Characterisation of osteoprotegerin autoantibodies in coeliac disease

Ana Real, Nick Gilbert, Barbara Hauser, Nick Kennedy, Alan Shand, Helen Gillett, Peter Gillett, Clive Goddard, Ángel Cebolla, Carolina Sousa, William Fraser, Jack Satsangi, Stuart Ralston, Philip Riches (Lead Author)

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Abstract

Objectives
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.

Methods
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.

Results
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 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).

Conclusion
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.
Original languageEnglish
Pages (from-to)125-133
JournalCalcified Tissue International
Volume97
Issue number2
Early online date20 Jun 2015
DOIs
Publication statusPublished - Aug 2015

Keywords

  • Osteoporosis
  • Coeliac disease
  • Osteoprotegerin
  • Autoantibodies

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