Evidence map›Paper›PMID 26713507›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2016

X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome.

Ke Liu, Biji T Kurien, Sarah L Zimmerman, Kenneth M Kaufman, Diana H Taft, Leah C Kottyan, Sara Lazaro, Carrie A Weaver, John A Ice, Adam J Adler and 68 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 3 pooled it
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

103 citing papers in PubMed, 3 syntheses or guidelines pooled it, 170 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Review
  5. Sex-dependent mechanisms in rheumatic diseases.Nature reviews. Rheumatology · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Decidual CD4 Effector Memory and Resident Memory T Cells Respond to Cord Blood Allo-Antigens.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Sex Bias in Autoimmunity: New Findings and New Opportunities.JID innovations : skin science from molecules to population health · 2025
    Review
  18. Review
  19. Review
  20. Article

43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

78 authors at 20 institutions in 11 countries.

Ke LiuCenter for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Biji T KurienCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Sarah L ZimmermanDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Kenneth M KaufmanCenter for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Diana H TaftCenter for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Leah C KottyanCenter for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Sara LazaroCenter for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Carrie A WeaverCenter for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
John A IceArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Adam J AdlerArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
James ChodoshDepartment of Ophthalmology, Howe Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
Lida RadfarDepartment of Oral Diagnosis and Radiology, College of Dentistry, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Astrid RasmussenArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Donald U StoneDean McGee Eye Institute and Department of Ophthalmology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA.
David M LewisDepartment of Oral Diagnosis and Radiology, College of Dentistry, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Shibo LiCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Kristi A KoelschCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Ann IgoeCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Mitali TalsaniaCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Jay KumarCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Jacen S Maier-MooreCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Valerie M HarrisCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Rajaram GopalakrishnanDepartment of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, MN, USA.
Roland JonssonBroegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen 5021, Norway.
James A LessardValley Bone & Joint Clinic, 3035 DeMers Avenue, Grand Forks, ND 58201, USA.
Xianglan LuCollege 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.
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.
Gabor G IlleiSjögren's Syndrome Clinic, National Institute of Dental and Craniofacial Research, Molecular Physiology and Therapeutics Branch, National Institutes of Health, Bethesda, MD 20892, 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.
Vivian P BykerkHospital for Special Surgery, New York, USA.
Gideon HirschfieldNIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK.
Gang XieLunenfeld Tanenbaum and Toronto General Research Institutes, Departments of Medicine, Immunology and Molecular Genetics, University of Toronto, Toronto Ontario.
Wan-Fai NgMusculoskeletal Research Group, Institute of Cellular Medicine & NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, United Kingdom.
Gunnel NordmarkSection of Rheumatology, Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Per ErikssonRheumatology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Roald OmdalClinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
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.
Michael RohrerDepartment of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, MN, USA.
Barbara M SegalDepartment of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Timothy J VyseDivision of Genetics and Molecular Medicine and Division of Immunology, Infection and Inflammatory Disease, King's College London, London.
Marie Wahren-HerleniusRheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Torsten WitteClinic for Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany.
Bernardo Pons-EstelSanatorio Parque, Rosario, Argentina.
Marta E Alarcon-RiquelmeArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Joel M GuthridgeCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Judith A JamesCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Christopher J LessardCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Jennifer A KellyArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Susan D ThompsonCenter for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Patrick M GaffneyArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Courtney G MontgomeryArthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Jeffrey C EdbergDivision of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, AL.
Robert P KimberlyDivision of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, AL.
Graciela S AlarcónDivision of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, AL.
Carl L LangefeldCenter for Public Health Genomics and Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University, Winston-Salem, NC.
Gary S GilkesonDivision of Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC.
Diane L KamenDivision of Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC.
Betty P TsaoDivision of Rheumatology, Department of Medicine, UCLA School of Medicine.
W Joseph McCuneDivision of Rheumatology, Department of Medicine, University of Michigan College of Medicine, Ann Arbor, Michigan.
Jane E SalmonDivision of Rheumatology, Hospital for Special Surgery and Weill Cornell Medical College, New York, NY.
Joan T MerrillCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Michael H WeismanDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA.
Daniel J WallaceDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA.
Tammy O UtsetUniversity of Chicago Pritzker School of Medicine, Chicago, IL.
Erwin P BottingerCharles R. Bronfman Institute for personalized medicine, Mount Sinai Hospital, 1468 Madison Avenue, New York, NY 10029.
Christopher I AmosDepartment of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
Katherine A SiminovitchLunenfeld Tanenbaum and Toronto General Research Institutes, Departments of Medicine, Immunology and Molecular Genetics, University of Toronto, Toronto Ontario.
Xavier MarietteRhumatologie, Responsable de l'Unité de Recherche Clinique Hôpitaux Universitaire Paris-Sud Université Paris-Sud, INSERM U1184 Head of Autoimmunity team, IMVA : Immunology of viral Infections and Autoimmune Diseases.
Kathy L SivilsCollege of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
John B Harley *Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
R Hal Scofield *College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
University of Oklahoma Health Sciences Center · USOklahoma Medical Research Foundation · USCincinnati Children's Hospital Medical Center · USUniversity of Alabama at Birmingham · USUniversity of Minnesota System · USUniversity of Toronto · CAKing's College London · GBOklahoma City VA Medical Center · USRalph H. Johnson VA Medical Center · USUniversity of California, Los Angeles · USUniversity of Minnesota · USCarolinas Medical Center · USCedars-Sinai Medical Center · USCentro Científico Tecnólogico - Rosario · ARCincinnati VA Medical Center · USDartmouth College · USDean McGee Eye Institute · USHospital for Special Surgery · USInserm · FRKarolinska Institutet · SE

