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

详细信息    查看全文

• 作者：Francesca Panimolle ; Claudio Tiberti ; Simona Granato ; Antonella Semeraro…
• 关键词：Klinefelter’s syndrome ; Type 1 diabetes ; Hypogonadism ; Autoimmunity
• 刊名：Endocrine
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：52
• 期：1
• 页码：157-164
• 全文大小：550 KB
• 参考文献：1.F. Lanfranco, A. Kamischke, M. Zitzmann et al., Klinefelter’s syndrome. Lancet 364, 273–283 (2004)CrossRef PubMed
  2.A.F. Radicioni, E. De Marco, D. Gianfrilli et al., Strategies and advantages of early diagnosis in Klinefelter’s syndrome. Mol. Hum. Reprod. 6, 434–440 (2010)CrossRef
  3.A. Bojesen, S. Juul, N.H. Bikebaek et al., Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses. J. Clin. Endocrinol. Metab. 88, 622–626 (2006)CrossRef
  4.A.H. Sawalha, J.B. Harley, R. Hal Scofield, Autoimmunity and Klinefelter’s syndrome: when men have two X chromosomes. J. Autoimmun. 33(1), 31–34 (2009)CrossRef PubMed PubMedCentral
  5.L.A. Abramowitz, S. Olivier-Van Stichelen, J.A. Hanover, Chromosome imbalance as a driver of sex disparity in disease. J. Genomics 2, 77–88 (2014)CrossRef PubMed PubMedCentral
  6.M. Cutolo, A. Sulli, S. Capellino et al., Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. Lupus 13(9), 653–658 (2004)CrossRef
  7.N.J. Olsen, W.J. Kovacs, Gonadal steroids and immunity. Endocr. Rev. 17, 369–384 (1996)PubMed
  8.C. Oktenli, Z. Yesilova, I.H. Kocar et al., Study of autoimmunity in Klinefelter’s syndrome and idiopathic hypogonadotropic hypogonadism. J. Clin. Immuno. 22, 137–143 (2002)CrossRef
  9.A.M.B. Bjørn, A. Bojesen, C.H. Gravholt, P. Laurberg, Hypothyroidism secondary to hypothalamic-pituitary dysfunction may be part of the phenotype in klinefelter syndrome: a case-control study. J. Clin. Endocrinol. Metab. 94(7), 2478–2481 (2006)CrossRef
  10.G.S. Eisenbarth, Update in type 1 diabetes. J. Clin. Endocrinol. Metab. 92, 2403–2417 (2007)CrossRef PubMed
  11.M. Knip, H. Siljander, Autoimmune mechanisms in type 1 diabetes. Autoimmun. Rev. 7, 550–557 (2008)CrossRef PubMed
  12.O. Winqvist, F.A. Karlsson, O. Kämpe, 21-Hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet 339(8809), 1559–1562 (1992)CrossRef PubMed
  13.J. Bednarek, J. Furmaniak, N. Wedlock et al., Steroid 21-hydroxylase is a major autoantigen involved in adult onset autoimmune Addison’s disease. FEBS Lett. 309(1), 51–55 (1992)CrossRef PubMed
  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. 721–732
  15.R.G. Strickland, I. Mackay, A reappraisal of the nature and significance of chronic atrophic gastritis. Am. J. Dig. Dis. 18, 426–440 (1973)CrossRef PubMed
  16.C. Tiberti, L. Yu, F. Lucantoni et al., Detection of four diabetes specific autoantibodies in a single radioimmunoassay: an innovative high-throughput approach for autoimmune diabetes screening. Clin. Exp. Immunol. 166(3), 317–324 (2011)CrossRef PubMed PubMedCentral
  17.P. Vardi, S.A. Dib, M. Tuttleman et al., Competitive insulin autoantibody RIA: prospective evaluation of subjects at high risk for development of Type 1 diabetes mellitus. Diabetes 36, 1286–1291 (1987)CrossRef PubMed
  18.C.E. Grubin, T. Daniels, B. Toivola et al., A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM. Diabetologia 37, 344–350 (1994)CrossRef PubMed
  19.C. Törn, P.W. Mueller, M. Schlosser et al., Diabetes antibody standardization program: evaluation of assays for autoantibodies to glutamic acid decarboxylase and islet antigen-2. Diabetologia 51, 846–852 (2008)CrossRef PubMed
  20.C. Tiberti, A. Verrienti, B. Fiore et al., IA-2 combined epitope assay: a new, highly sensitive approach to evaluate IA-2 humoral autoimmunity in type 1 diabetes. Clin. Immunol. 115, 260–267 (2005)CrossRef PubMed
