The Relevance of Anti-PF4 Antibody Isotypes and Endogenous Glycosaminoglycans and their Relationship with Inflammatory Biomarkers in Pulmonary Embolism Patients

Abstract

Introduction Previous studies have shown that inflammation may contribute to the interplay of endogenous glycosaminoglycans (GAGs) and anti-PF4 antibodies. In this study, we quantified the levels of anti-PF4 antibody isotypes and endogenous GAGs together with inflammatory biomarkers in pulmonary embolism (PE) patients to determine whether there is a relationship in between. Identification of this relationship may provide insight to the complex pathophysiology of PE and HIT and may also be useful for development of potential prognostic, diagnostic and therapeutic interventions. Materials and Methods Plasma samples from PE patients (n: 210) were analyzed for anti-PF4 antibody isotypes and various thrombo-inflammatory cytokines utilizing commercially available biochip array and ELISA methods. The endogenous GAG levels in PE patients’ plasma were quantified using a fluorescence quenching method. The collected data analyzed to demonstrate the relationship between various parameters. Results The endogenous GAG levels were increased in the PE group ( P < .05). The levels of anti-PF4 antibody isotypes were higher in varying levels in comparison to the normal group ( P < .05). Inflammatory cytokines have shown varying levels of increase with IL-6, IL-8 and IL-10 showing the most pronounced values. Mortality outcome was related to increased GAGs and some of the cytokines. Conclusion In this study, we demonstrated increased levels of anti-PF4 antibody isotypes, endogenous GAGs, and inflammatory biomarkers in a large patient cohort in PE. The levels of the endogenous GAGs and inflammatory biomarkers were associated with PE severity and mortality. More studies are needed to understand this complex pathophysiology.

Endogenous Glycosaminoglycans in Various Pathologic Plasma Samples as Measured by a Fluorescent Quenching Method

“…75 In a recent analysis performed by our group, has shown that the levels of endogenous GAGs were elevated in PE patients, and this was also associated with PE severity and mortality. 76,77 In the current study, our findings are similar to a previous report showing elevated levels of endogenous GAGs in PE patient plasma compared to NHP, both before and after heparinase-I degradation which is likely the result of endothelial damage and glycocalyx degradation leading to PE development in these patients. The high percentage of decrease in endogenous GAG levels after heparinase-I administration might be the result of heparin contamination of plasma samples in which therapeutic heparin is the main treatment option in this patient group.…”

Glycemic Control and Plasma Levels of Pro-Inflammatory and Pro-Thrombotic Biomarkers in Diabetic Patients Presenting with Acute Pulmonary Embolism

“…Though their relevance has not yet been assessed in large scale studies it is likely that these may also serve as a key method of quantifying endothelial dysfunction. 30 Together with vWF, we considered these to be markers of endothelial dysfunction.…”