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
Tracking and Evaluation CoreU54GM104938 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI JENNIFER DAVID PECK · 2013 to 2026
$68.2M
Translation of immunologic technologies from basic research into pre-clinical nonU19AI062629 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI FARRIS, A DARISE · 2004 to 2023
$56.2M
UAB Center for Clinical and Translational Science (CCTS)UL1TR001417 · NCATS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KIMBERLY, ROBERT P. · 2015 to 2018
$31.4M
VALIDATING NOVEL GENES IMPLICATED IN LEUKOCYTE CHEMOTAXISP20RR020143 · NCRR · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI KAUFMAN, KENNETH M · 2004 to 2011
$21.0M
Pediatric Rheumatology Tissue RepostoryP01AR048929 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI THOMPSON, SUSAN D · 2003 to 2015
$13.6M
Program Project in the Genetics of SLEP01AR049084 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KIMBERLY, ROBERT P. · 2002 to 2012
$12.7M
SequencingP01AI083194 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI LANGEFELD, CARL D · 2009 to 2013
$9.6M
ROLE OF ANGPTL4, AN ANGIOGENIC MEDIATOR, IN ARTHRITISP30AR047363 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI THOMPSON, SUSAN D · 2001 to 2015
$9.2M
Comprehensive Genome Interrogation of African American Sarcoidosis FamiliesR01HL113326 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI MONTGOMERY, COURTNEY · 2012 to 2022
$8.7M
Pathogenic B Cells in Sjogren's SyndromeP50AR060804 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI SCOFIELD, ROBERT HAL · 2011 to 2015
$7.9M
HLA GENE COMPLEMENTATION IN PRIMARY SJOGREN'S AND LUPUSR01AI024717 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI KOTTYAN, LEAH CLAIRE, WEIRAUCH, MATTHEW TYSON · 1987 to 2025
$7.8M
BLRD VA I01 BX001451CIHR MOP74621CIHR MOP89955Medical Research Council G0800629NCATS NIH HHS UL1 TR001417NCI NIH HHS P30 CA023108NCRR NIH HHS P20 RR020143NHGRI NIH HHS U01 HG006828NHLBI NIH HHS R01 HL113326NIAID NIH HHS P01 AI083194NIAID NIH HHS R01 AI024717NIAID NIH HHS R01 AI031584NIAID NIH HHS R01 AI063274NIAID NIH HHS R37 AI024717NIAID NIH HHS R56 AI063274NIAID NIH HHS U01 AI101934NIAID NIH HHS U19 AI062629NIAID NIH HHS U19 AI082714NIAMS NIH HHS N01 AR062277NIAMS NIH HHS P01 AR048929NIAMS NIH HHS P01 AR049084NIAMS NIH HHS P30 AR047363NIAMS NIH HHS P30 AR053483NIAMS NIH HHS P30 AR070549NIAMS NIH HHS P50 AR048940NIAMS NIH HHS P50 AR060804NIAMS NIH HHS P60 AR062755NIAMS NIH HHS R01 AR042460NIAMS NIH HHS R01 AR043814NIAMS NIH HHS R01 AR052125NIAMS NIH HHS R01 AR053734NIAMS NIH HHS R01 AR056360NIAMS NIH HHS R01 AR057106NIAMS NIH HHS R21 AR065626NIAMS NIH HHS RC1 AR058587NIAMS NIH HHS RC2 AR058959NIDCR NIH HHS R01 DE015223NIDCR NIH HHS R01 DE018209NIGMS NIH HHS P30 GM103510NIGMS NIH HHS U54 GM104938
6 · The paper itself

Abstract

objectiveMore than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ∼1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls.

methodsAll subjects in this study were female. We identified subjects with 47,XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47,XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction.

resultsWe found 47,XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47,XXX. There was an excess of 47,XXX among SLE and SS patients.

conclusionThe estimated prevalence of SLE and SS in women with 47,XXX was ∼2.5 and ∼2.9 times higher, respectively, than that in women with 46,XX and ∼25 and ∼41 times higher, respectively, than that in men with 46,XY. No statistically significant increase of 47,XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity.

Indexed as

Arthritis, RheumatoidAutoimmune DiseasesCase-Control StudiesChromosomes, Human, XFemaleGene DosageHumansIn Situ Hybridization, FluorescenceLiver Cirrhosis, BiliaryLupus Erythematosus, SystemicPrevalenceSarcoidosisSex Chromosome AberrationsSex Chromosome Disorders of Sex DevelopmentSex DistributionSjogren's Syndrome

Identifiers

PMID26713507
PMCPMC5019501
OpenAlexW2409599897

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.