Klinefelter's Syndrome (47,XXY) Among Men with Sjögren's Syndrome

Valerie M Harris¹, Joshua Cavett², Biji Kurien³, Ke Liu⁴, Kristi A. Koelsch⁵, Lida Radfar⁶, David M. Lewis⁷, Donald U. Stone⁸, Shibo Li⁹, Barbara Segal¹⁰, Daniel J Wallace¹¹, Michael H. Weisman¹², Jennifer A. Kelly¹³, Marta Alarcon-Riquelme¹⁴, Bernado Pons-Estel¹⁵, Roland Jonsson¹⁶, Xianglan Lu⁹, Jacques Gottenberg¹⁷, Juan-Manuel Anaya¹⁸, Deborah S. Cunninghame-Graham¹⁹, Edward C. Keystone²⁰, Andrew J.W. Huang²¹, Michael T. Brennan²², Pamela Hughes²³, G Illei²⁴, Corinne Miceli²⁵, VP Bykerk²⁶, Gideon Hirschfield²⁷, Gang Xie²⁸, Wan-Fai Ng²⁹, Gunnel Nordmark³⁰, Per Eriksson³¹, Roald Omdal³², Nelson L. Rhodus³³, Maureen Rischmueller³⁴, Michael D. Rohrer³⁵, Marie Wahren-Herlenius³⁶, Torsten Witte³⁷, Xavier Mariette³⁸, Christopher Lessard³⁹, John B. Harley⁴⁰, Kathy L. Sivils³⁹ and Robert Hal Scofield⁴¹, ¹Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, ²Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, ³Arthritis and Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, ⁴3333 Burnet Ave., University of Cincinnati & Cincinnati Childre, Cincinnati, OH, ⁵Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Okalahoma City, OK, ⁶Oral Diagnosis and Radiology Department, University of Oklahoma Health Sciences Center College of Dentistry, Oklahoma City, OK, ⁷College of Dentistry, Department of Oral and Maxillofacial Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, ⁸King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, ⁹Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, ¹⁰Rheumatology, Univ of Minnesota, Minneapolis, MN, ¹¹Cedars-Sinai Medical Center, West Hollywood, CA, ¹²Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, ¹³Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, ¹⁴Arthritis & Clinical Immunology, Oklahoma Medical REsearch Foundtion, Oklahoma City, OK, ¹⁵Hospital Provincial de Rosario, Rosario, Argentina, ¹⁶Broegelmann research laboratory, Bergen, Norway, ¹⁷Hautepierre, Strasbourg, France, ¹⁸Cell Biol and Immunogenetics, CIB-Rosario University, Medellin, Colombia, ¹⁹Department of Medical and Molecular Genetics, King's College London, London, United Kingdom, ²⁰Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, ²¹Department of Ophthalmology and Visual Sciences, Washington University, St Louis, MO, ²²Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, ²³Division of Oral and Maxillofacial Surgery, Department of Developmental and Surgical Science, University of Minnesota School of Dentistry, Minneapolis, MN, ²⁴Sjögren's Clinic, NIDCR/NIH, Bethesda, MD, ²⁵Rheumatology, PARIS, France, ²⁶University of Toronto, Toronto, ON, Canada, ²⁷Centre for Liver Research, Institute of Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom, ²⁸Mount Sinai Hospital, Toronto, ON, Canada, ²⁹Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom, ³⁰Medical Sciences, Uppsala University, Uppsala, Sweden, ³¹University Hospital, Rheumatology clinic, Linköping, Sweden, ³²Department of internal medicine, Clinical Immunology unit, Stavanger, Norway, ³³Department of Oral Surgery, University of Minnesota School of Dentistry, Minneapolis, MN, ³⁴Rheumatology, Queen Elizabeth Hospital, Adelaide, Australia, ³⁵Hard Tissue Research Laboratory, University of Minnesota School of Dentistry, Minneapolis, MN, ³⁶Department of Medicine, Experimental Rheumatology Unit, Solna, Sweden, ³⁷Department of Immunology and Rheumatology, Hannover Medical School, Hannover, Germany, ³⁸Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, Paris, France, ³⁹Oklahoma Medical Research Foundation, Oklahoma City, OK, ⁴⁰Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ⁴¹Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation; Department of Medicine, University of Oklahoma Health Sciences Center; US Department of Veterans Affairs Medical Center, Oklahoma City, OK

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: genetics and sex bias, Sjogren's syndrome, X chromosome

Session Information

Date: Sunday, November 8, 2015

Title: Sjögren's Syndrome Poster I: Clinical Insights into Sjögren's Syndrome

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Primary Sjögren’s syndrome (pSS) has a strong female bias of greater than 10 to 1. This difference in risk of disease between the sexes has not been explained. We hypothesize that the number of X chromosomes is important for this bias, and that examination of patients for rare X chromosome aneuploides will inform the sex bias for those with a normal chromosome complement.

