Measuring adrenal autoantibody response: Interlaboratory concordance in the first international serum exchange for the determination of 21-hydroxylase autoantibodies ☆ Alberto Falorni a , ⁎ , 1 , Shu Chen b , 1 , Renato Zanchetta c , 1 , Liping Yu d , 1 , Claudio Tiberti e , 1 , Maria Luisa Bacosi a , 1 , Jadwiga Furmaniak b , 1 , Vittorio Bini a , 1 , Francesco Dotta f , 1 , George S. Eisenbarth d , 1 , Bernard Rees Smith b , 1 , Corrado Betterle c , 1 a Department of Internal Medicine, Section of Internal Medicine and Endocrine & Metabolic Sciences, University of Perugia, 06126 Perugia, Italy b FIRS Laboratories, RSR Ltd., Llanishen, Cardiff, CF14 5DU, UK c Endocrine Unit, Department of Medical and Surgical Sciences, University of Padua, 35122 Padua, Italy d Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA e Department of Clinical Sciences, Sapienza University, 00161 Rome, Italy f Department of Internal Medicine and Endocrine and Metabolic Sciences, University of Siena, 53100 Siena, Italy Received 21 March 2011; accepted with revision 21 April 2011 Available online 28 April 2011 KEYWORDS Adrenal insufficiency; Autoimmune Addison's disease; Autoimmune polyendocrine syndrome; Radioimmunoassay; Standardization Abstract 21-hydroxylase autoantibodies (21OHAb) are the gold standard immune marker to identify patients with clinical or subclinical autoimmune Addison's disease (AAD). No assessment of interlaboratory concordance has been made for 21OHAb measurement. Serum samples from 267 patients with primary adrenal insufficiency and from 83 healthy control subjects were distributed to four independent laboratories that determined presence and titer of 21OHAb, by using radiobinding assays with either in vitro translated 35 S-radiolabelled or 125 I-radiolabelled autoantigen. Cohen's κ of inter-rater agreement ranged from 0.857 to 0.983, showing a very good concordance of the positive/negative score among the four laboratories. Passing–Bablok regression showed a good agreement of 21OHAb titers arranged by ranks, but important discrepancies emerged at the Bland– Abbreviations 21OHAb, 21-hydroxylase autoantibodies; AAD, Autoimmune Addison's Disease; ACA, Adrenal Cortex Autoantibodies; AHC, adrenal hypoplasia congenita; ALD, adrenoleukodystrophy; APS, autoimmune polyendocrine syndrome; AUC, area under ROC curve; CI, confidence interval; IAN, Italian Addison Network; ICC, intra-class correlation coefficient; PAI, primary adrenal insufficiency; RC, repeatability coefficient; ROC, receiver-operating characteristic; TBC, tuberculosis; T1DM, type 1 diabetes mellitus. ☆ Disclosure statement: RSR Ltd is a manufacturer of medical diagnostics including kits for 21OH autoantibodies. ⁎ Corresponding author at: Department of Internal Medicine, Section of Internal Medicine and Endocrine & Metabolic Sciences, Via E. Dal Pozzo, 06126 Perugia, Italy. Fax: + 39 075 5730855. E-mail address: alberto.falorni@unipg.it (A. Falorni). 1 On behalf of the Italian Addison Network. 1521-6616/$ - see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.clim.2011.04.012 available at www.sciencedirect.com Clinical Immunology www.elsevier.com/locate/yclim Clinical Immunology (2011) 140, 291–299