Population genetics and external proficiency testing for HLA disease associations

Area of Science:

• Immunogenetics
• Clinical Diagnostics
• Population Genetics

Background:

• Numerous Human Leukocyte Antigen (HLA) variants are associated with disease susceptibility, particularly those with immunopathological components.
• Strongest HLA associations are integrated into diagnostic algorithms, with disease-associated variants detected via DNA-based assays.
• Specialized diagnostic tests for specific HLA markers and complete typing for HLA loci are available.

Purpose of the Study:

• To review and discuss selected aspects of external proficiency testing (EPT) for HLA disease associations.
• To emphasize the role of population genetics in optimizing HLA testing for disease associations.
• To guide laboratories, diagnostic producers, and EPT providers in enhancing the diagnostic value of HLA tests.

Main Methods:

• Review of selected aspects of external proficiency testing (EPT) for HLA disease associations.
• Discussion focused on population genetics, HLA typing resolution, allele distribution, and linkage disequilibrium.
• Analysis of interpretation of common and less common HLA variants/haplotypes.

Main Results:

• EPT supports accurate technical identification and clinical interpretation of disease-associated HLA variants.
• Population-based differences in HLA alleles and their distribution impact diagnostic value.
• Optimal HLA typing resolution and consideration of population genetics are key for accurate diagnostics.

Conclusions:

• Laboratories, diagnostic producers, and EPT providers must consider population genetic characteristics to optimize diagnostic tests for disease-associated HLA variants.
• Effective EPT enhances the reliability of HLA testing in clinical practice.
• Integrating population genetics into HLA testing improves diagnostic accuracy and clinical utility.