Liquid Biopsy Provides Insights into Lupus

Patients with systemic lupus erythematosus (SLE) produce autoantibodies to nuclear and membrane molecules. This immune response is, at least partially, driven by the non-histone nuclear protein known as HMGB1. HMGB1 is the prototypical alarmin in lupus, and it plays many diverse roles in the immune response.

Now, new research suggests that microparticles (MPs) in the serum of patients with SLE may be a source of extracellular HMGB1. The MPs can be characterized on the basis of their ability to bind to lactadherin: PS-positive (PS+) MPs bind to lactadherin, and PS-negative (PS−) MPs do not. Previous studies have shown that PS− MPs are more common in the blood of patients with SLE relative to controls. New results indicate that serum MP analysis may be able to serve as a liquid biopsy to determine if the patient is producing dead, dying and activated cells that are important for SLE pathogenesis.

Fariborz Mobarrez, PhD, a postdoctoral fellow at the Karolinska University Hospital in Sweden, and colleagues published the results of their analysis of MPs as they relate to SLE online on Oct. 25 in Scientific Reports.¹ The researchers evaluated 280 patients with a median disease duration of 13 years and searched for an association between levels of MPs in patients with SLE and clinical and serological variables.

“In assessing clinical association of MP levels in SLE, we found more robust clinical associations with PS− MPs than PS+ MPs,” explain the authors in their paper. “In accord with some previous studies, we did not find convincing associations with disease activity.”

The investigators confirmed that MPs occur in the blood of patients with SLE at levels that are 2–10 times greater than that seen in control patients. “Although we did not show a relationship of MP levels to disease activity, we did demonstrate that declining renal function is associated with fewer numbers of PS− MPs and PS+ PMPs,” explain the authors. They suggested in their paper that the abundance of the MPs, in general, and PS− MPs, in particular, in patients with SLE points to a generalized disturbance that is associated with pathology.

The detailed analysis of MPs revealed several notable differences in the numbers of various particle types seen in the blood of patients with SLE relative to matched controls. While platelet MPs (PMPs) were the most common particle type in both patients and controls, the investigators found approximately 10 times more C4d+ PMPs and five times more C4d+ endothelial-derived MPs (EMPs) in patients with SLE relative to controls. The levels of leukocyte-derived MPs (LMPs) were also approximately 2–7 times higher in the blood of patients with SLE than in controls.

“In our studies, PS− MPs in SLE were strongly associated with female gender, similar gender differences were not apparent in controls,” write the authors in their discussion. “This is an interesting observation, which should be further investigated as a possible clue to understand the striking female predominance in SLE. The high numbers of PS− MPs could result from masking of PS by other molecules, such as β2GP1 and annexin-V, which are abundant proteins in the circulation; both of these proteins can bind to PS.”

Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

Reference

1. Mobarrez F, Vikerfors A, Gustafsson JT, et al. Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations. Sci Rep. 2016 Oct 25;6:36025. doi: 10.1038/srep36025.