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Characterisation of Osteoprotegerin Autoantibodies in Coeliac Disease

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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.

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Acknowledgments

The authors would like to acknowledge the generous support of Coeliac UK/Core in funding this work.

Conflict of Interest

PLR, SHR and WDF have a patent application pending relating to the detection of osteoprotegerin antibodies in the diagnosis of osteoporosis. PLR reports Grants from ECTS and CSO during the conduct of the study; personal fees from IDS and a Grant from Menarini outside the submitted work. SHR reports Grants from Arthritis Research UK during the conduct of the study, consultancy fees from Merck and Novartis, Grants from Amgen and Eli Lilly and Company outside the submitted work. WDF reports fees from IDS, and Grants from Roche, Abbott, Siemens and Neotrix outside the submitted work. JS reports personal fees from Takeda, MSD and Shire outside the submitted work. NK reports Grants from Wellcome Trust outside the submitted work. All remaining authors have no disclosures.

Human and Animal Rights and Informed Consent

The study was approved by Lothian Research Ethics Committee, with all participants giving informed consent.

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Authors and Affiliations

  1. Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine (IGMM), Edinburgh, EH4 2XU, UK

    Ana Real, Barbara Hauser, Nick Kennedy, Jack Satsangi, Stuart H. Ralston & Philip L. Riches

  2. Human Genetics Unit, IGMM, Edinburgh, UK

    Nick Gilbert

  3. Gastroenterology Department, Lothian University Hospitals NHS Trust, Edinburgh, UK

    Alan Shand, Helen Gillett, Peter Gillett, Clive Goddard & Jack Satsangi

  4. Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Sevilla, Seville, Spain

    Carolina Sousa

  5. Biomedal SL, Seville, Spain

    Ángel Cebolla

  6. University of East Anglia, Norwich, UK

    William D. Fraser

Authors
  1. Ana Real
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  2. Nick Gilbert
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  3. Barbara Hauser
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  4. Nick Kennedy
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  5. Alan Shand
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  6. Helen Gillett
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  7. Peter Gillett
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  8. Clive Goddard
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  9. Ángel Cebolla
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  10. Carolina Sousa
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  11. William D. Fraser
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  12. Jack Satsangi
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  13. Stuart H. Ralston
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  14. Philip L. Riches
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Correspondence to Philip L. Riches.

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Real, A., Gilbert, N., Hauser, B. et al. Characterisation of Osteoprotegerin Autoantibodies in Coeliac Disease. Calcif Tissue Int 97, 125–133 (2015). https://doi.org/10.1007/s00223-015-0023-4

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  • DOI: https://doi.org/10.1007/s00223-015-0023-4

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