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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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IMPACT FACTOR 2017: 3.556

CiteScore 2017: 2.34

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1437-4331
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Volume 56, Issue 6

Issues

A new ELISA for autoantibodies to steroid 21-hydroxylase

Maria del Pilar Larosa / Shu Chen / Nora Steinmaus / Hannah Macrae / Liang Guo / Stefano Masiero
  • Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy
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/ Silvia Garelli
  • Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy
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/ Miriam Dalla Costa
  • Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy
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/ Artur Bossowski
  • Department of Pediatrics, Endocrinology and Diabetes with a Cardiology Unit, Medical University in Bialystok, Bialystok, Poland
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/ Jadwiga Furmaniak / Corrado Betterle
  • Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy
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/ Bernard Rees Smith
Published Online: 2017-12-21 | DOI: https://doi.org/10.1515/cclm-2017-0456

Abstract

Background:

A new ELISA for autoantibodies to steroid 21-hydroxylase (21-OH Ab) is described.

Methods:

In the assay test sample autoantibodies form a bridge between 21-OH coated onto the plate well and liquid phase 21-OH-biotin. Bound 21-OH-biotin is detected by the addition of streptavidin peroxidase and colorogenic peroxidase substrate.

Results:

Of 100 samples from patients with autoimmune Addison’s disease, 86 (86%) were positive for 21-OH Ab ELISA whereas 84 (84%) were positive in an immunoprecipitation assay based on 125I-labeled 21-OH. Six (0.6%) of 928 healthy adult blood donors and 1 (2.0%) of 49 adult patients with type 1 diabetes mellitus (T1DM) were positive by ELISA. No samples from adult patients with Graves’ disease (GD; n=50), celiac disease (n=29), systemic lupus erythematosis (n=9) or rheumatoid arthritis (n=20) were positive by ELISA. However, 2/51 (3.9%) children with GD, 3/69 (4.3%) children with Hashimoto’s thyroiditis (HT) and 3/119 (2.5%) children with T1DM alone or associated with autoimmune thyroid disorders were ELISA positive.

Conclusions:

The new assay should be useful for screening patients known to be at increased risk of developing clinical autoimmune Addison’s disease, in particular children with HT, GD and/or T1DM.

Keywords: autoantibodies; autoimmune Addison’s disease; autoimmune adrenalitis; disease prediction; ELISA; population screening; steroid 21-hydroxylase

References

  • 1.

    Betterle C, Zanchetta R. Adrenalitis. In: Rose NR, Mackay IR, editors. The autoimmune diseases. London, UK: Elsevier Academic Press, 2006:501–14.Google Scholar

  • 2.

    Betterle C, Zanchetta R, Presotto F. Addison disease. In: Weetman AP, editor. Autoimmune diseases in endocrinology ISBN 978-1-58829-733-4. New York, USA: Humana Press, 2008:303–29.Google Scholar

  • 3.

    Betterle C, Garelli S, Presotto F, Furmaniak J. From appearance of adrenal autoantibodies to clinical symptoms of Addison’s disease: natural history. In: Arvat E, Falorni A, editors. Cortisol excess and insufficiency hormone research, Vol. 46 (DOI: 10.1159/000443872). Basel, Switzerland: Karger, 2016:133–45.Google Scholar

  • 4.

    Neufeld M, Blizzard RM. Polyglandular autoimmune disease. In: Pinchera A, Doniach D, Fenzi GF, Baschieri L, editors. Symposium on autoimmune aspects of endocrine disorders. New York: Academic Press, 1980:357–65.Google Scholar

  • 5.

    Betterle C. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev 2002;23:327–64.CrossrefPubMedGoogle Scholar

  • 6.

    Husebye ES, Perheentupa J, Rautemaa R, Kämpe O. Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I. J Intern Med 2009;265:514–29.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 7.

    Coles J, Betterle C, Volpato M, Prentice L, Rees Smith B, Furmaniak J. Immunoprecipitation assay for autoantibodies to steroid 21-hydroxylase in autoimmune adrenal diseases. Clin Chem 1995;41:375–80.PubMedGoogle Scholar

  • 8.

    Tanaka H, Perez MS, Powell M, Sanders JF, Sawicka J, Chen S, et al. Steroid 21-hydroxylase autoantibodies: measurements with a new immunoprecipitation assay. J Clin Endocrinol Metab 1997;82:1440–6.PubMedGoogle Scholar

  • 9.

    Betterle C, Volpato M, Pedini B, Chen S, Rees Smith B, Furmaniak J. Adrenal-cortex autoantibodies (ACA) and steroid- producing cells autoantibodies (StCA) in patients with Addison’s disease: comparison between immunofluorescence and immunoprecipitation assays. J Clin Endocrinol Metab 1999;84:618–22.Google Scholar

  • 10.

