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. 2020 Oct;37(5):725-735.
doi: 10.5114/ada.2019.84230. Epub 2019 Apr 8.

Anti-endothelial cell antibodies are associated with apoptotic endothelial microparticles, endothelial sloughing and decrease in angiogenic progenitors in systemic sclerosis

Małgorzata M Michalska-Jakubus  1 , Marta Rusek  2 , Małgorzata Kowal  2 , Marcin Czop  3 , Janusz Kocki  3 , Dorota Krasowska  1
Affiliations

Anti-endothelial cell antibodies are associated with apoptotic endothelial microparticles, endothelial sloughing and decrease in angiogenic progenitors in systemic sclerosis

Małgorzata M Michalska-Jakubus et al. Postepy Dermatol Alergol. 2020 Oct.

Abstract

Introduction: Evidence has accumulated for the role of endothelial damage in systemic sclerosis (SSc) and the anti-endothelial cell antibodies (AECAs) might underlie vascular injury.

Aim: Since endothelial microparticles (EMPs) and circulating endothelial cells (CECs) reflect endothelial damage, we aimed to investigate their possible relationship with AECAs in SSc. We examined whether AECAs could affect endothelial repair based on the number of endothelial progenitor cells (EPCs).

Material and methods: Forty-seven SSc patients were screened. The AECAs were identified in serum by indirect immunofluorescence. EPCs and CECs were isolated from the peripheral blood using anti-CD34-based immunomagnetic separation, whereas EMPs were analyzed in plasma. Flow cytometry was used to quantify EMPs, CECs and EPCs.

Results: AECAs were found in 21 (44.7%) SSc patients and were significantly associated with higher levels of total as well as apoptotic (AnnV+ and CD51+) EMPs, whereas activated (CD62E+/AnnV-) EMPs did not differ between groups. Patients with AECAs had significantly elevated total CECs as well as activated CD105+ CECs. Total endothelial progenitors did not differ between patients with or without AECAs; however AECAs was negatively associated with the population of EPCs that express VEGFR2 or Tie2 receptors.

Conclusions: We found an association between AECAs and the severity of endothelial damage in SSc based on higher levels of total EMPs and CECs. In our study, AECAs were associated with apoptosis of ECs rather than their activation. We also identified a possible role of AECAs in the impairment of vascular repair in SSc as evidenced by significantly fewer angiogenic EPCs.

Keywords: anti-endothelial cell antibodies; endothelial cells; endothelial microparticles; systemic sclerosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Positive anti-endothelial cell reaction on human umbilical vein endothelial cells (HUVECs) and monkey skeletal muscles manifesting with cytoplasmic, granular, yellowish-green fluorescence concentrated around nuclei
Figure 2
Figure 2
Gating strategy for endothelial microparticles (EMPs) and representative dot plots of analyzed populations
Figure 3
Figure 3
Gating strategy for circulating endothelial cells (CECs)/endothelial progenitor cells (EPCs) and representative dot plots of different analyzed populations
Figure 4
Figure 4
Total, activated and apoptotic endothelial microparticles (EMPs) data for anti-endothelial cell antibody-positive and anti-endothelial cell antibody-negative systemic sclerosis patients presented as univariate scatterplots; Student’s t-test
Figure 5
Figure 5
Resting and activated circulating endothelial cells (CECs) data for anti-endothelial cell antibody-positive and anti-endothelial cell antibody-negative systemic sclerosis patients presented as univariate scatterplots; Student’s t-test
Figure 6
Figure 6
Data of different endothelial progenitor cells (EPCs) populations for anti-endothelial cell antibody-positive and anti-endothelial cell antibody-negative systemic sclerosis patients presented as univariate scatterplots; Student’s t-test
See this image and copyright information in PMC

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