The Diagnostic Utility of Natural Killer Cell Subsets in Deep Vein Thrombosis

Abstract

Background

Natural killer (NK) cells are important components of adaptive and innate immune responses. NK cell subsets have different functions and may play a role in vascular disorders. This study aimed to evaluate the proportions of NK cells and their subsets to determine whether they can be used as markers of venous thrombosis and to identify whether there was a link between NK cell proportion and citrullinated histone (H3) levels.

Patients and Methods

This study included 100 participants divided into Group I (n=50, patients with deep venous thrombosis (DVT)) and Group II (n=50, age- and sex-matched healthy controls). Group I was further categorized into Group Ia (n=25, patients with acute DVT) and Group Ib (n=25, patients with chronic DVT). The proportions of NK cells and their subsets were evaluated by flow cytometry using CD3/CD16/CD56. The levels of citrullinated histones (H3) were estimated using enzyme-linked immunosorbent assay (ELISA).

Results

Compared to the control group, DVT patients had a significantly lower proportion of (CD56 dim/CD16+) NK cells, a significantly higher proportion of (CD56-/CD16+) NK cells and a high level of citrullinated histone (H3).

Conclusion

NK cell subsets and citrullinated histone (H3) could be used as markers for DVT and as targets for therapeutic drugs to inhibit the formation or progression of thrombosis.

Keywords:

• natural killer cell
• natural killer cell subsets
• citrullinated histone
• deep venous thrombosis

Abbreviations

VTE, Venous thromboembolism; NETs, neutrophil extracellular traps; IFN-γ, interferon-γ; NK cells, natural killer cells; DVT, deep vein thrombosis; IRB, Institutional Review Board; ELISA, enzyme-linked immunosorbent assay; FSC/SSC, forward scatter/ side scatter; PT, prothrombin time; INR, international normalization ratio; APTT, activated partial thromboplastin time; ROC curve, receiver operating characteristic curve; AUC, area under the curve.

Acknowledgments

We would like to thank all participants in this study. Many thanks to Dr Walied Khereba for his help in the revision of the manuscript.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.