Complement Factor C5a Is Increased in Blood of Patients with Abdominal Aortic Aneurysm and Has Prognostic Potential for Aneurysm Growth

Abstract

In this observational case-control study, circulating levels of complement factors C3a and C5a and leukotriene B4 (LTB4) were analysed in abdominal aortic aneurysm (AAA) patients regarding their association with diagnosis and prognosis. Serum C5a was significantly raised in AAA patients compared to healthy controls-median 84.5 ng/ml (IQR = 37.5 ng/ml) vs. 67.7 ng/ml (IQR = 26.2 ng/ml), p = 0.007-but was not elevated in patients with athero-occlusive disease. Serum C5a levels correlated significantly with the increase in maximum AAA diameter over the following 6 months (r = 0.319, p = 0.021). The median growth in the lowest quartile of C5a (< 70 ng/ml) was 50% less compared to the highest C5a quartile (> 101 ng/ml): 1.0 mm/6 months (IQR = 0.8 mm) vs. 2.0 mm/6 months (IQR = 1.5 mm), p = 0.014. A log-linear mixed model predicted AAA expansion based on current diameter and C5a level. To our knowledge, this is the first study linking complement activation, in particular C5a serum level, with AAA progression.

Keywords: Abdominal aortic aneurysm; C3a; C5a; Diagnosis; Leukotriene B4; Prognosis.

Fig. 1

Comparison of circulating C3a, C5a and LTB4 between AAA patients and controls. The complement factors C3a and C5a were measured in serum samples, while leukotriene B4 was assessed in plasma collected from AAA (N = 40) and healthy controls (N = 37). Boxplots illustrate the distribution of circulating levels of a C3a, b LTB4 and c C5a; p values refer to group comparisons by Mann-Whitney U test. d The diagnostic marker value of C5a was further evaluated by receiver operating characteristic (ROC) analysis and the area under the ROC curve (AUROC). e Serum C5a levels were further compared between healthy controls (N = 33) and patients with peripheral arterial disease (PAD, N = 24) or AAA (N = 33) by Mann-Whitney U test

Fig. 2

Association between baseline serum C5a and AAA growth in the following 6 months. For the exploration set of fifty-two 6-month monitoring periods, a the correlation of C5a serum values with subsequent AAA growth (in mm of maximal aortic diameter) over the next 6 months is illustrated by scatter plot and Spearman correlation coefficient. b AAA growth rates are depicted by boxplots according to C5a quartiles