Abstract Number: PB2202
Meeting: ISTH 2020 Congress
Theme: Venous Thromboembolism and Cardioembolism » Post-thrombotic Syndrome
Background: Following deep vein thrombosis (DVT), one in three patients experiences chronic signs and symptoms in the affected leg, referred to as post-thrombotic syndrome (PTS). Inadequate thrombus resolution, resulting in vein damage and venous hypertension, is is considered a key player in the onset of PTS. Since thrombus resolution is guided by leukocytes, a better understanding of their role could benefit preventive treatment. This is the first transcriptomics study to address this subject.
Aims: To identify differences in leukocyte gene expression between patients with and without PTS.
Methods: We performed a case-control study on a prospectively followed cohort consisting of 30 patients with PTS (cases), 30 patients with a history of DVT without PTS (controls) and 30 healthy individuals (HI) matched for age, gender and BMI. The medical ethical committee of the MUMC+ approved this study and all participants gave written informed consent. Based on the integrity of RNA isolated from buffy coats, a subpopulation of 20 participants was selected for subsequent directional mRNA sequencing (~30M reads/sample). Reads were aligned to the human transcriptome and analyzed with DESeq2. Differentially expressed genes (DEGs) with a false discovery rate adjusted
p-value< 0.1 were considered significant. Pathogenically relevant DEGs were selected for confirmation by quantitative polymerase chain reaction (qPCR).
Results: Our subpopulation of 6 cases, 7 controls and 7 HI had no significant differences in baseline characteristics. We found thirteen DEGs originating solely from the comparison of cases with controls (Table 1). Four DEGs were identified as pathogenically relevant (Figure 1): an angiogenic growth factor (HDGFL3), an antigen-recognizing molecule (HLA-DPA1), a thrombo-inflammatory modulator (PPIA) and an inflammation regulating receptor (ADIPOR1). qPCR could not confirm mRNA-sequencing findings in these four DEGs, a common problem in transcriptomic studies.
Conclusions: Our study uncovered differences in leukocyte gene expression which might provide novel biomarkers or therapeutic targets if validated by future research.
| Gene name | Log2 fold change | Adjusted p-value | Gene name | Log2 fold change | Adjusted p-value |
| HDGFL3 | 0.61 | 0.02 | RPS14 | -0.65 | 0.09 |
| RPL13A | -0.64 | 0.09 | PPIA | -1.33 | 0.09 |
| RPL12 | -0.75 | 0.09 | KCNQ1OT1 | 0.92 | 0.09 |
| AC011462.2 | 0.80 | 0.09 | ADIPOR1 | -1.81 | 0.09 |
| AC092384.2 | 0.93 | 0.09 | AL596202.1 | 1.57 | 0.09 |
| AF127577.1 | -0.71 | 0.09 | RPL41 | -0.98 | 0.09 |
| HLA-DPA1 | 9.51 | 0.09 |
[Identified DEGs (adjusted p-value < 0.1) in a comparison of cases vs. controls]
[Overview of functional pathways for Adipo(nectin) receptor ADIPOR1, HDGFL3, PPIA encoding Cyclophilin (CyPA) and antigen (Ag) recognizing HLA-DPA1.]
To cite this abstract in AMA style:
Iding AFJ, Witten A, Isaacs A, Castoldi E, ten Cate H, Stoll M, ten Cate-Hoek AJ. Leukocyte Gene Expression in Post-Thrombotic Syndrome [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/leukocyte-gene-expression-in-post-thrombotic-syndrome/. Accessed November 30, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/leukocyte-gene-expression-in-post-thrombotic-syndrome/