Journal article

Systems immunology reveals a linked IgG3-C4 response in patients with acute rheumatic fever

Amy W Chung, Timothy KC Ho, Paulina Hanson-Manful, Susanne Tritscheller, Jeremy M Raynes, Alana L Whitcombe, Mei Lin Tay, Reuben McGregor, Natalie Lorenz, Jane R Oliver, Jason K Gurney, Cristin G Print, Nigel J Wilson, William J Martin, Deborah A Williamson, Michael G Baker, Nicole J Moreland



Acute rheumatic fever (ARF) and chronic rheumatic heart disease (RHD) are autoimmune sequelae of a Group A streptococcal infection with significant global mortality and poorly understood pathogenesis. Immunoglobulin and complement deposition were observed in ARF/RHD valve tissue over 50 years ago, yet contemporary investigations have been lacking. This study applied systems immunology to investigate the relationships between the complement system and immunoglobulin in ARF. Patients were stratified by C-reactive protein (CRP) concentration into high (≥10 μg mL-1 ) and low (<10 μg mL-1 ) groups to distinguish those with clinically significant inflammatory processes from those with abating infl..

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Funding Acknowledgements

This work was funded by the Maurice Wilkins Centre for Biodiscovery and a Heart Foundation of New Zealand Senior fellowship to NJM. The Rheumatic Fever Risk Factors study, from which samples were obtained, was funded by the Heath Research Council of New Zealand (HRC) Rheumatic Fever Research Partnership (Ministry of Health, Te Puni Kokiri, Cure Kids, Heart Foundation, and HRC). We thank staff in pediatric departments across the North Island of New Zealand for kind support and assistance. All members of the Rheumatic Fever Risk Factors Study (in addition to the authors on this manuscript) are gratefully acknowledged.