Complement in asthma: sensitivity to activation and generation of C3a and C5a via the different complement pathways

Area of Science:

• Immunology
• Pulmonology
• Genetics

Background:

• Rodent studies suggest complement's role in airway hyperresponsiveness (AHR) and asthma.
• Asthma susceptibility may stem from abnormal complement activation or cellular response to its products.
• Previous research indicates normal total complement levels in asthmatics, but potential abnormal activation sensitivity.

Purpose of the Study:

• To investigate if complement in atopic asthma patients exhibits increased activation propensity compared to nonatopic controls.
• To explore potential gain or loss of function in complement proteins without altering total levels.

Main Methods:

• In vitro induction of complement activation via classical, alternative, and lectin pathways in plasma from asthmatics and controls.
• Measurement of complement activation products, including C3a, C3 fragments, and C5a.
• Analysis of basal C3a and C5a levels and mannan-binding lectin (MBL) levels.

Main Results:

• No significant differences in generated C3a, C3 fragments, or C5a were observed between asthmatics and controls for any pathway.
• C3a/C3 and C5a/C5 ratios were similar in both groups, indicating comparable complement activation efficiency.
• Basal plasma levels of C3a and C5a were alike; however, mannan-binding lectin (MBL) levels were moderately elevated in asthmatics.

Conclusions:

• Complement activation does not appear to be abnormally sensitive in asthmatic patients across the classical, alternative, or lectin pathways.
• Elevated MBL levels in asthmatics warrant further investigation regarding their specific role in asthma pathogenesis.
• The study suggests that intrinsic abnormalities in complement activation sensitivity are unlikely to be a primary driver of asthma susceptibility.