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Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
Plasma complement and vascular complement deposition in patients with coronary artery disease with and without
Kelly J Shields1, Tom Eirik Mollnes2,3,4, Jon Roger Eidet5
1Lupus Center of Excellence, Autoimmunity Institute, Department of Medicine, Allegheny Health Network, Pittsburgh, Pennsylvania, United States of America.
Insights
Inflammatory rheumatic diseases (IRD) accelerate coronary artery disease (CAD) through complement activation. Complement activation products like C3d in aortic tissue indicate this link, suggesting new therapeutic targets for cardiovascular disease (CVD).
Area of Science:
- Cardiovascular Medicine
- Rheumatology
- Immunology
Background:
- Inflammatory rheumatic diseases (IRD) are linked to accelerated coronary artery disease (CAD).
- The complement system may play a role in CAD pathogenesis in conditions like Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA).
Purpose of the Study:
- To investigate the association between circulating complement and its activation products with vascular inflammation markers in IRD patients with CAD.
- To compare complement activation product deposition in aortic biopsies from patients with and without IRD, including SLE and RA.
Main Methods:
- Plasma levels of C3 and terminal complement complexes (TCC) were measured in IRD patients with CAD, non-IRD patients with CAD, and IRD patients without CAD.
- Aortic biopsies were analyzed for mononuclear cell infiltrates (MCI) and complement components (C3, C3d) using immunohistochemistry.
Main Results:
- Patients with IRD and CAD exhibited higher plasma TCC levels compared to other groups.
- Inflammatory rheumatic disease status was independently associated with the presence and size of MCI in the aorta.
- C3d deposition was found in the aortic media of all patients and in the adventitia of IRD patients, particularly those with SLE.
Conclusions:
- The findings support a distinct relationship between rheumatic diseases, especially SLE, and the complement system in the context of cardiovascular disease.
- Elevated systemic and vascular complement activation may contribute to accelerated cardiovascular disease (CVD) and could serve as a biomarker or therapeutic target.
Purpose:
Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients.
Methods:
We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry.
Results:
IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (p<0.0001), but a similar p-C3 level (p = 0.42). Circulating C3 was associated with IRD duration (ρ, p-value: 0.46, 0.03). In multiple logistic regression analysis, IRD remained significantly related to the presence and size of MCI (p<0.05). C3 was present in all tissue samples. C3d was detected in the media of all patients and only in the adventitia of IRD patients (diffuse in all SLE and focal in one RA).
Conclusion:
The independent association of IRD status with MCI and the observed C3d deposition supports the unique relationship between rheumatic disease, and, in particular, SLE with the complement system. Exaggerated systemic and vascular complement activation may accelerate CVD, serve as a CVD biomarker, and represent a target for new therapies.
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