Neutrophil Heterogeneity Identifies an Association of LAMP1 With Proliferative Lupus Nephritis

TL;DR

Researchers found that LAMP1, a protein on activated neutrophils, is elevated in lupus patients and could serve as a noninvasive biomarker for severe kidney disease in lupus.

Contribution

The study identifies LAMP1 as a novel marker of neutrophil activation and potential biomarker for proliferative lupus nephritis.

Findings

LAMP1 is expressed on the surface of activated neutrophils in lupus patients but not in healthy controls.

Serum and urinary LAMP1 levels are significantly higher in lupus patients, especially those with proliferative lupus nephritis.

Urinary LAMP1 correlates with disease severity markers like proteinuria and glomerular filtration rate.

Abstract

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) with limited biomarkers for early detection. While neutrophils contribute to SLE pathogenesis, their phenotypic heterogeneity in disease remains poorly characterized. Here, we used mass cytometry to profile blood neutrophils from patients with biopsy‐confirmed proliferative LN and healthy controls. We identified a distinct population of activated neutrophils, marked by surface expression of lysosomal‐associated membrane protein 1 (LAMP1/CD107a), that was virtually absent in healthy individuals. We demonstrate that LAMP1 resides intracellularly in resting neutrophils and translocates to the cell surface upon activation. Transcriptomic analysis revealed no difference in LAMP1 mRNA expression between patients with SLE and controls, confirming that surface LAMP1 reflects neutrophil activation rather than increased transcription. Soluble LAMP1 was significantly elevated in serum from patients with SLE compared with controls, with the highest levels in proliferative LN. In a large cohort of 225 patients with LN, urinary LAMP1 correlated with glomerular filtration rate, proteinuria, and histological activity indices. Together, our findings reveal LAMP1 as a marker of neutrophil activation in SLE and identify serum and urinary LAMP1 as potential noninvasive biomarkers for proliferative LN.

We investigated neutrophil heterogeneity in patients with systemic lupus erythematosus and identified increased surface levels of LAMP1 (CD107a). Stimulation of healthy donor neutrophils led to increased surface LAMP1. Urine and serum soluble LAMP1 levels were increased in patients, especially those with proliferative lupus nephritis.

Figures