Background/Purpose: Behçet’s disease (BD) is a chronic systemic disease with heterogenous clinical presentations. The strongest genetic risk factor and diagnostic biomarker for BD is the class I major histocompatibility complex antigen HLA-B51. Although best studied in ‘Silk-Road’ populations, B51’s prevalence in BD varies considerably across different racial/ethnic groups (Capittini, et al. Dis Markers, 2021). The genetic risks in American populations with BD are limited. This study describes the associations between HLA-B alleles and demographics in a diverse BD population from a large urban academic medical center in Los Angeles County.

Methods: Inclusion criteria required that patients had HLA-B allele testing (by sequence-specific oligonucleotide-polymerase chain reaction typing) conducted in routine clinical care, and were identified as having BD with >2 ICD-9/10 codes for BD. A sensitivity analysis with a more restrictive cohort (>2 ICD-9/10 codes for BD, plus >1 rheumatology encounter, plus >1 DMARD prescription) was performed, and had similar demographic/genetic features. HLA-B alleles evaluated in the analysis included known relevant alleles (B51, B27), and the other 3 alleles of highest frequency.

Results: There were 144 identified BD patients, with B51 positivity in 33% (48 patients), versus a B51 prevalence of 11% among 2614 non-rheumatic controls (p< 0.0001). Amongst the BD patients, the alleles of highest frequency were B51 (49), B7 (31), B44 (28), and B35 (25) (Figure 1). Comparing B51(+) versus B51(-) BD patients, the groups were similar by age, gender, race/ethnicity and use of disease modifying agents (Table 1). However, there were higher percentages of B7(+) and B44(+) patients in the B51(-) group (Table 1). 35% of BD patients identified as white and compared to non-white BD patients had similar rates of B51(+), but a higher rate of B27(+) (16% vs 4%, p=0.01). White BD patients compared to white non-rheumatic controls had significantly higher B51(+) and B27(+). Non-white/Hispanic BD patients compared to non-white/Hispanic controls had significantly higher B51(+). The unadjusted odds ratios (OR) for BD (yes/no) demonstrated B51(+) 4.13 (95% CI 2.92, 5.85), female gender 3.5 (2.35, 5.30), and Hispanic ethnicity 0.48 (0.29, 0.77) (Figure 2). B51, gender, and Hispanic ethnicity remained significant in a multivariate model, and interaction terms were non-significant.

Conclusion: In a large diverse U.S. urban academic medical center, BD was significantly associated with B51(+) and was present in ~1/3 of BD patients. B51(+) did not differ significantly between race or ethnicity. White BD patients had significantly higher rates of B27(+) than non-rheumatic white controls, and non-white BD patients. This data shows that U.S. BD patients may have lower B51(+), and higher female prevalence than in Silk-Road BD populations, which may reflect different genetic/environmental risks for BD. Limitations include selection bias (patients had to have clinically indicated HLA-B allele testing), and misclassification bias utilizing ICD codes (though sensitivity analysis demonstrated similar baseline/genetic features).

Values represent HLA-B allele count from total of 285 alleles (144 Behçet’s patients, 3 missing copies). Excluded the following HLA-B alleles representing < 3% prevalence, but still present at least once: HLA-B: 13, 37, 38, 39, 41, 42, 45, 46, 47, 48, 49, 50, 55, 56, 57, 58, 61, 63, 65, 67, 71, 72, 75, 77.

Values represent n (%) for categorical variables, and mean (SD) for continuous variables.

Race, ethnicity, and gender are self-reported by the patient.

*p < 0.05, by Chi-Squared testing comparing B51(+) vs (-)

AAPI=Asian American/Pacific Islander, DMARD=disease modifying anti-rheumatic drug, csDMARD=conventional synthetic DMARD, bDMARD=biologic DMARD (RA=bDMARDs for RA, SpA=bDMARDs for spondyloarthritis, including IL17i, IL12/23i, IL23i), tsDMARD=targeted synthetic DMARD.

Univariate logistic regressions for the outcome of Behçet’s Disease diagnosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/behcets-disease-in-a-diverse-urban-single-center-cohort-in-the-united-states-hla-b-alleles-and-clinical-features/