Influence of Host Genetics on the Severity of Coccidioidomycosis

Coccidioidomycosis, a mild flulike illness in approximately 40% of infected persons, progresses to severe pulmonary or disseminated disease in 1% to 10% of symptomatic cases. We examined host genetic influences on disease severity among class II HLA loci and the ABO blood group. Participants included African-American, Caucasian, and Hispanic persons with mild or severe disseminated coccidioidomycosis from Kern County, California. Among Hispanics, predisposition to symptomatic disease and severe disseminated disease is associated with blood types A and B, respectively. The HLA class II DRB1*1301 allele marks a pre-disposition to severe disseminated disease in each of the three groups. Reduced risk for severe disease is associated with DRB1*0301-DQB1*0201 among Caucasians and Hispanics and with DRB1*1501-DQB1*0602 among African-Americans. These data support the hypothesis that host genes, in particular HLA class II and the ABO blood group, influence susceptibility to severe coccidioidomycosis.