title: A Child's HLA-DRB1 genotype increases maternal risk of systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) disproportionately affects women of reproductive age. During pregnancy, women are exposed to various sources of fetal material possibly constituting a significant immunologic exposure relevant to the development of SLE. The objective of this study was to investigate whether having any children who carry DRB1 alleles associated with SLE increase the risk of maternal SLE. This case-control study is based on the University of California, San Francisco Mother-Child Immunogenetic Study and from studies at the Inova Translational Medicine Institute. Analyses were conducted using data for 1304 mothers (219 cases/1085 controls) and their respective 1664 children. We selected alleles based on their known association with risk of SLE (DRB1*03:01, *15:01, or *08:01) or Epstein-Barr virus (EBV) glycoproteins (*04:01) due to the established EBV association with SLE risk. We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for each allele of interest, taking into account maternal genotype and number of live births. We found an increase in risk of maternal SLE associated with exposure to children who inherited DRB1*04:01 from their father (OR 1.9; 95% CI, 1.1-3.2), among *04:01 allele-negative mothers. Increased risk was only present among mothers who were positive for one or more SLE risk-associated alleles (*03:01, *15:01 and/or *08:01). We did not find increased risk of maternal SLE associated with any other tested allele. These findings support the hypothesis that a child's alleles inherited from the father influence a mother's subsequent risk of SLE.
authors.affiliation: Genetic Epidemiology and Genomics Lab, Division of Epidemiology, School of Public Health, University of California Berkeley, 324 Stanley Hall, Berkeley, CA 94720-3220, USA. Electronic address: gcruz@berkeley.edu.
authors.forename: Giovanna I
authors.initials: GI
authors.lastname: Cruz
authors.affiliation: Genetic Epidemiology and Genomics Lab, Division of Epidemiology, School of Public Health, University of California Berkeley, 324 Stanley Hall, Berkeley, CA 94720-3220, USA. Electronic address: xshao@berkeley.edu.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Shao
authors.affiliation: Genetic Epidemiology and Genomics Lab, Division of Epidemiology, School of Public Health, University of California Berkeley, 324 Stanley Hall, Berkeley, CA 94720-3220, USA. Electronic address: hquach@berkeley.edu.
authors.forename: Hong
authors.initials: H
authors.lastname: Quach
authors.affiliation: Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Department of Medicine, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94122, USA. Electronic address: ho.kimberly@gmail.com.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Ho
authors.affiliation: Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Department of Medicine, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94122, USA. Electronic address: thesterbas@gmail.com.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sterba
authors.affiliation: Children's Hospital Oakland Research Institute, 5700 M.L.K. Jr. Way, Oakland, CA 94609, USA. Electronic address: jnoble@chori.org.
authors.forename: Janelle A
authors.initials: JA
authors.lastname: Noble
authors.affiliation: Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Program in Translational Neuropsychiatric Genomics, Institute for the Neurosciences, Department of Neurology, Brigham & Women's Hospital, 75 Francis Street, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Electronic address: npatsopoulos@rics.bwh.harvard.edu.
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Patsopoulos
authors.affiliation: Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, CA 94118-4417, USA. Electronic address: mbusch@bloodsystems.org.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.affiliation: Institute for Transfusion Medicine, Department of Pathology, University of Pittsburgh, 3636 Blvd. of the Allies, Pittsburgh, PA 15213, USA. Electronic address: DTriulzi@itxm.org.
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Triulzi
authors.affiliation: Division of Medical Genomics, Inova Translational Medicine Institute, 8110 Gatehouse Road, Falls Church, VA 22042, USA. Electronic address: ShukwanWendy.Wong@inova.org.
authors.forename: Wendy S W
authors.initials: WS
authors.lastname: Wong
authors.affiliation: Division of Medical Genomics, Inova Translational Medicine Institute, 8110 Gatehouse Road, Falls Church, VA 22042, USA. Electronic address: Benjamin.Solomon@inova.org.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Solomon
authors.affiliation: Division of Medical Genomics, Inova Translational Medicine Institute, 8110 Gatehouse Road, Falls Church, VA 22042, USA. Electronic address: John.Niederhuber@inova.org.
authors.forename: John E
authors.initials: JE
authors.lastname: Niederhuber
authors.affiliation: Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, Department of Medicine, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94122, USA. Electronic address: Lindsey.Criswell@ucsf.edu.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.affiliation: Genetic Epidemiology and Genomics Lab, Division of Epidemiology, School of Public Health, University of California Berkeley, 324 Stanley Hall, Berkeley, CA 94720-3220, USA; California Institute for Quantitative Biosciences (QB3), University of California Berkeley, 174 Stanley Hall, Berkeley, CA 94720-3220, USA. Electronic address: lbarcellos@berkeley.edu.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
mesh_terms: D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000209:etiology*; D008431:Maternal-Fetal Exchange / Q000235:genetics* / Q000276:immunology*; D008875:Middle Aged; D016017:Odds Ratio; D011247:Pregnancy
chemical_list: D001323:Autoantibodies; D059811:HLA-DRB1 Chains
keywords: Genetic epidemiology; Human leukocyte antigen genes; Pregnancy; Systemic lupus erythematosus