HMGB1+ microparticles present in urine are hallmarks of nephritis in patients with systemic lupus erythematosus

Abstract

Non-classical monocytes infiltrate the kidney parenchyma and participate in tissue damage in patients with lupus nephritis (LN). Circulating microparticles (MPs) seem to play critical roles in the activation of monocytes in systemic lupus erythematosus (SLE) patients. This study aims to characterize the phenotypes of MPs and monocyte subsets in LN patients and to determine their potential to discriminate between SLE patients with and without LN. Blood and urine samples from SLE patients were collected. In monocyte subsets from whole blood samples several phenotypic markers were evaluated. MPs were isolated from platelet-poor plasma and urine by centrifugation. This phenotypic marker characterization was performed using multiparametric flow cytometry. We observed that patients with active LN have lower counts of non-classical monocytes than do those without renal involvement. All monocyte subsets exhibited lower expression of CX3CR1 and ICAM-1 in LN than in patients without LN. High frequencies of MP-HMGB1⁺ and MP-HLA-DR⁺ were detected in circulation and urine of LN patients. Although MP-HMGB1⁺ , MP-HLA-DR⁺ , and MP-CX3CR1⁺ from urine were able to discriminate between patients with and without LN, only urinary MP-HMGB1⁺ were different between patients with active and inactive LN. Therefore, these vesicles may be useful as biomarkers of LN.

Keywords: CX3CR1; HMGB1; Microparticles; Monocyte subsets; Systemic lupus erythematosus.