What are the Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of Human Leukocyte Antigen (HLA) B51 in Behçet's disease?

HLA-B51 in Behçet's Disease: PPV and NPV Analysis

HLA-B51 has a moderate positive predictive value (PPV) of approximately 55% and a high negative predictive value (NPV) of around 84-90% for Behçet's disease, making it more useful for excluding the disease than confirming it. 1, 2

Prevalence and Geographic Distribution of HLA-B51

• HLA-B51 prevalence varies significantly by ethnicity, ranging from <1% in some African populations to 10-15% in Han Chinese populations 2
• In Caucasian populations, HLA-B51 prevalence is approximately 5-8% 2
• In African American populations, prevalence is approximately 2.5% 2
• This variation in prevalence directly impacts the predictive values of HLA-B51 testing in different populations 1

Diagnostic Value in Behçet's Disease

Positive Predictive Value (PPV)

• The PPV of HLA-B51 for Behçet's disease is approximately 55% 1
• This moderate PPV indicates that many HLA-B51 positive individuals will not develop Behçet's disease 3
• PPV varies significantly based on the prevalence of Behçet's disease in the tested population, being higher in regions with greater disease prevalence like Turkey and lower in regions with lower prevalence 4

Negative Predictive Value (NPV)

• The NPV of HLA-B51 for Behçet's disease is approximately 84-90% 1
• This high NPV makes HLA-B51 testing more valuable for excluding Behçet's disease than for confirming it 3
• A negative HLA-B51 test substantially reduces the likelihood of Behçet's disease, though it does not completely rule it out 5

Clinical Implications and Recommendations

• HLA-B51 testing should not be used as a standalone diagnostic test for Behçet's disease but rather as supportive evidence 1
• HLA-B51 positivity is associated with specific clinical manifestations, particularly ocular lesions (OR 1.59) 4
• HLA-B51 negative patients have higher risk for genital ulceration (OR 0.72) and gastrointestinal symptoms (OR 0.65) 4
• The International Criteria for Behçet's Disease (ICBD) does not include HLA-B51 in its primary diagnostic criteria, reflecting its limited diagnostic specificity 4
• HLA-B51 testing may be most useful in cases with incomplete clinical presentation to help rule out Behçet's disease when negative 3, 6

Prognostic Value

• HLA-B51 positivity may indicate a more severe disease course, particularly for ocular involvement 5
• In Egyptian patients, HLA-B*51:08 was significantly associated with legal blindness (OR = 2.98) 5
• Other HLA alleles may provide additional prognostic information; for example, HLA-B*27 has been associated with more severe disease in Portuguese patients 6
• The presence of HLA-Bw4-80I epitope (present on HLA-B*51 and other B-locus molecules) shows significant association with Behçet's disease, suggesting a potential pathogenic mechanism 7

Limitations and Caveats

• The predictive values of HLA-B51 testing vary significantly based on the ethnicity of the tested population and the local prevalence of Behçet's disease 2, 4
• Other genetic factors, including HLA-A26, HLA-Cw16, and HLA-Bw4-80I, may contribute to disease susceptibility independently of HLA-B51 6, 7
• Testing methodology and quality can affect the accuracy of HLA typing results 1
• The clinical utility of HLA-B51 testing must be interpreted in the context of the complete clinical presentation 1

Practical Application

• Consider HLA-B51 testing as part of the diagnostic workup for suspected Behçet's disease, particularly in patients with incomplete clinical presentation 1, 3
• A negative HLA-B51 result should increase confidence in excluding Behçet's disease, especially when clinical features are equivocal 1
• A positive HLA-B51 result should prompt closer monitoring for ocular complications 4, 5
• In HLA-B51 positive patients with Behçet's disease, more aggressive treatment and monitoring may be warranted due to potentially higher risk of severe ocular disease 5