonal antibodies to OPG are more common in patients with coeliac disease and are independently associated with lower bone mineral density Z-scores of the hip. Further work is required to establish the clinical utility of testing for OPG antibodies.
authors.affiliation: Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine (IGMM), Edinburgh, EH4 2XU, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Real
authors.forename: Nick
authors.initials: N
authors.lastname: Gilbert
authors.forename: Barbara
authors.initials: B
authors.lastname: Hauser
authors.forename: Nick
authors.initials: N
authors.lastname: Kennedy
authors.forename: Alan
authors.initials: A
authors.lastname: Shand
authors.forename: Helen
authors.initials: H
authors.lastname: Gillett
authors.forename: Peter
authors.initials: P
authors.lastname: Gillett
authors.forename: Clive
authors.initials: C
authors.lastname: Goddard
authors.forename: Ángel
authors.initials: Á
authors.lastname: Cebolla
authors.forename: Carolina
authors.initials: C
authors.lastname: Sousa
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.forename: Jack
authors.initials: J
authors.lastname: Satsangi
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.forename: Philip L
authors.initials: PL
authors.lastname: Riches
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015153:Blotting, Western; D015519:Bone Density / Q000502:physiology; D002446:Celiac Disease / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human