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Complement activation and plasma levels of C4b-binding protein in critical limb ischemia patients

Myriam Martin1, Anders Gottsäter, Peter M Nilsson

  • 1University of Lund, Department of Laboratory Medicine, Malmö University Hospital, Malmö, Sweden.

Journal of Vascular Surgery
|July 1, 2009
PubMed

Insights

Elevated complement activation and C4b-binding protein (C4BP) levels indicate critical limb ischemia (CLI) severity. These markers, along with others, aid in understanding CLI pathophysiology.

Area of Science:

  • Biochemistry
  • Immunology
  • Vascular Medicine

Background:

  • Critical limb ischemia (CLI) is a severe peripheral arterial disease characterized by significantly reduced blood flow to the legs, leading to pain, nonhealing wounds, and gangrene.
  • Tissue necrosis in CLI activates the complement system, leading to the binding of complement inhibitor C4b-binding protein (C4BP).
  • Two C4BP isoforms exist: C4BP(beta) and an inflammation-associated isoform composed solely of alpha-chains; total C4BP (C4BP(tot)) measures both.

Purpose of the Study:

  • To investigate whether complement activation and C4BP levels predict the severity of critical limb ischemia (CLI).
  • To assess the clinical utility of measuring complement activation and C4BP in CLI patients.

Main Methods:

  • A prospective study of 259 CLI patients and 219 healthy controls.
  • Measured plasma levels of soluble terminal complement complexes (C5b-9), C4BP(tot), C4BP(beta), inflammatory mediators (e.g., IL-6, hs-CRP), lipids, homocysteine, and endothelin-1.
  • Assessed resistance to activated protein C and ankle blood pressure.

Main Results:

  • CLI patients exhibited significantly higher systemic complement activation compared to controls (P < .0001).
  • Patients with gangrene showed even higher complement activation and increased C4BP levels (C4BP(tot) P = .0248; C4BP(beta) P = .0581).
  • Elevated C4BP plasma levels in CLI patients correlated with IL-6, hs-CRP, leukocyte and platelet counts, and HDL levels.

Conclusions:

  • Increased complement activation and C4BP plasma levels are associated with greater tissue necrosis and disease severity in critical limb ischemia.
  • These findings, combined with correlations to other biomarkers, enhance understanding of CLI pathophysiology.
  • Measurement of complement activation and C4BP may offer clinical advantages in assessing CLI severity.
Abstract

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