Activation of the classical complement pathway in spontaneous bacterial peritonitis

Area of Science:

• Immunology
• Gastroenterology
• Clinical Medicine

Background:

• Severe liver disease often presents with low plasma and ascitic fluid complement concentrations.
• Spontaneous bacterial peritonitis (SBP) is a common complication in patients with severe liver disease.
• The cause of low complement levels in these patients, whether consumption or impaired synthesis, requires investigation.

Purpose of the Study:

• To investigate if low complement concentrations in severe liver disease patients are due to complement consumption.
• To determine the role of complement activation pathways in patients with and without SBP.

Main Methods:

• Studied complement activation in 32 patients with severe liver disease, including 11 with SBP.
• Measured plasma and ascitic fluid concentrations of C3, C4, factor B, and activation markers (C3d/C3, C4d/C4, Ba/B).
• Compared complement levels and activation markers between SBP and non-SBP patient groups.

Main Results:

• Patients with SBP had significantly lower plasma C3 and C4 compared to uninfected patients.
• Increased classical pathway activation (C4d/C4, C3d/C3) was observed in SBP patients' plasma.
• Ascitic C3 consumption (C3d/C3) was higher in SBP patients, correlating with lower ascitic C3 concentrations.

Conclusions:

• Decreased plasma C3 and C4 in SBP are primarily caused by increased classical pathway activation, not impaired hepatic synthesis.
• Complement C3 consumption contributes to low ascitic C3 levels observed in SBP.
• Findings highlight the role of complement activation and consumption in the pathophysiology of SBP in severe liver disease.