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HLA-B Associates With Distinct Disease Expression in Juvenile Spondyloarthritis: A Retrospective Cohort Study
Dimitrios V Bikas1, Timothy G Brandon1,2, Brittney N Newby1
1Department of Pediatrics, Division of Rheumatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Insights
Specific HLA-B genotypes are linked to distinct disease presentations in children with juvenile spondyloarthritis (JSpA). This finding suggests HLA-B variants play a role in JSpA
Area of Science:
- Immunogenetics
- Pediatric Rheumatology
- Genomic Medicine
Background:
- Juvenile spondyloarthritis (JSpA) encompasses several subtypes of chronic inflammatory arthritis in children.
- The human leukocyte antigen B (HLA-B) gene is known to be associated with various autoimmune and inflammatory conditions.
- Understanding the genetic underpinnings of JSpA is crucial for improving diagnosis and treatment.
Purpose of the Study:
- To investigate the association between specific HLA-B genotypes and the clinical phenotype of JSpA in pediatric patients.
- To explore how different HLA-B variants correlate with distinct JSpA subtypes, including enthesitis-related arthritis (ERA), psoriatic arthritis (PsA), and inflammatory bowel disease-associated arthritis (IBD-AA).
Main Methods:
- A cross-sectional retrospective study involving 150 children diagnosed with JSpA subtypes or related conditions.
- Comprehensive HLA-B genotyping was performed on all participants.
- HLA-B allele frequencies in the JSpA cohort were compared to a national cohort, with statistical analysis adjusted for multiple testing.
Main Results:
- Twenty-eight percent of JSpA patients were positive for HLA-B*27.
- The HLA-B*35:02 variant was significantly more common in children with inflammatory bowel disease-associated arthritis (IBD-AA) and overall inflammatory bowel disease (IBD).
- The HLA-B*57:01 variant showed a significant enrichment in children diagnosed with psoriatic arthritis (PsA).
Conclusions:
- Specific HLA-B variants are associated with distinct disease phenotypes in JSpA, suggesting a role in disease pathogenesis.
- These findings highlight the importance of immunogenetic factors, particularly HLA-B, in the diverse clinical expression of JSpA.
- Further research into the biological mechanisms linking HLA-B and JSpA is warranted to inform clinical care and future therapeutic strategies.
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.
