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

Show simple item record Chung, Amy W Ho, Timothy Kc Hanson-Manful, Paulina Tritscheller, Susanne Raynes, Jeremy M Whitcombe, Alana L Tay, Mei Lin McGregor, Reuben Lorenz, Natalie Oliver, Jane R Gurney, Jason K Print, Cristin G Wilson, Nigel J Martin, William J Williamson, Deborah A Baker, Michael G Moreland, Nicole J 2020-12-08T01:32:43Z 2020-12-08T01:32:43Z 2020-1
dc.identifier.issn 1440-1711
dc.description.abstract 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 inflammation. The circulating concentrations of 17 complement factors and six immunoglobulin isotypes and subclasses were measured in ARF patients and highly matched healthy controls using multiplex bead-based immunoassays. An integrative statistical approach combining feature selection and principal component analysis revealed a linked IgG3-C4 response in ARF patients with high CRP that was absent in controls. Strikingly, both IgG3 and C4 were elevated above clinical reference ranges, suggesting these features are a marker of ARF-associated inflammation. Humoral immunity in response to M protein, an antigen implicated in ARF pathogenesis, was completely polarized to IgG3 in the patient group. Furthermore, the anti-M-protein IgG3 response was correlated with circulating IgG3 concentration, highlighting a potential role for this potent immunoglobulin subclass in disease. In conclusion, a linked IgG3-C4 response appears important in the initial, inflammatory stage of ARF and may have immediate utility as a clinical biomarker given the lack of specific diagnostic tests currently available.
dc.format.medium Print-Electronic
dc.language eng
dc.publisher Wiley
dc.relation.ispartofseries Immunology and cell biology
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
dc.subject Humans
dc.subject Rheumatic Fever
dc.subject Immunoglobulin G
dc.subject Adolescent
dc.subject Child
dc.subject Complement C4
dc.subject Female
dc.subject Male
dc.subject Immunity, Humoral
dc.subject Science & Technology
dc.subject Life Sciences & Biomedicine
dc.subject Cell Biology
dc.subject Immunology
dc.subject C4
dc.subject complement
dc.subject IgG3
dc.subject immunoglobulin
dc.subject M protein
dc.subject rheumatic fever
dc.subject HEART-DISEASE
dc.subject COMPLEMENT
dc.subject IMMUNITY
dc.subject ANTIBODIES
dc.subject CHILDREN
dc.subject 1102 Cardiorespiratory Medicine and Haematology
dc.subject Clinical Medicine and Science
dc.subject Autoimmune Disease
dc.subject Cardiovascular
dc.subject Heart Disease
dc.subject Arthritis
dc.subject Infectious Diseases
dc.subject 0601 Biochemistry and Cell Biology
dc.subject 1107 Immunology
dc.title Systems immunology reveals a linked IgG3-C4 response in patients with acute rheumatic fever.
dc.type Journal Article
dc.identifier.doi 10.1111/imcb.12298
pubs.issue 1
pubs.begin-page 12
pubs.volume 98 2020-11-08T23:20:11Z
dc.rights.holder Copyright: The author en
pubs.end-page 21
pubs.publication-status Published
dc.rights.accessrights en
pubs.subtype Clinical Trial
pubs.subtype Research Support, Non-U.S. Gov't
pubs.subtype Journal Article
pubs.elements-id 787984
dc.identifier.eissn 1440-1711 2019-11-18

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