Susceptibility to acute rheumatic fever based on differential expression of genes involved in cytotoxicity, chemotaxis, and apoptosis.

[acute rheumatic fever]

It is unknown why only some individuals are susceptible to acute rheumatic fever (ARF ). We investigated whether there are differences in the immune response , detectable by gene expression , between individuals who are susceptible to ARF and those who are not . Peripheral blood mononuclear cells (PBMCs ) from 15 ARF-susceptible and 10 nonsusceptible (control ) adults were stimulated with rheumatogenic (Rh +) group A streptococci (GAS ) or nonrheumatogenic (Rh-) GAS . RNA from stimulated PBMCs from each subject was cohybridized with RNA from unstimulated PBMCs on oligonucleotide arrays to compare gene expression . Thirty -four genes were significantly differentially expressed between ARF-susceptible and control groups after stimulation with Rh + GAS . A total of 982 genes were differentially expressed between Rh + GAS - and Rh- GAS -stimulated samples from ARF-susceptible individuals . Thirteen genes were differentially expressed in the same direction (predominantly decreased ) between the two study groups and between the two stimulation conditions , giving a strong indication of their involvement . Seven of these were immune response genes involved in cytotoxicity , chemotaxis , and apoptosis . There was variability in the degree of expression change between individuals . The high proportion of differentially expressed apoptotic and immune response genes supports the current model of autoimmune and cytokine dysregulation in ARF . This study also raises the possibility that a "failed " immune response , involving decreased expression of cytotoxic and apoptotic genes , contributes to the immunopathogenesis of ARF .