ArticleClinical immunology (Orlando, Fla.)2016
Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome.
Erratum issuedOpen access · greenAbstract readMulticenter Study
In one paragraph
Article in Clinical immunology (Orlando, Fla.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 2 pooled it
5.3field-weighted citation impact, top 4% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- The extra X chromosome and autoimmune susceptibility in Klinefelter syndrome.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- Sex steroids and autoimmune rheumatic diseases: state of the art.Nature reviews. Rheumatology · 2020Pooled it
- The X Factor in Immunity: Sex Differences Shaped by the X Chromosome.Immunological reviews · 2026Review
- Klinefelter syndrome beyond hypogonadism: multisystem manifestations and a framework for clinical surveillance.Frontiers in endocrinology · 2026Review
- TLR7 and TLR9 have overlapping but distinct roles in systemic lupus erythematosus and Sjögren's disease.Frontiers in immunology · 2026Review
- Sex Bias in Autoimmunity: New Findings and New Opportunities.JID innovations : skin science from molecules to population health · 2025Review
- The Therapeutic Potential of Phytochemicals Unlocks New Avenues in the Management of Rheumatoid Arthritis.International journal of molecular sciences · 2025Review
- Genetic, Transcriptomic, and Epigenomic Insights into Sjögren's Disease: An Integrative Network Investigation and Immune Diseases Comparison.International journal of molecular sciences · 2025Article
- The Inactive X Chromosome: A Genetic Driver of Female-Biased Rheumatic Autoimmune Disorders?European journal of immunology · 2025Review
- Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes.The Journal of experimental medicine · 2025Article
- More X's, more problems: how contributions from the X chromosomes enhance female predisposition for autoimmunity.Current opinion in immunology · 2025Review
- Review
- The toll like receptor 7 pathway and the sex bias of systemic lupus erythematosus.Frontiers in immunology · 2025Article
- Synergistic Effects of Extra X Chromosome on Development of Systemic Lupus Erythematosus and Sjögren Disease in Klinefelter and Triple X Syndrome: A Retrospective Cohort Study.ACR open rheumatology · 2025Article
- Vitamin D in Primary Sjogren's Syndrome (pSS) and the Identification of Novel Single-Nucleotide Polymorphisms Involved in the Development of pSS-Associated Diseases.Diagnostics (Basel, Switzerland) · 2024Review
- Sex difference in human diseases: mechanistic insights and clinical implications.Signal transduction and targeted therapy · 2024Review
- Review
- Male patients with primary Sjögren's syndrome have unique clinical manifestations and circulating lymphocyte profiles.Clinical rheumatology · 2024Article
- Long Non-Coding RNAs in Sjögren's Disease.International journal of molecular sciences · 2024Review
- Altered X-chromosome inactivation predisposes to autoimmunity.Science advances · 2024Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
49 authors at 20 institutions in 11 countries.
Valerie M HarrisArthritis & 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.
Rohan SharmaDepartment 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.
Joshua CavettArthritis & 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.
Biji T KurienArthritis & 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.
Ke LiuCenter for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
Kristi A KoelschArthritis & 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.
Astrid RasmussenArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Lida RadfarDepartment of Oral Diagnosis and Radiology, College of Dentistry, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
David LewisDepartment of Oral Diagnosis and Radiology, College of Dentistry, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Donald U StoneDean McGee Eye Institute and Department of Ophthalmology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA.
C Erick KaufmanDepartment of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Shibo LiDepartment of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Barbara SegalDepartment of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Daniel J WallaceDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Michael H WeismanDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Swamy VenuturupalliDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jennifer A KellyArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Marta E Alarcon-RiquelmeArthritis & 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.
Bernardo Pons-EstelSanatorio Parque, Rosario, Argentina.
Roland JonssonBroegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen 5021, Norway; Department of Rheumatology, Haukeland University Hospital, Bergen 5021, Norway.
Xianglan LuDepartment of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Jacques-Eric GottenbergStrasbourg University, Strasbourg, France.
Juan-Manuel AnayaCenter for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia.
Deborah S Cunninghame-GrahamDivision of Genetics and Molecular Medicine and Division of Immunology, Infection and Inflammatory Disease, King's College London, London, UK.
