Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome.
Primary Sjögren's syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelter's syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 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 men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fisher's exact test p=NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA.
Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Pathology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Valerie M
VM
Harris
Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Medical Service, Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA.
Rohan
R
Sharma
Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Joshua
J
Cavett
Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Medical Service, Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA.
Biji T
BT
Kurien
Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
Ke
K
Liu
Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Medical Service, Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA.
Kristi A
KA
Koelsch
Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Astrid
A
Rasmussen
Department of Oral Diagnosis and Radiology, College of Dentistry, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Lida
L
Radfar
Department of Oral Diagnosis and Radiology, College of Dentistry, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
David
D
Lewis
Dean McGee Eye Institute and Department of Ophthalmology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA.
Donald U
DU
Stone
Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
C Erick
CE
Kaufman
Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Shibo
S
Li
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Barbara
B
Segal
Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Daniel J
DJ
Wallace
Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Michael H
MH
Weisman
Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Swamy
S
Venuturupalli
Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Jennifer A
JA
Kelly
Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Center Pfizer, University of Granada, Andalusian Government for Genomics and Oncological Research, PTS Granada, 18016, Spain.
Marta E
ME
Alarcon-Riquelme
Sanatorio Parque, Rosario, Argentina.
Bernardo
B
Pons-Estel
Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen 5021, Norway; Department of Rheumatology, Haukeland University Hospital, Bergen 5021, Norway.
Roland
R
Jonsson
Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Xianglan
X
Lu
Strasbourg University, Strasbourg, France.
Jacques-Eric
JE
Gottenberg
Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia.
Juan-Manuel
JM
Anaya
Division of Genetics and Molecular Medicine and Division of Immunology, Infection and Inflammatory Disease, King's College London, London, UK.
Deborah S
DS
Cunninghame-Graham
Department of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, MN, USA.
Andrew J W
AJW
Huang
Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC 28232, USA.
Michael T
MT
Brennan
Department of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, MN, USA.
Pamela
P
Hughes
Molecular Physiology & Therapeutic Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.
Ilias
I
Alevizos
Department of Rheumatology, Université Paris-Sud, AP-HP, INSERM U1012, Le Kremlin-Bicêtre, France.
Corinne
C
Miceli-Richard
Department of Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada.
Edward C
EC
Keystone
Hospital for Special Surgery, New York, USA.
Vivian P
VP
Bykerk
NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK.
Gideon
G
Hirschfield
Samuel Lunenfeld and Toronto General Research Institutes, Departments of Medicine, Immunology and Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Gang
G
Xie
Katherine A
KA
Siminovitch
Musculoskeletal Research Group, Institute of Cellular Medicine & NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK.
Wan-Fai
WF
Ng
Section of Rheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Gunnel
G
Nordmark
Department of Rheumatology, Örebro University Hospital, Örebro, Sweden.
Sara Magnusson
SM
Bucher
Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
Per
P
Eriksson
Rheumatology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Roald
R
Omdal
Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, USA.
Nelson L
NL
Rhodus
Rheumatology Department, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, Australia.
Maureen
M
Rischmueller
Department of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, MN, USA.
Michael
M
Rohrer
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Marie
M
Wahren-Herlenius
Clinic for Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany.
Torsten
T
Witte
Department of Rheumatology, Université Paris-Sud, AP-HP, INSERM U1012, Le Kremlin-Bicêtre, France.
Xavier
X
Mariette
Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Christopher J
CJ
Lessard
Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; College of Medicine, University of Cincinnati, Cincinnati, OH, USA; Medical Service, Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
John B
JB
Harley
Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Pathology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Kathy L
KL
Sivils
Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Pathology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Medical Service, Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA. Electronic address: hal-scofield@omrf.ouhsc.edu.
R Hal
RH
Scofield
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007713:Klinefelter Syndrome / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012859:Sjogren's Syndrome / Q000235:genetics*
Klinefelter's syndrome; Sex bias; Sjögren's syndrome; X chromosome