Sex differences in concentrations of HMGB1 and numbers of pigmented monocytes in infants with malaria

Females generally mount more robust innate and adaptive immune responses and demonstrate a higher rate of morbidity, and prevalence of autoimmune diseases by comparison with males. In malaria, females demonstrate higher concentrations of antibodies and rates of severe adverse events and mortality following natural infections and malaria vaccination. Although monocytes/macrophages play a crucial role in disease and protection in malaria, no studies have investigated sex differences in their functions in production of proinflammatory cytokines and chemokines in malaria-infected subjects. Here, we show significant sex differences in serum concentrations of HMGB1, a non-histone chromatin-associated protein, and numbers of pigmented monocytes, which are both markers of severe malaria, in infants <5 years old from a malaria endemic region in Northern Uganda. Female infants with clinical malaria had significantly higher HMGB1 concentrations than male infants, and female infants with asymptomatic malaria had significantly lower numbers of pigmented monocytes than male infants with asymptomatic malaria. There was (1) a significant correlation between HMGB1 concentrations and pigmented monocyte numbers in female but not male infants; and (2) a significant correlation between HMGB1 concentrations and parasite densities in female but not male infants. These findings suggest that female infants with clinical malaria might be at a greater risk of morbidity characterized by higher serum HMGB1 levels.