ACR open rheumatology · 2026
HLA-B Associates With Distinct Disease Expression in Juvenile Spondyloarthritis: A Retrospective Cohort Study.
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Bikas Dimitrios V, Brandon Timothy G, Newby Brittney N, Weiss Pamela F
Аннотация
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.
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.