Detecting HLA-infectious disease associations for multi-strain pathogens.

Human Leukocyte Antigen (HLA) molecules play a vital role helping our immune system to detect the presence of pathogens. Previous work to try and ascertain which HLA alleles offer advantages against particular pathogens has generated inconsistent results. We have constructed an epidemiological model to understand why this may occur. The model captures the epidemiology of a multi strain pathogen for which the host's ability to generate immunological memory responses to particular strains depends on that host's HLA genotype. We find that an HLA allele's ability to protect against infection, as measured in a case control study, depends on the population frequency of that HLA allele. Furthermore, our capability to detect associations between HLA alleles and infection with a multi strain pathogen may be affected by the properties of the pathogen itself (i.e R and length of infectious period). Both host and pathogen genetics must be considered in order to identify true HLA associations. However, in the absence of detailed pathogen genetic information, a negative correlation between the frequency of an HLA type and its apparent protectiveness against disease caused by multi strain pathogen is a strong indication that the HLA type in question is well adapted to a subset of strains of that pathogen.