Combined Immunoglobulin Free Light Chains Are Novel Predictors of Cardiovascular Events in Patients With Abdominal Aortic Aneurysm

Abstract

Abdominal aortic aneurysm (AAA) is characterised by the presence of B cells and immunoglobulins in the aortic wall, mainly in the adventitia. Kappa (κ) and lambda (λ) free light chains (FLCs) are produced from B cells during immunoglobulin synthesis. This study investigated the presence and prognostic value of combined FLCs (cFLCs or summed κ and λ) in patients with AAA. cFLCs were analysed by a turbidimetric specific assay in tissue conditioned media from AAA samples (n= 34) compared with healthy aortas (n= 34) from France and in plasma samples from patients with AAA (n= 434) and age matched controls (n= 104) selected from the Viborg Vascular (VIVA) AAA screening trial in Denmark. t test, logistic regression, and Cox regression were used to test whether plasma cFLCs serve as a marker for AAA presence and whether cFLCs were predictive of death, major adverse cardiovascular events (MACE), or major adverse lower limb events (MALE). Increased cFLC levels were detected in the AAA adventitial layer compared with the AAA medial layer and healthy media layer (13.65 ± 3.17 vs. 6.57 ± 1.01 vs. 0.49 ± 0.09 mg/L, respectively, p < .050). The upper tertile of plasma cFLCs was independently associated with AAA presence after correcting for confounders (odds ratio [OR] 7.596, 95% confidence intervals [CI] 3.117 - 18.513; p < .001). Of 434 patients with AAA, 89 (20.5%) died, 104 (24.0%) suffered MACE, and 63 (14.5%) suffered MALE, during a five year follow up. In univariable analysis, the cFLC upper tertile was associated with a higher risk of death, MACE, and MALE (p < .001 for all). After adjustment for confounders, cFLCs remained an independent predictor of all cause mortality (hazard ratio [HR] 4.310, 95% CI 2.157 - 8.609; p < .001), MACE (HR 2.153, 95% CI 1.218 - 3.804; p= .008), or MALE (HR 3.442, 95% CI 1.548 - 7.652; p= .002) for those in the upper tertile. Increased cFLCs are observed in adventitial tissue of patients with AAA, indicating local activation of B cells. Plasma cFLC levels are an independent predictor of death, MACE, and MALE in patients with AAA.