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Updated: Jun 15, 2025
Generation of Two-color Antigen Microarrays for the Simultaneous Detection of IgG and IgM Autoantibodies
Published on: September 15, 2016
An acute rheumatic fever immune signature comprising inflammatory markers, IgG3, and Streptococcus pyogenes-specific
Natalie Lorenz1,2, Reuben McGregor1,2, Alana L Whitcombe1,2
1School of Medical Science, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Abstract:
Understanding the immune profile of acute rheumatic fever (ARF), a serious post-infectious sequelae of Streptococcal pyogenes (group A Streptococcus [GAS]), could inform disease pathogenesis and management. Circulating cytokines, immunoglobulins, and complement were analyzed in participants with first-episode ARF, swab-positive GAS pharyngitis and matched healthy controls. A striking elevation of total IgG3 was observed in ARF (90% > clinical reference range for normal). ARF was also associated with an inflammatory triad with significant correlations between interleukin-6, C-reactive protein, and complement C4 absent in controls. Quantification of GAS-specific antibody responses revealed that subclass polarization was remarkably consistent across the disease spectrum; conserved protein antigens polarized to IgG1, while M-protein responses polarized to IgG3 in all groups. However, the magnitude of responses was significantly higher in ARF. Taken together, these findings emphasize the association of exaggerated GAS antibody responses, IgG3, and inflammatory cytokines in ARF and suggest IgG3 testing could beneficially augment clinical diagnosis.
Insights
Acute rheumatic fever (ARF) is linked to heightened group A Streptococcus (GAS) antibody responses, particularly IgG3. This immune profile, including inflammatory cytokines, may aid in ARF diagnosis and understanding its pathogenesis.
Area of Science:
- Immunology
- Infectious Diseases
- Rheumatology
Background:
- Acute rheumatic fever (ARF) is a significant post-infectious complication of group A Streptococcus (GAS) infection.
- Understanding the immune mechanisms of ARF is crucial for improving disease management and pathogenesis insights.
Purpose of the Study:
- To characterize the circulating immune profile in patients with first-episode ARF.
- To compare immune responses in ARF, GAS pharyngitis, and healthy controls.
- To investigate the role of specific antibody subclasses and inflammatory markers in ARF.
Main Methods:
- Analysis of circulating cytokines, immunoglobulins (including IgG subclasses), and complement components.
- Quantification of GAS-specific antibody responses.
- Comparison between patients with ARF, GAS pharyngitis, and healthy controls.
Main Results:
- Elevated total IgG3 levels were observed in 90% of ARF patients.
- ARF was associated with an inflammatory triad (interleukin-6, C-reactive protein, complement C4).
- GAS-specific antibody responses, particularly IgG3 to M-protein, were significantly higher in ARF patients.
Conclusions:
- Exaggerated group A Streptococcus antibody responses, specifically IgG3, and inflammatory cytokines are associated with ARF.
- IgG3 testing may serve as a valuable adjunct for clinical diagnosis of ARF.
- Immune profiling provides insights into ARF pathogenesis.
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