Associations between Systemic Lupus Susceptibility (SLE) Loci and Anti-Phospholipid Antibody (aPL) Positivity in Childhood-Onset SLE (cSLE)

Linda T Hiraki^1,2, France Gagnon³, Earl Silverman², Deborah M. Levy², Sima Abu Alsaoud⁴ and Karl Everett^1,3, ¹Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada, ²Division of Rheumatology, The Hospital for Sick Children, Toronto, ON, Canada, ³Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada, ⁴Rheumatology, The Hospital for Sick Children, Toronto, ON, Canada

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Antiphospholipid antibodies, genetics, pediatrics and systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 6, 2017

Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects Poster II: Lupus and Related Disorders, Myositis, Scleroderma and Vasculitis

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Genome-wide association studies have identified nearly 60 susceptibility loci for systemic lupus erythematosus (SLE). However, few studies have investigated their influence on specific disease manifestations. Antiphospholipid antibodies (aPL) are present in 30-40% of those with SLE and are major risk factors for thrombosis in childhood-onset SLE (cSLE). We hypothesized that SLE susceptibility loci are also associated with antiphospholipid antibody-positivity in cSLE.

Methods: We tested 41 SLE-related single nucleotide polymorphisms (SNPs) for association with lupus anticoagulant (LA) positivity and the presence of anti-cardiolipin (aCL) antibodies among cSLE patients diagnosed and followed at the Hospital for Sick Children, Toronto. Participants were genotyped on the Illumina Immunochip. Untyped SNPs were imputed from a 1000 genomes reference panel. Associations between SNPs and antibody status (positive/negative) were tested individually under the additive model and in a weighted genetic risk score.

Results: Among our sample of 348 cSLE patients, 56 were positive for LA and 144 were aCL-positive. The median age of SLE diagnosis was 13 (interquartile range: 11 – 15) and 19% were male. Of the 41 SNPs tested, 38 were genotyped or imputed with high quality. A one unit increase in SLE genetic risk score was associated with a 20% increase in odds of LA positivity (odds ratio (OR) 1.20; 95% CI: 0.88, 1.64) and a 13% increased odds of aCL (OR 1.13, 95% CI: 0.90 – 1.44) after adjustment for sex, age of SLE onset and ancestry. Though few were statistically significant, suggestive associations with antibody status were also seen for several of the individual SNPs included in the genetic risk score.

Conclusion: Our findings suggest that specific genetic variants related to SLE onset may underlie the development of aPL in cSLE patients.

Disclosure: L. T. Hiraki, None; F. Gagnon, None; E. Silverman, None; D. M. Levy, None; S. Abu Alsaoud, None; K. Everett, None.

To cite this abstract in AMA style:

Hiraki LT, Gagnon F, Silverman E, Levy DM, Abu Alsaoud S, Everett K. Associations between Systemic Lupus Susceptibility (SLE) Loci and Anti-Phospholipid Antibody (aPL) Positivity in Childhood-Onset SLE (cSLE) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/associations-between-systemic-lupus-susceptibility-sle-loci-and-anti-phospholipid-antibody-apl-positivity-in-childhood-onset-sle-csle/. Accessed .

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