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X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome
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2016 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 68, no 5, 1290-1300 p.Article in journal (Refereed) Published
Abstract [en]


More than 80% of autoimmune disease is female dominant, but the mechanism for this female bias is poorly understood. We suspected an X chromosome dose effect and hypothesized that trisomy X (47,XXX, 1 in ∼1,000 live female births) would be increased in female predominant diseases (e.g. systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis [PBC] and rheumatoid arthritis [RA]) compared to diseases without female predominance (sarcoidosis) and controls.


We identified 47,XXX subjects using aggregate data from single nucleotide polymorphism (SNP) arrays and confirmed, when possible, by fluorescent in situ hybridization (FISH) or quantitative polymerase chain reaction (q-PCR).


We found 47,XXX in seven of 2,826 SLE and three of 1,033 SS female patients, but only in two of the 7,074 female controls (p=0.003, OR=8.78, 95% CI: 1.67-86.79 and p=0.02, OR=10.29, 95% CI: 1.18-123.47; respectively). One 47,XXX subject was present for ∼404 SLE women and ∼344 SS women. 47,XXX was present in excess among SLE and SS subjects.


The estimated prevalence of SLE and SS in women with 47,XXX was respectively ∼2.5 and ∼2.9 times higher than in 46,XX women and ∼25 and ∼41 times higher than in 46,XY men. No statistically significant increase of 47,XXX was observed in other female-biased diseases (PBC or RA), supporting the idea of multiple pathways to sex bias in autoimmunity. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
2016. Vol. 68, no 5, 1290-1300 p.
National Category
Rheumatology and Autoimmunity
URN: urn:nbn:se:uu:diva-273528DOI: 10.1002/art.39560ISI: 000375551600030PubMedID: 26713507OAI: oai:DiVA.org:uu-273528DiVA: diva2:894767
NIH (National Institute of Health), AR-062755;AI-024717;AI-031584;AI-062629;AI-063274;AI-082714;AI-083194;AI-101934Swedish Rheumatism AssociationGerman Research Foundation (DFG), KFO 250 WI 1031/6-1NIH (National Institute of Health), AR-042460 AR-048204 AR-048940 AR-049084 AR-052125 AR-053483 AR-053734 AR-056360 AR-058959 AR-062277 AR-043814 AR-065626 DE-015223 DE-018209 RR-020143 GM-103510 GM-104938 HG-008667 TR-001475 HG-006828
Available from: 2016-01-15 Created: 2016-01-15 Last updated: 2016-08-29Bibliographically approved

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