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. 2022 Jan-Dec:28:10760296221091770.
doi: 10.1177/10760296221091770.

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

Bulent Kantarcioglu  1 , Amir Darki  2   3 , Fakiha Siddiqui  1 , Debra Hoppensteadt  1 , Joseph Lewis  1 , Roland Krämer  4 , Cafer Adiguzel  5 , Jawed Fareed  1
Affiliations

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

Bulent Kantarcioglu et al. Clin Appl Thromb Hemost. 2022 Jan-Dec.

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.

Keywords: COVID-19; anti-PF4 antibodies; glycosaminoglycans; inflammatory biomarkers; pulmonary embolism.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
The Levels of Anti-PF4 Antibody Isotypes and Endogenous GAGs in acute PE patients and healthy controls. The levels of anti-PF4 Ig A, Ig G and endogenous GAGs were significantly elevated in acute PE patients compared to normal healthy individuals (Panel A, B and D). The increase in anti-PF4 Ig M was not statistically significant (Panel C).
Figure 2.
Figure 2.
The Levels of Anti-PF4 Antibody Isotypes and Endogenous GAGs According to PE Severity. There was no significant difference in the levels of anti-PF4 antibody isotypes according to severity of acute PE (Panel A, B and C). The levels of endogenous GAGs were significantly higher in massive acute PE patients (Panel D).
Figure 3.
Figure 3.
The Levels of Anti-PF4 Antibody Isotypes and Endogenous GAGs According to 30-day Mortality. There was no significant difference in the levels of anti-PF4 antibody isotypes according to 30-day mortality of acute PE patients (Panel A, B and D). The levels of endogenous GAGs were significantly higher among patients deceased within 30 day of PE diagnosis (Panel D).
Figure 4.
Figure 4.
Heatmap that shows the correlations between the levels of anti-PF4 isotypes and endogenous GAGs.
Figure 5.
Figure 5.
Pulmonary embolism results in the generation of thrombin and tissue factor which are capable of activating platelets and cells. Damaged endothelium results in the generation of GAGs which complex with the PF4 released from platelets. This complex results in the generation of anti-heparin-PF4 antibodies which in turn further amplify activation of cells and platelets resulting in the formation of inflammatory mediators.
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