  21.J.M. Wenzlau, K. Juhl, L. Yu et al., The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc. Natl. Acad. Sci. USA. 104, 17040–17045 (2007)CrossRef PubMed PubMedCentral
  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)CrossRef PubMed
  23.A. Falorni, S. Chen, R. Zanchetta et al., Measuring adrenal autoantibody response: Interlaboratory concordance in the first international serum exchange for the determination of 21-hydroxylase autoantibodies. Clin. Immunol. 140, 291–299 (2011)CrossRef PubMed
  24.G. Huber, J.J. Staub, C. Meier et al., Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J. Clin. Endocrinol. Metab. 87, 3221–3226 (2002)CrossRef PubMed
  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. 243–266
  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)
  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)CrossRef PubMed
  28.S. Kota, K.M. Lalit, S. Jammula, S.K. Kota, D.M. Kirtikumar, Clinical profile of coexisting conditions in type 1 diabetes mellitus patients. Diabetes Metab. Syndr. 6, 70–76 (2012)CrossRef PubMed
  29.A.L. Notkins, A. Lernmark, Autoimmune type 1 diabetes: resolved and unresolved issues. J. Clin. Invest. 108(12), 47–52 (2001)
  30.X.P. Cai, L. Zhao, M. Mao, A case of Klinefelter’s syndrome with type 1 diabetes mellitus. Chin. Med. J. 125(5), 937–940 (2012)PubMed
  31.K. Ota, T. Suehiro, Y. Ikeda, K. ArII, Y. Kumon, K. Hashimoto, Diabetes mellitus associated with Klinefelter’s syndrome: a case report and review in Japan. Intern. Med. 41(10), 842–847 (2002)CrossRef PubMed
  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)CrossRef PubMed
  33.C. Verge, E. Gianani, L. Kawasaki et al., Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 45, 926–993 (1996)CrossRef PubMed
  34.N.K. Mclaren, M.S. Lan, D. Schatz et al., Multiple autoantibodies as predictors of type 1 diabetes in a general population. Diabetologia 46(6), 873–874 (2003)CrossRef
  35.J.M. Barker, J. Yu, L. Yu et al., Autoantibody “subspecificity” in type 1 diabetes: risk for organ-specific autoimmunity clusters in distinct groups. Diabetes Care 28, 850–855 (2005)CrossRef PubMed
  36.M. Pietropaolo, R. Towns, G.S. Eisenbarth, Humoral autoimmunity in type 1 diabetes: prediction, significance, and detection of distinct disease subtypes. Cold Spring Harb. Perspect. Med. 2(10), 1–18 (2012)CrossRef
  37.O. Kordonouri, D. Deiss, T. Danne et al., Predictivity of thyroid autoantibodies for the development of thyroid disorders in children and adolescents with Type 1 diabetes. Diabet. Med. 19(6), 518–521 (2002)CrossRef PubMed
  38.I.H. Kocar, Z. Yesilova, M. Ozata et al., The effect of testosterone replacement treatment on immunological features of patients with Klinefelter’s syndrome. Clin. Exp. Immunol. 121, 448–452 (2000)CrossRef PubMed PubMedCentral
  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)CrossRef PubMed
  40.J. Visootsak, J.M. Graham Jr, Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J. Rare Dis. 1, 42 (2006)CrossRef PubMed PubMedCentral
  
• 作者单位：Francesca Panimolle (1)
  Claudio Tiberti (1)
  Simona Granato (1)
  Antonella Semeraro (1)
  Daniele Gianfrilli (1)
  Antonella Anzuini (1)
  Andrea Lenzi (1)
  Antonio Radicioni (1)
  
  1. Section of Medical Pathophysiology, Department of Experimental Medicine, Center of Rare Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
  
• 刊物主题：Endocrinology; Diabetes; Internal Medicine; Science, general;
• 出版者：Springer US
• ISSN：1559-0100

文摘

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.