Background/Purpose

Microparticles (MPs) are membrane-bound vesicles derived from vascular and intravascular cells such as endothelial cells (EMPs) and platelets (PMPs). MPs form during cell activation or apoptosis and may directly contribute to disease pathogenesis. Circulating MPs have been found to be higher in systemic sclerosis (SSc) compared with healthy controls, however their precise functional role remains to be elucidated. The present study was undertaken to establish whether plasma MP levels differ between primary Raynaud’s phenomenon (RP) and SSc and whether EMP and PMP levels correlate with dynamic assessment of digital microvascular function assessed using laser speckle contrast imaging (LSCI).

Methods

Patients with SSc (n=24, 22 with limited cutaneous SSc) and primary RP (n=16) not taking anti-platelet agents, NSAIDs or steroids were recruited to the study. Platelet-free plasma was obtained using citrated blood following a 2-step centrifugation regime. Digital perfusion at the volar aspect of the distal left middle finger was assessed using LSCI during a standardised local cold challenge (15°C for 60s). Digital perfusion was assessed at baseline, immediately following cold challenge (t0) and at 5 minute intervals during re-perfusion (t5, t10 and t15 respectively). Plasma levels of EMPs (AnnexinV+/CD31+/CD42b-) and PMPs (AnnexinV+/CD31+/CD42b+ or AnnexinV+/CD31-/CD42b+) were quantified using flow cytometry.

Results

Plasma levels of EMPs (161271/ml vs. 171318/ml) and PMPs (186348/ml vs. 246758/ml) did not differ between SSc and primary RP. Higher EMP levels were found in patients with SSc and a history of digital ulceration (DU) or digital pitting (DP) (median 198643/ml vs. 144840/ml, p=0.03). No additional associations between MP levels and disease characteristics were identified. Consistent positive correlations between MP levels and digital perfusion following cold challenge (but not at baseline) were identified in SSc (Table). In contrast, there were consistent negative correlations between PMP (but not EMP) levels and digital perfusion at both baseline and following cold challenge in primary RP (Table).

Conclusion

This is the first study to explore the relationship between circulating MP levels and peripheral microvascular dysfunction in primary RP and SSc. Higher EMPs were associated with a history of DU/DP in SSc. Higher EMP and PMP levels, however, were associated with higher digital perfusion following local cold challenge in SSc. In contrast, higher PMP levels were associated with lower digital perfusion in primary RP. There was no association between EMP levels and digital perfusion in primary RP. Additional work is needed to explore factors leading to MP generation and their contribution to peripheral microvascular dysfunction in primary RP and SSc. MPs may have the potential to act as biomarkers of peripheral microvascular dysfunction/damage in primary RP and SSc.

Table