Session Type: Abstract Submissions
Session Time: 5:30PM-7:00PM
Methods: Pediatric SLE patients and control subjects were recruited from Ohio and Atlanta, which included 105 Caucasian patients and 937 race-matched healthy subjects. The female to male ratio of pSLE was 5.7 to 1. GCNs of total C4, C4A, C4B, long and short C4 genes were determined by genomic Southern blot analyses, and/or TaqMan-based, quantitative realtime PCR using five amplicons. HLA-DRB1 variants were determined by 20 sets of specific PCR, and gel electrophoresis. Published data from 373 White aSLE were used for comparison.
Results: The copy number of total C4 genes varies from 2 to 8 copies in a diploid genome. Each of those C4 genes may code for an acidic C4A or a basic C4B protein. Low GCN of total C4 (C4T≤3) was present in 45.7% of pSLE, 42.9% of aSLE and 28.4% of healthy controls. The odds ratios and 95% confidence interval for C4T≤3 was 2.1 (1.4-3.2) in pSLE (p=0.0004), and 1.9 (1.5-2.5) in aSLE (p=4.4×10-7). Homozygous and heterozygous deficiency of C4A (C4A≤1) occurred in 39.8% of pSLE, 32.7% of aSLE, and 18.6% of healthy controls. The odds ratios for C4A deficiency were 2.9 (1.6-4.9) in pSLE (p=2.6×10-6), and 2.1 (1.6-2.8) in aSLE (p=9.9×10-8). HLA-DRB1*15 (DR2) has a frequency of 45.7% in pSLE, 31.7% in aSLE and 27.9% in controls. The odds ratios of DRB1*15 were 2.2 (1.2-4.0) for pSLE (p=0.015), but only 1.2 (0.89-1.6) for aSLE (p=0.23). Another DRB1 allele *03 (DR3) had similar frequencies in pSLE (37.0%) and aSLE (38.6%), but a significantly lower frequency in controls (26.7%). Subjects with a homozygosity of C4A deficiency, or HLA-DRB1*15, or HLA-DRB1*03 together are present in 6.0% of healthy controls, but 26.7% of pSLE [OR=5.7 (2.7-12.2), p=4×10-5] and 15.9% of aSLE [OR=3.0 (1.9-4.70), p=2.5×10-6].
Conclusion: C4A deficiency and low GCN of total C4 are significant risk factors for pediatric and adult SLE of European ancestry, but their effect sizes are consistently larger for pSLE. HLA-DRB1*15 plays an important role on the risk of pSLE. C4A deficiency, HLA-DRB1*15 and HLA-DRB1*03 have strong effects on conferring high risk of pSLE.
To cite this abstract in AMA style:Ardoin S, Avar Aydin PO, Chan LHK, Lintner K, Wu YL, Aziz R, Patwardhan A, Mulvihill E, Yu G, Zhou B, Lundstrom E, Padyukov L, Driest K, Yildirim-Toruner C, Bout-Tabaku S, Spencer C, Higgins G, Prahalad S, Brunner H, Yu CY. Deficiency of Complement C4A or Low Copy Number of Total C4 Genes, HLA-DRB1*15 and HLA-DRB1*03 Are Strong Genetic Risk Factors for Pediatric SLE of European Descent [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). https://acrabstracts.org/abstract/deficiency-of-complement-c4a-or-low-copy-number-of-total-c4-genes-hla-drb115-and-hla-drb103-are-strong-genetic-risk-factors-for-pediatric-sle-of-european-descent/. Accessed September 20, 2020.
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