Abstract
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.