ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1069

Child’s HLA-DRB1 Genotype Increases Maternal Risk of Systemic Lupus Erythematosus: Results from the Mother-Child Immunogenetic Study in Autoimmunity

Giovanna I. Cruz1, Xiaorong Shao2, Hong L. Quach2, Janelle Noble3, Nikolaos Patsopoulos4, Michael Busch5, Darrell Triulzi6, Wendy S.W. Wong7, Benjamin Solomon7, John Niederhuber7, Lindsey A. Criswell8 and Lisa F. Barcellos2, 1School of Public Health, University of California, Berkeley, Berkeley, CA, 2Genetic Epidemiology and Genomics Laboratory, University of California, Berkeley, Berkeley, CA, 3Children's Hospital Oakland Research Institute, Oakland, CA, 4Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, 5Blood Systems Research Institute, San Francisco, CA, 6Institute of Transfusion Medicine, University of Pittsburgh, Pittsburgh, PA, 7Division of Medical Genomics, Inova Translational Medicine Institute, Falls Church, VA, 8Rosalind Russell / Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, San Francisco, CA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , ,

Session Information

Date: Sunday, November 8, 2015

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: Genetics, Gene Expression, and Epigenetics

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: SLE [MIM 152700] disproportionately affects women of reproductive age and pregnant patients are more likely to experience flares. Fetal microchimerism (FMC), or the persistence of a small population of cells in the mother, is a natural consequence of pregnancy. Risk of SLE is possibly increased through fetal HLA-antigen molecular mimicry. The causes of SLE are unknown but genetic and environmental factors, including Epstein-Barr virus (EBV) infection, are suspected. The strongest genetic association is with HLA-DRB1 alleles *03:01, *15:01, *08:01. We hypothesize that compared to controls, SLE cases are more likely to have children with a) DRB1-associated risk alleles and/or b) DRB1*04:01that encodes a homologous amino acid sequence to EBV. 

Methods: We investigated mother-child HLA relationships in 218 SLE and 349 control mothers (and their 881 children) from the Mother-Child Immunogenetic Study (MCIS). The MCIS is a study with over 9,000 individuals: cases were recruited at UC San Francisco; controls were recruited from the Blood Centers of the Pacific, the Institute for Transfusion Medicine at the University of Pittsburgh, and from studies at the Inova Translational Medicine Institute (ITMI). Comprehensive MHC region SNP genotyping was conducted using the Illumina MHC, ImmunoChip, and 660K arrays for MCIS participants and whole genome sequencing for ITMI controls. Classical two-field HLA alleles were imputed using SNP2HLA. Clinical data were abstracted from medical records. We selected mothers of European ancestry using multidimensional scaling and ancestry informative markers to minimize any impact of population stratification. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SLE and having any children who carry DRB1 risk alleles or DRB1*04:01. 

Results: Initial findings reveal an increased risk of SLE among mothers with children who carry DRB1*15:01 (OR 2.26; 95% CI, 1.39-3.66) and *04:01 (OR 1.73; 95% CI, 1.14-2.64), both adjusted for maternal genotype. Furthermore, we observed a stronger association between children who carry DRB1*15:01and the SLE complication lupus nephritis compared to controls (OR 2.75; 95% CI, 1.12-6.76, n=383).

Conclusion: These findings support the hypothesis that a child’s genotype influences a mother’s risk of disease, independent of the mother’s genotype. This is the first study to demonstrate an association between a child’s DRB1 genotype and risk of SLE in the mother.

Disclosure: G. I. Cruz, None; X. Shao, None; H. L. Quach, None; J. Noble, None; N. Patsopoulos, None; M. Busch, None; D. Triulzi, None; W. S. W. Wong, None; B. Solomon, None; J. Niederhuber, None; L. A. Criswell, None; L. F. Barcellos, None.

To cite this abstract in AMA style:

Cruz GI, Shao X, Quach HL, Noble J, Patsopoulos N, Busch M, Triulzi D, Wong WSW, Solomon B, Niederhuber J, Criswell LA, Barcellos LF. Child’s HLA-DRB1 Genotype Increases Maternal Risk of Systemic Lupus Erythematosus: Results from the Mother-Child Immunogenetic Study in Autoimmunity [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/childs-hla-drb1-genotype-increases-maternal-risk-of-systemic-lupus-erythematosus-results-from-the-mother-child-immunogenetic-study-in-autoimmunity/. Accessed .

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