Autoantigens identified by screening a human heart cDNA library with acute rheumatic fever sera.
Acute rheumatic fever (ARF) is an autoimmune sequela of group A streptococcal infection mostly affecting school-aged children. Recurrent episodes of ARF can result in the development of rheumatic heart disease (RHD). One in 40 indigenous Australians in the Northern Territory is affected by RHD. This disease mostly impacts young people; 45% of those who require heart valve surgery in Australia due to RHD are younger than 25 years old. ARF is characterized by autoimmune attack of the heart; therefore, the presence of the autoantibodies involved could potentially be used to diagnose ARF. To this end, a human heart cDNA library was screened with serum from a patient with ARF, and 12 autoreactive human heart antigens were identified. They include five different IgG heavy chains and a range of tissue-specific cell-signaling proteins, species of which have been implicated in other autoimmune diseases. Preliminary ELISA results show that ARF patients have significantly higher levels of antibodies recognizing the cardiac autoantigens than controls. These antigens are promising candidates for the development of a serological assay for the diagnosis of ARF. The nature of the proteins identified has exciting implications for future research into the pathogenesis of ARF.
Towers
Rebecca J
RJ
Tropical and Emerging Infectious Diseases Division, Menzies School of Health Research, Darwin, Australia. rebecca.towers@menzies.edu.au
Bolm
Maike
M
Currie
Bart J
BJ
Chhatwal
Gursharan S
GS
Fagan
Peter K
PK
D000208:Acute Disease; D000328:Adult; D001324:Autoantigens / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D018797:Cell Cycle Proteins; D018076:DNA, Complementary / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004926:Escherichia coli / Q000235:genetics; D015723:Gene Library; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology / Q000378:metabolism; D056892:Mediator Complex; D008840:Microfilament Proteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D018994:Myosin Light Chains / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D012213:Rheumatic Fever / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism; D051178:alpha Catenin / Q000276:immunology / Q000378:metabolism
D001324:Autoantigens; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D007143:Immunoglobulin Heavy Chains; C491863:MED4 protein, human; D056892:Mediator Complex; D008840:Microfilament Proteins; D018994:Myosin Light Chains; C501659:NEXN protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; C490381:SMC2 protein, human; C485904:SYNE2 protein, human; D014157:Transcription Factors; D051178:alpha Catenin