ZURICH, Switzerland—Microparticles—small, membrane, coated vesicles—may contribute to disease pathogenesis in systemic scleroderma (SSc), according to new research in the September issue of Arthritis & Rheumatism.¹

“This study is the first to show that the levels of microparticles are elevated in the blood of patients with SSc, suggesting that this novel mechanism of intercellular interaction can contribute to disease pathogenesis,” conclude the researchers led by Serena Guiducci, MD, of University Hospital Zurich in Switzerland.

Not just innocent bystanders

Microparticles derived from platelets, endothelial cells, monocytes, and T-cells were significantly more common in the SSC patient, which reflects the activation of these cells. Microparticles are released during both cell activation and cell death and may be important mediators of cellular communication.

The new study examined blood samples from seven SSc patients and 15 sex- and age-matched non-SSc controls. The investigators reported that the total number of microparticles was greatly increased in patients with SSc compared with healthy controls (mean ± SEM 88 ± 4.8 x 105 microparticles/mL plasma vs 42.3 ± 9.4 x 105 microparticles/mL plasma; P <.001). Platelets were the most common source of microparticles in both SSc patients and healthy controls. Endothelial cells were the second most common source in both groups.

Skin disease worsens as microparticles increase

The modified Rodnan skin thickness score (MRSS) was inversely correlated with the total number of microparticles. Patients with cutaneous ulcers showed a significantly lower total number of microparticles.

A multivariate analysis showed that an additive model of age, C-reactive protein, MRSS, and subtype of disease accounted for 55% of the variability of the total microparticle count (r = 0.744), suggesting that microparticles may at least be biomarkers of disease activity in SSc, if not contributors to disease activity.

David S. Pisetsky, MD, PhD, chief of the division of rheumatology at Duke University Medical Center in Durham, North Carolina, is one of the study coauthors. He told MSKreport.com that microparticles might be useful biomarkers in SSc. “One of the issues in scleroderma is how do we assess activity and what is the course of the disease. The literature is emerging on the biomarker potential of microparticles in other disease like atherosclerosis and diabetes, and they may also be useful markers in scleroderma. There is a growing literature that microparticles have a direct and fairly profound activity on the vessels themselves and have immunological effects. They are not inert, and they are not debris.”

Translating research into practice

If microparticles do play a role in the pathogenesis of SSc, the question becomes whether they can be targeted to minimize disease activity.

“Theoretically,” Dr. Pisetsky said, “therapy could decrease their production. This might involve a variety of nonspecific methods. The other [potential treatment] method is to understand the signal transduction pathways that microparticles activate. We don’t know the full story yet, but are there any unique pathways that we could target?”

Particle clearance might also be helpful. “In lupus, there is a lot of interest in agents that affect clearance,” Dr. Pisetsky said. “We are trying all these approaches.”

Reference

1. Guiducci S, Distler JHW, Jüngel A, et al. The relationship between plasma microparticles and disease manifestations in patients with systemic sclerosis. Arthritis Rheum. 2008;58:2845-2853.