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Complement activation in infective endocarditis: correlation with extracardiac manifestations and prognosis
I J Messias-Reason1, S Y Hayashi, R M Nisihara
1Laboratory of Immunopathology, Department of Pathology, Clinical Hospital of Federal University of Paraná, Curitiba, Brazil. immunopat@hc.ufpr.br
Insights
Infective endocarditis (IE) activates the complement system, a key part of immunity. This study found elevated complement activation products, linked to disease severity and complications, suggesting diagnostic potential for IE biomarkers.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Infectious Diseases
Background:
- Complement activation is crucial for immune response but can cause tissue damage when excessive.
- Infective endocarditis (IE) patients often have high levels of circulating immune complexes (CIC) that activate complement.
- The role of complement activation in IE's extracardiac manifestations and prognosis is not well understood.
Purpose of the Study:
- To investigate complement activation in IE patients.
- To explore correlations between complement activation products and extracardiac manifestations.
- To assess the relationship between complement activation and clinical outcomes in IE.
Main Methods:
- Plasma levels of complement activation products (C3adesArg, SC5b-9, C1rs-C1Inh, C3b(Bb)P, C3d) were measured using ELISA and immunoelectrophoresis.
- C3 and C4 levels were determined by turbidimetry.
- Circulating immune complexes (CIC) were quantified by ELISA.
Main Results:
- IE patients showed significantly elevated levels of C3d, C3adesArg, SC5b-9, and C1rs-C1Inh compared to controls, indicating classical pathway activation.
- Patients with IE had increased CIC levels and reduced C3 levels.
- Elevated C3d and C3adesArg levels correlated with pulmonary manifestations and mortality.
Conclusions:
- The classical complement pathway is activated in IE, likely mediated by CIC.
- C3d and C3adesArg show potential as biomarkers for predicting extracardiac lesions and disease severity in IE.
Abstract:
In an infectious process complement activation is necessary for a proper immune and inflammatory response, but when exacerbated may cause tissue injuries. In infective endocarditis (IE) patients tend to develop high titres of circulating immune complexes (CIC) that activate complement. The aim of this study was to evaluate for the first time complement activation in IE for possible correlation with extracardiac manifestations and clinical prognosis. Twenty patients with IE, 14 healthy controls and 15 patients presenting mitral and aortic valve lesions (with no signs of either infection or other associated diseases), were studied. Plasma levels of C3adesArg, SC5b-9, C1rs-C1Inh and C3b(Bb)P were determined by ELISA and C3d by double decker immunoelectrophoresis. C3 and C4 levels were assayed by turbidimetry and CIC by ELISA. Elevation of plasma levels of all complement activation products, with the exception of C3b(Bb)P, indicated a significant classical pathway activation in IE patients when compared to controls (C3d: P < 0.00004; C3adesArg: P < 0.03, SC5b-9: P < 0.01, C1rs-C1Inh: P < 0.00007). CIC levels were significantly increased (P < 0.005) and C3 reduced in IE patients (P < 0.05). Elevated C3d (P < 0.02) and C3adesArg (P < 0.03) levels were associated with pulmonary manifestations. In addition, C3d was significantly elevated in the patients who died when compared to those who had a good recovery (P < 0.02). Our data demonstrate the activation of the complement classical pathway, most probably mediated by CIC, in IE and suggests C3d and C3adesArg as possible markers for extracardiac lesion and severity of the disease.