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This is a Observational study (also classified as: Animal Study).

September 10, 2025Open Access

Anti-PS IgG Immune Complexes Impair Macrophage Phagocytosis in SLE via LOX-Dependent Oxidative Stress

Key Points

Anti-PS IgG immune-complexes significantly impair macrophage phagocytosis in systemic lupus erythematosus.
Patients with SLE and lupus nephritis showed elevated PS-IgG immune complex levels indicating their role as a strong biomarker.
The study used a combination of in vitro and in vivo approaches to assess oxidative stress and phagocytic function.
Findings suggest that targeting oxidative stress may restore macrophage functions in SLE and lupus nephritis.

Abstract

Systemic lupus erythematosus (SLE) is a severe autoimmune disease with systemic complications mediated by immune-complex formation. The elevated level of anti-phosphatidylserine (PS) IgG has been implicated in SLE pathogenesis. In this study, we aimed to explore the effector mechanisms of PS immune-complex during lupus development. Serological profiles of immune-complexes in SLE patients were analyzed. Immunofluorescence staining showed PS-IgG immune-complex deposition in kidney biopsies of lupus nephritis patients. C57BL/6J mice were immunized with PS for immune-complex and renal function assessment. The roles of PS-IgG immune-complex and lysyl oxidase (LOX) were validated from SLE PBMCs, THP-1 cell line and PS-immunized lupus mice. The intracellular reactive oxygen species (ROS) levels, and phagocytosis function were examined by flow cytometry in SLE PBMCs, THP-1 cell line and PS-immunized lupus mice. For in vitro treatment, the effects of antioxidant N-acetylcysteine (NAC) and LOX inhibitor β-Aminopropionitrile (BAPN) were verified in THP-1 cell line and cells from PS-immunized lupus mice. SLE and lupus nephritis (LN) patients showed significant elevated circulating and glomerular PS-IgG immune-complex levels. ROC analysis indicated PS-IgG immune-complex as a strong biomarker in SLE and LN. Mechanistically, induced macrophages from SLE patients treated with PS-IgG immune-complex significantly increased cytoplasmic ROS levels, elevated LOX expression and exhibited dampened phagocytotic function. In mice, PS immunization triggered PS-IgG immune complex formation, increased LOX expression, immune-complex deposited glomerular nephritis, and impaired phagocytotic function of macrophages. NAC and BAPN treatment restored the phagocytotic function of human and murine macrophages. Our results indicate that PS-IgG immune-complex can directly impair macrophage phagocytotic functions via LOX mediated-oxidative stress and may serve as a novel biomarker for SLE.

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