Screening of endocrine organ-specific humoral autoimmunity in 47,XXY Klinefelter’s syndrome reveals a significant increase in diabetes-specific immunoreactivity in comparison with healthy control men
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The aim of this study was to evaluate the frequency of humoral endocrine organ-specific autoimmunity in 47,XXY Klinefelter’s syndrome (KS) by investigating the autoantibody profile specific to type 1 diabetes (T1DM), Addison’s disease (AD), Hashimoto thyroiditis (HT), and autoimmune chronic atrophic gastritis (AG). Sixty-one adult Caucasian 47,XXY KS patients were tested for autoantibodies specific to T1DM (Insulin Abs, GAD Abs, IA-2 Abs, Znt8 Abs), HT (TPO Abs), AD (21-OH Abs), and AG (APC Abs). Thirty-five of these patients were not undergoing testosterone replacement therapy TRT (Group 1) and the remaining 26 patients started TRT before the beginning of the study (Group 2). KS autoantibody frequencies were compared to those found in 122 control men. Six of 61 KS patients (9.8 %) were positive for at least one endocrine autoantibody, compared to 6.5 % of controls. Interestingly, KS endocrine immunoreactivity was directed primarily against diabetes-specific autoantigens (8.2 %), with a significantly higher frequency than in controls (p = 0.016). Two KS patients (3.3 %) were TPO Ab positive, whereas no patients were positive for AD- and AG-related autoantigens. The autoantibody endocrine profile of untreated and treated KS patients was not significantly different. Our findings demonstrate for the first time that endocrine humoral immunoreactivity is not rare in KS patients and that it is more frequently directed against type 1 diabetes-related autoantigens, thus suggesting the importance of screening for organ-specific autoimmunity in clinical practice. Follow-up studies are needed to establish if autoantibody-positive KS patients will develop clinical T1DM.
KeywordsKlinefelter’s syndrome Type 1 diabetes Hypogonadism Autoimmunity
The study was funded by the Italian Ministry of Health and the Italian Medicines Agency (AIFA): research project MRAR08Q009 on rare diseases. Author’s contribution: F.P. contributed to data collection, statistical analysis, data interpretation, wrote the manuscript; C.T. contributed to data interpretation and revised the manuscript; G.S., A.A., and A.S. contributed to data collection; L.A. and G.D. revised the manuscript; R.A. is the guarantor of this work and, as such, had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Thanks to Marie-Hélène Hayles for the language revision.
Conflict of interest
No potential conflicts of interest relevant to this article were reported.
- 14.A.P. Weetman, Chronic autoimmune thyroiditis, in Werner and Ingbar’s the thyroid: a fundamental and clinical text, 8th edn., ed. by L.E. Braverman, R.D. Utiger (Lippincott Williams & Wilkins, Philadelphia, 2000), pp. 721–732Google Scholar
- 22.V. Lampasona, M. Schlosser, P.W. Mueller, A.J.K. Williams, J.M. Wenzlau, J.C. Hutton, P. Achenbach, Participating Laboratories, Diabetes antibody standardization program: first proficiency evaluation of assays for autoantibodies to zinc transporter 8. Clin. Chem. 57(12), 1693–1702 (2011)CrossRefPubMedGoogle Scholar
- 25.S. Whittingham, I.R. Mackay, Pernicious anemia and gastric atrophy, in The Autoimmune Diseases, ed. by N.R. Rose, I.R. Mackay (Academic Press, New York, 1985), pp. 243–266Google Scholar
- 26.M. Jang-Feng, X. Hong-Li, W. Xue—Yan et al., Prevalence and risk factors of diabetes in patients with Klinefelter syndrome: a longitudinal study. Reprod. Endocrinol. 98, 1331–1335 (2012)Google Scholar
- 27.A. Bojesen, K. Kristensen, N.H. Birkebaek, J. Fedder, L. Mosekilde, P. Bennett, P. Laurberg, J. Frystyk, A. Flyvbjerg, J.S. Christiansen, C.H. Gravolt, The metabolic syndrome Is frequent in Klinefelter’s syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care 29, 1591–1598 (2006)CrossRefPubMedGoogle Scholar
- 29.A.L. Notkins, A. Lernmark, Autoimmune type 1 diabetes: resolved and unresolved issues. J. Clin. Invest. 108(12), 47–52 (2001)Google Scholar
- 32.L.I. Alves, E. Davini, M.R. Correia, R.T. Fukui, R.F. Santos, M.R. Cunha, D.M. Rocha, W.M.G. Volpini, M.E.R. Silva, Autoantibodies and high-risk HLA susceptibility markers in first-degree relatives of Brazilian patients with type 1 diabetes mellitus: a progression to disease based study. J. Clin. Immunol. 32, 778–785 (2012)CrossRefPubMedGoogle Scholar
- 39.J. Nielsen, K. Johansen, H. Yde, Frequency of diabetes mellitus in patients with Klinefelter’s syndrome of different chromosome constitutions and the XYY syndrome. Plasma insulin and growth hormone level after a glucose load. J. Clin. Endocrinol. Metab. 29, 1062–1073 (1969)CrossRefPubMedGoogle Scholar