Andrew J W HuangDepartment of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, MN, USA.
Michael T BrennanDepartment of Oral Medicine, Carolinas Medical Center, Charlotte, NC 28232, USA.
Pamela HughesDepartment of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, MN, USA.
Ilias AlevizosMolecular Physiology & Therapeutic Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.
Corinne Miceli-RichardDepartment of Rheumatology, Université Paris-Sud, AP-HP, INSERM U1012, Le Kremlin-Bicêtre, France.
Edward C KeystoneDepartment of Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada.
Vivian P BykerkHospital for Special Surgery, New York, USA.
Gideon HirschfieldNIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK.
Gang XieSamuel Lunenfeld and Toronto General Research Institutes, Departments of Medicine, Immunology and Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Katherine A Siminovitch
Wan-Fai NgMusculoskeletal Research Group, Institute of Cellular Medicine & NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK.
Gunnel NordmarkSection of Rheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Sara Magnusson BucherDepartment of Rheumatology, Örebro University Hospital, Örebro, Sweden.
Per ErikssonClinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
Roald OmdalRheumatology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Nelson L RhodusDepartment of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, USA.
Maureen RischmuellerRheumatology Department, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, Australia.
Michael RohrerDepartment of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, MN, USA.
Marie Wahren-HerleniusRheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Torsten WitteClinic for Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany.
Xavier MarietteDepartment of Rheumatology, Université Paris-Sud, AP-HP, INSERM U1012, Le Kremlin-Bicêtre, France.
Christopher J LessardArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
John B HarleyCenter 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.
Kathy L SivilsArthritis & 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.
R Hal ScofieldArthritis & 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.
Oklahoma Medical Research Foundation · USUniversity of Oklahoma Health Sciences Center · USCedars-Sinai Medical Center · USUniversity of Minnesota · USCincinnati Children's Hospital Medical Center · USUniversité Paris-Sud · FRCarolinas Medical Center · USCentro Científico Tecnólogico - Rosario · ARDean McGee Eye Institute · USHaukeland University Hospital · NOHospital for Special Surgery · USKarolinska Institutet · SEKing's College London · GBLinköping University · SEMedizinische Hochschule Hannover · DEMount Sinai Hospital · CANational Institutes of Health · USNIHR Birmingham Biomedical Research Centre · GBNIHR Newcastle Biomedical Research Centre · GBÖrebro University · SE
Funding
Tracking and Evaluation CoreU54GM104938 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI PAUL G SPICER · 2013 to 2026
$68.2MClinical Investigations of Sjogren's SyndromeZIADE000704 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI WARNER, BLAKE · 2009 to 2025
$22.3MPathogenic B Cells in Sjogren's SyndromeP50AR060804 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI SIVILS, KATHY L. · 2011 to 2015
$7.9MSNP Confirmation and High Throughput Genotyping CoreP30AR053483 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI CHAKRAVARTY, ELIZA F · 2007 to 2017
$6.7MPre-Clinical Studies to Identify SLE Therapeutic TargetsU19AI082714 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI GAFFNEY, PATRICK M · 2009 to 2018
$6.2MThe X Chromosome in Systemic Lupus ErythematosusR01AR053734 · NIAMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SCOFIELD, ROBERT HAL · 2006 to 2010
$1.4MSex Chromosome Aneuploidies in Autoimmune DiseaseI01BX001451 · VA · OKLAHOMA CITY VA MEDICAL CENTER · PI SCOFIELD, ROBERT HAL · 2012 to 2025
–BLRD VA I01 BX001451Intramural VA VA999999Medical Research Council G0800629NIAID NIH HHS U19 AI082714NIAMS NIH HHS P30 AR053483NIAMS NIH HHS P50 AR060804NIAMS NIH HHS R01 AR053734NIGMS NIH HHS U54 GM104938
Abstract
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.
Indexed as
Arthritis, RheumatoidChromosomes, Human, XChromosomes, Human, YFemaleGene FrequencyGenotypeHumansKlinefelter SyndromeLupus Erythematosus, SystemicMalePolymorphism, Single NucleotideSjogren's SyndromeKlinefelter's syndromeSex biasSjögren's syndromeX chromosome
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