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Susceptibility to Acute Rheumatic Fever Based on Differential Expression of Genes Involved in Cytotoxicity, Chemotaxis, and Apoptosis

Bryant, Penelope A., Smyth, Gordon K., Gooding, Travis, Oshlack, Alicia, Harrington, Zinta, Currie, Bart J., Carapetis, Jonathan R., Robins-Browne, Roy and Curtis, Nigel (2014). Susceptibility to Acute Rheumatic Fever Based on Differential Expression of Genes Involved in Cytotoxicity, Chemotaxis, and Apoptosis. Infection and Immunity,82(2):753-761.

Document type: Journal Article
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IRMA ID 11436xPUB12
Title Susceptibility to Acute Rheumatic Fever Based on Differential Expression of Genes Involved in Cytotoxicity, Chemotaxis, and Apoptosis
Author Bryant, Penelope A.
Smyth, Gordon K.
Gooding, Travis
Oshlack, Alicia
Harrington, Zinta
Currie, Bart J.
Carapetis, Jonathan R.
Robins-Browne, Roy
Curtis, Nigel
Journal Name Infection and Immunity
Publication Date 2014
Volume Number 82
Issue Number 2
ISSN 0019-9567   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-84893020280
Start Page 753
End Page 761
Total Pages 9
Place of Publication United States of America
Publisher American Society for Microbiology
HERDC Category C1 - Journal Article (DIISR)
Abstract 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.
DOI http://dx.doi.org/doi:10.1128/IAI.01152-13   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Description for Link Link to publisher's version
URL http://iai.asm.org/content/82/2/753
 
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