    Betterle C, Coco G, Zanchetta R. Adrenal cortex autoantibodies in subjects with normal adrenal function. Best Pract Res Clin Endocrinol Metab 2005;19:85–99.CrossrefPubMedGoogle Scholar

  • 11.

    Betterle C, Scarpa R, Garelli S, Morling L, Lazzarotto F, Presotto F, et al. Addison’s disease: a survey on 633 patients in Padova. Eur J Endocrinol 2013;169:773–84.Web of SciencePubMedCrossrefGoogle Scholar

  • 12.

    Betterle C, Scalici C, Presotto F, Pedini B, Moro L, Rigon F, et al. The natural history of adrenal function in autoimmune patients with adrenal autoantibodies. J Endocrinol 1988;117:467–75.CrossrefPubMedGoogle Scholar

  • 13.

    Betterle C, Volpato M, Rees Smith B, Furmaniak J, Chen S, Greggio NA, et al. I Adrenal cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of high progression to clinical Addison’s disease. J Clin Endocrinol Metab 1997;82:932–8.PubMedGoogle Scholar

  • 14.

    Betterle C, Volpato M, Rees Smith B, Furmaniak J, Chen S, Zanchetta R, et al. II Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases: markers of high progression to clinical Addison’s disease. J Clin Endocrinol Metab 1997;82:939–42.PubMedGoogle Scholar

  • 15.

    Coco G, Dal Pra C, Presotto F, Albergoni MP, Canova C, Pedini B, et al. Estimated risk for developing autoimmune Addison’s disease in patients with adrenal cortex antibodies. J Clin Endocrinol Metab 2006;91:1637–45.PubMedCrossrefGoogle Scholar

  • 16.

    Triolo TM, Armstrong TK, McFann K, Yu L, Rewers MJ, Klingensmith GJ, et al. Additional autoimmune disease found in 33% of patients at type 1 diabetes onset. Diabetes Care 2011;34:1211–3.Web of ScienceCrossrefPubMedGoogle Scholar

  • 17.

    Burbelo PD, Lebovitz EE, Bren KE, Bayat A, Paviol S, Wenzlau JM, et al. Extrapancreatic autoantibody profiles in type 1 diabetes. PLoS One 2012;7:e45216.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 18.

    Kordonouri O, Hartmann R, Deiss D, Wilms M, Grüters-Kieslich A. Natural course of autoimmune thyroiditis in type 1 diabetes: association with gender, age, diabetes duration, and puberty. Arch Dis Child 2015;90:411–4.Google Scholar

  • 19.

    Głowińska-Olszewska B, Michalak J, Łuczyński W, Larosa M, Chen S, Furmaniak J, et al. Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes. J Pediatr Endocrinol Metab 2016;29:647–56.Web of SciencePubMedGoogle Scholar

  • 20.

    Falorni A, Chen S, Zanchetta R, Yu L, Tiberti C, Bacosi ML, et al. Measuring adrenal antibody response: interlaboratory concordance in the first international serum exchange for the determination of 21-hydroxylase autoantibodies. Clin Immunol 2011;140:291–9.PubMedCrossrefGoogle Scholar

  • 21.

    Falorni A, Bini V, Betterle C, Brozzetti A, Castaño L, Fichna M, et al. Determination of 21-hydroxylase autoantibodies: inter-laboratory concordance in the Euradrenal International Serum Exchange Program. Clin Chem Lab Med 2015;53:1761–70.PubMedWeb of ScienceGoogle Scholar

  • 22.

    Coutinho A, Kazatchkine MD, Avrameas S. Natural autoantibodies. Curr Opin Immunol 1995;7:812–8.CrossrefPubMedGoogle Scholar

  • 23.

    Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol 2010;125:S41–52.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 24.

    Barker JM, Ide A, Hostetler C, Yu L, Miao D, Fain PR, et al. Endocrine and immunogenetic testing in individuals with type 1 diabetes and 21-hydroxylase autoantibodies: Addison’s disease in a high risk population. J Clin Endocrinol Metab 2004;90:128–34.Google Scholar

  • 25.

    Betterle C, Morlin L. Autoimmune Addison’s disease. Endocr Dev 2011;20:161–72.CrossrefPubMedGoogle Scholar

  • 26.

    Cooper GS, Bynum ML, Somers EC. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun 2009;33:197–207.Web of SciencePubMedCrossrefGoogle Scholar

About the article

Corresponding author: Dr. Bernard Rees Smith, FIRS Laboratories, RSR Ltd., Parc Ty Glas, Llanishen, Cardiff, CF14 5DU, UK


Received: 2017-05-24

Accepted: 2017-11-06

Published Online: 2017-12-21

Published in Print: 2018-05-24


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: The work was funded by RSR Limited, Cardiff, UK.

Employment or leadership: MdPL, SC, NS, HM, LG, JF and BRS are employees of RSR Limited. RSR Ltd. is a developer of medical diagnostics, including kits for measuring 21-OH antibodies.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 6, Pages 933–938, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0456.

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