HLA
‐B Associates With Distinct Disease Expression in Juvenile Spondyloarthritis: A Retrospective Cohort Study
Dimitrios V. Bikas, Timothy G. Brandon, Brittney N. Newby, Pamela F. Weiss Objective
This study aimed to investigate for possible association between HLA‐B genotype and disease phenotype in children with juvenile spondyloarthritis (JSpA).
Methods
This was a cross‐sectional retrospective study of children evaluated at a large tertiary care rheumatology clinic. Inclusion criteria were (1) fulfillment of criteria for juvenile idiopathic arthritis (JIA) subtypes: enthesitis‐related arthritis (ERA), psoriatic arthritis (PsA), or undifferentiated JIA (ERA criteria plus a first‐degree relative with psoriasis); or (2) a diagnosis of inflammatory bowel disease‐associated arthritis (IBD‐AA); or (3) magnetic resonance imaging‐confirmed inflammatory sacroiliitis in patients who did not meet JIA subtype criteria. All children underwent complete HLA‐B testing. Comparisons of HLA‐B allele frequencies between JSpA and a published national cohort were conducted through two‐sample tests of proportions and controlled for multiple testing using the Benjamini–Hochberg procedure.
Results
There were 150 children who met the inclusion criteria, and 28% (42 of 150) were HLA‐B*27 ‐positive. Overall, participants exhibited pronounced heterogeneity in phenotypic and allelic composition, with HLA‐B variants associated with distinct patterns of disease expression. Overall, HLA‐B*35:02 was significantly enriched in children with IBD‐AA ( P = 0.007) and in the overall occurrence of IBD ( P = 0.005), whereas HLA‐B*57:01 was significantly enriched in children with PsA ( P = 0.006).
Conclusion
These patterns suggest a key role for HLA‐B variants in disease pathogenesis, possibly driving diverse JSpA expression through distinct immunogenetic dysregulation. Our findings underscore the need to further elucidate the biologic connection between HLA‐B and JSpA, with potential insights that may inform clinical care and guide future investigation.