Abstract
Purpose :
Paediatric uveitis is a potentially blinding disease. To date, the aetiology of childhood uveitis is poorly understood. Genome-wide association studies have linked peptide motifs in HLA molecules to susceptibility of paediatric uveitis. Our aim was to comprehensively map the association of HLA alleles with childhood uveitis.
Methods :
Whole gene next generation sequencing of all classical HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci was performed in 280 children with different forms of uveitis. Dense genotype data from 499 Dutch controls from Genome of The Netherlands were imputed using the SNP2HLA pipeline, using 5,225 samples from European-ancestry from the Type 1 Diabetes Genetics Consortium as reference panel. Cases and controls were compared using logistic regression models adjusting for sex.
Results :
In total, 179 unique classical alleles were determined at second field resolution or higher. For cases with juvenile idiopathic arthritis associated uveitis, we ascertained the strong association to HLA-DRB1*08:01 (OR = 11.12, 95% CI 5.76-21.43; P = 6.51 × 10-13) and HLA-DQB1*04:02 (OR = 10.11, 95% CI 5.32-19.22; P = 1.69 × 10-12). There was no HLA-wide significant association signal for intermediate uveitis (lead allele, HLA-DRB1*15:01; OR = 2.18, 95% CI 1.26-3.77; P = 0.005). In contrast, we detected HLA-DRB1*01:02 (OR = 9.98, 95% CI 4.47-22.28; P =1.9 × 10-8) as the primary association in patients with panuveitis. No unique HLA amino acid polymorphisms were associated with the different forms of uveitis.
Conclusions :
These findings suggest distinct genetic susceptibility in paediatric uveitis and might help classifying different forms of uveitis in the future.
This is a 2021 ARVO Annual Meeting abstract.