Autoantigens Identified by Screening a Human Heart cDNA Library with Acute Rheumatic Fever Sera

• Published in: Annals of the New York Academy of Sciences 2009-09, Vol.1173 (1), p.83-91
• Main Authors: Towers, Rebecca J., Bolm, Maike, Currie, Bart J., Chhatwal, Gursharan S., Fagan, Peter K.
• Format: Article
• Language: English
• Subjects: Acute Disease; acute rheumatic fever; Adult; alpha Catenin - immunology; alpha Catenin - metabolism; Antigens; Australia; Australian indigenous communities; autoantigen; Autoantigens - immunology; Carrier Proteins - immunology; Carrier Proteins - metabolism; DNA, Complementary - genetics; DNA, Complementary - immunology; Enzyme-Linked Immunosorbent Assay - methods; Escherichia coli - genetics; Fever; Gene Library; Group A streptococcus; Heart valves; Human; human heart cDNA expression library; Humans; Immunoglobulin Heavy Chains - immunology; Immunoglobulin Heavy Chains - metabolism; Libraries; Mediator Complex; Microfilament Proteins - immunology; Microfilament Proteins - metabolism; Middle Aged; Myocardium - metabolism; Myosin Light Chains - immunology; Myosin Light Chains - metabolism; Nerve Tissue Proteins - immunology; Nerve Tissue Proteins - metabolism; Nuclear Proteins - immunology; Nuclear Proteins - metabolism; Patients; Proteins; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; Rheumatic Fever - blood; Rheumatic Fever - diagnosis; Rheumatic Fever - immunology; Streptococcus; Transcription Factors - immunology; Transcription Factors - metabolism
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2009.04653.x

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.