1Department of Anthropology, University of Louisville, 2Department of Pathology and Laboratory Medicine, University of Louisville
Saturday 2:45-3:00, Ballroom B
The polymorphic nature of many immune genes often influences the serum levels of the immune proteins themselves. During the last two decades, the amount of data on immune gene polymorphisms (IGP) has increased dramatically, with a growing number of studies suggesting an effect of those polymorphisms on immune disease susceptibility. However many studies have failed to show significant association between IGP and particular diseases. We proposed that the existence of high levels of phenotypic plasticity (PP) should be considered before making any conclusions when linking IGP, the corresponding protein expression, and disease susceptibility. To address the hypothesis of high levels of PP, we conducted an in vitro study on human peripheral blood mononuclear cells (PBMC) from healthy donors (n=25, Caucasians), testing the effects of pathogenic antigens on the expression phenotypes for different cytokines when cytokine genetic information is taken into consideration. The cytokine polymorphisms analyzed were: TNFα (-308A/G); TGFβ1 (codon 10T/C, codon 25C/G); IL-10 ( -1082 A/G, -819T/C, -592A/C); IL-6 (-174C/G); and IFNγ (+874 T/A). PBMC were stimulated in vitro, with either lipoarabinomannan-LAM (lipopolysaccharide from Mycobacterium wall) or lipopolysaccharide-LPS (general proxy for bacterial infection). Cytokine expression was measured by ELISA and Luminex technology. Preliminary results show that despite similar genotypic backgrounds for some cytokine polymorphisms, cytokine production varied among donors and sex, suggesting significant PP among humans when exposed to the same pathogenic antigens. We suggest that this plasticity is the legacy of differential exposure to and co-evolution with infectious diseases over the course of human evolution.