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Activation of classical pathway complement in chronic inflammation. Elevated levels of circulating C3d and C4d split
N E Petersen1, J Elmgreen, B Teisner
1Institute of Medical Microbiology, University of Odense, Denmark.
Insights
Complement activation, indicated by elevated split products of complement component 3 (C3d) and complement component 4 (C4d), was observed in patients with rheumatoid arthritis and Crohn's disease, suggesting classical pathway involvement.
Area of Science:
- Immunology
- Biochemistry
Background:
- The complement system plays a crucial role in innate and adaptive immunity.
- Dysregulation of complement pathways is implicated in various autoimmune and inflammatory diseases.
Purpose of the Study:
- To investigate the activation of the classical complement pathway in patients with rheumatoid arthritis (RA) and Crohn's disease (CD).
- To measure split products of complement component 3 (C3) and complement component 4 (C4) as indicators of complement activation.
Main Methods:
- Measurement of split products C3d and C4d in serum samples from untreated outpatients with RA (n=19) and CD (n=20).
- Analysis of correlations between C3d and C4d levels and assessment of native C3 and C4 plasma concentrations.
Main Results:
- Elevated levels of C4d were found in 12/19 RA patients and 9/20 CD patients.
- Increased C3d levels were observed in 14/19 RA patients and 6/20 CD patients.
- Median C4d and C3d values were significantly elevated in both RA and CD groups, with a positive correlation between C3d and C4d (rs = 0.51-0.56, p < 0.005).
Conclusions:
- The data indicate activation of the classical complement pathway in both rheumatoid arthritis and Crohn's disease.
- Complement activation in RA and CD is characterized by increased levels of C3d and C4d, without a reduction in native C3 and C4.
- These findings suggest a potential role for the classical complement pathway in the pathogenesis of RA and CD.
Abstract:
Split products of complement component 3 (C3) and complement component 4 (C4) derived from activation of the alternative and classical complement pathways were measured in untreated outpatients, 20 with Crohn's disease and 19 with rheumatoid arthritis. Elevated levels of the d split product of C4 (C4d) were observed in 12 of 19 patients with rheumatoid arthritis and in 9 of 20 patients with Crohn's disease. Levels of the d split product of C3 (C3d) were increased in 14 of 19 patients with rheumatoid arthritis and in 6 of 20 Crohn's disease patients. The median values of C4d and C3d were significantly increased in both groups of patients. C3d concentrations correlated positively with C4d levels (rs = 0.51-0.56, p less than 0.005). The complement activation was not reflected in reduced plasma levels of native C3 and C4. The data indicate activation of the classical complement pathway in both rheumatoid arthritis and Crohn's disease.