Poster Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Identifying Autoantibody Targets as New Biomarkers for Acute Rheumatic Fever using Mass Spectrometry and High Content Protein Arrays (#180)

Mei Lin Tay 1 , Paulina Hanson-Manful 1 , Jeremy Raynes 1 , Nicole (Nikki) Moreland 1 , Rheumatic Fever Risk Factor Study Group
  1. Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand

Acute rheumatic fever (ARF) and associated rheumatic heart disease (RHD) are serious sequelae of Group A Streptococcus (GAS) infection. Rates of ARF/RHD remain unacceptably high in the developing world and in indigenous populations in certain developed counties such as Australia and New Zealand. Specific diagnostic tests for ARF are lacking, with diagnosis instead relying on a set of clinical criteria. This presents a major hurdle in disease control efforts, with an accurate diagnosis requiring a series of assessments over a period of days. Our aim is to identify novel human targets of auto-antibodies in patients with ARF that can serve as biomarkers for diagnosis. Firstly, an optimised western blot protocol has been developed to test for heart reactive antibodies from the sera of ARF patients with carditis. Reactivity of ARF sera was screened in whole heart lysates, as well as aorta and mitral valve lysates. Specific bands detected in ARF sera and not healthy control sera have been subject to mass spectrometry for identification. Secondly, high content array technology has been applied to identify potential autoantibody targets in an unbiased fashion. Arrays containing 9000 (Protoarray) and 15000 (HuProt Array) human proteins have been screened with ARF patient sera (with and without carditis) and matched healthy controls. Analysis has revealed a panel of proteins that have potential as biomarkers in ARF. Validation of these potential hits in immunoassays with larger patient numbers will be presented as a route to assessing the utility of the proteins in clinical diagnosis of ARF.