Methods:

We evaluated the hypothesis of an X chromosome dose effect by analyzing the presence of 47,XXY (Klinefelter’s syndrome, 1 in 500 live male births) among a large cohort of subjects with pSS. All subjects with pSS met the American-European Consensus Classification Criteria for Sjögren’s syndrome. The presence of extranumerary X chromosomes was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes from either Illumina genome-wide association study platform or the ImmunoChip. Karyotype or fluorescent in situ hybridization confirmed some of these results.

Results: Among 126 pSS men, there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47,XXY, p=0.0012 by Fisher’s exact test) as well as when compared to men with rheumatoid arthritis and the expected population frequency, but not different from published results in men with systemic lupus erythematosus (SLE). Using Bayes’ theorem along with the population prevalence of Sjögren’s and Klinefelter’s syndromes as well as the finding of ~1 in 30 Sjögren’s men with 47,XXY, we calculate that men with Klinefelter’s syndrome have a risk of pSS about equal to that of women.

Conclusion: Combined with our previous data that 3 of 1,033 SS women, but only in two of the 7,074 female controls, have 47,XXX, which is found in 1 in 1000 live female births (p=0.02, OR=10.29, 95% CI: 1.18-123.47), these results are consistent with the hypothesis that the number of X chromosomes is important for the sex bias of pSS.

Disclosure: V. M. Harris, None; J. Cavett, None; B. Kurien, None; K. Liu, None; K. A. Koelsch, None; L. Radfar, None; D. M. Lewis, None; D. U. Stone, None; S. Li, None; B. Segal, None; D. J. Wallace, None; M. H. Weisman, None; J. A. Kelly, None; M. Alarcon-Riquelme, None; B. Pons-Estel, None; R. Jonsson, None; X. Lu, None; J. Gottenberg, None; J. M. Anaya, None; D. S. Cunninghame-Graham, None; E. C. Keystone, Janssen Inc., 2,Abbott/AbbVie, 5,Amgen, 2,Bristol-Myers Squibb, 5,Janssen Inc., 5,Hoffmann-La Roche, Inc., 5,Janssen Inc., 2,Janssen Inc., 5,Merck Pharmaceuticals, 5,Merck Pharmaceuticals, 5,Pfizer Pharmaceuticals, 5,Pfizer Pharmaceuticals, 5; A. J. W. Huang, None; M. T. Brennan, None; P. Hughes, None; G. Illei, AstraZeneca, 1,MedImmune, 3; C. Miceli, None; V. Bykerk, None; G. Hirschfield, None; G. Xie, None; W. F. Ng, None; G. Nordmark, None; P. Eriksson, None; R. Omdal, None; N. L. Rhodus, None; M. Rischmueller, None; M. D. Rohrer, None; M. Wahren-Herlenius, None; T. Witte, None; X. Mariette, Biogen Idec, 2,Pfizer Inc, 2,Bristol-Myers Squibb, 5,Pfizer Inc, 5,AstraZeneca, 5,GlaxoSmithKline, 5; C. Lessard, None; J. B. Harley, None; K. L. Sivils, Lilly, 2; R. H. Scofield, Lilly, UCB, 5.

To cite this abstract in AMA style:

Harris VM, Cavett J, Kurien B, Liu K, Koelsch KA, Radfar L, Lewis DM, Stone DU, Li S, Segal B, Wallace DJ, Weisman MH, Kelly JA, Alarcon-Riquelme M, Pons-Estel B, Jonsson R, Lu X, Gottenberg J, Anaya JM, Cunninghame-Graham DS, Keystone EC, Huang AJW, Brennan MT, Hughes P, Illei G, Miceli C, Bykerk V, Hirschfield G, Xie G, Ng WF, Nordmark G, Eriksson P, Omdal R, Rhodus NL, Rischmueller M, Rohrer MD, Wahren-Herlenius M, Witte T, Mariette X, Lessard C, Harley JB, Sivils KL, Scofield RH. Klinefelter’s Syndrome (47,XXY) Among Men with Sjögren’s Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/klinefelters-syndrome-47xxy-among-men-with-sjogrens-syndrome/. Accessed .

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