Title: Exploring Immune-Mediated Brain Function Abnormalities in Systemic Lupus Erythematosus: Neuroimaging Evidence of the Impact of Anti-Ribosomal P Protein Antibodies

Abstract

Objectives: Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most severe complications of systemic lupus erythematosus (SLE), and its early biomarkers and immune mechanisms remain unclear. This study utilizes Resting-State functional magnetic resonance imaging (rs-fMRI) to explore early neuroimaging biomarkers and potential immune mechanisms of brain injury in SLE, with a particular focus on anti-ribosomal P protein antibody (ARPA).

Methods: A total of 47 SLE patients and 33 healthy controls (HCs) underwent rs-fMRI. Amplitude of low-frequency fluctuations (ALFF) and degree centrality (DC) values were compared between SLE and HC groups, and between ARPA-positive and ARPA-negative SLE patients. Correlation analyses were conducted to evaluate relationships between neuroimaging indicators and clinical indicators, including immunoglobulins and antiphospholipid antibodies. Conventional MRI findings, including white matter hyperintensities (WMHs), were also assessed.

Results: SLE patients exhibited significant ALFF and DC alterations in regions associated with cognitive and sensory functions, including the inferior frontal and occipital regions. Notably, ARPA-positive SLE patients showed increased ALFF and DC values in areas related to cognitive and emotional regulation. Additionally, ACA-IgM and IgG correlate with brain injury in ARPA-positive patients. WMHs were more prevalent in ARPA-positive patients, with age and IgG levels identified as predictive markers for WMHs.

Conclusions: The combined use of ALFF and DC can effectively identify early biomarkers of brain injury in SLE patients. ARPA may synergize with other immune factors to combine to impair some brain functions, offering new insights into the immune-mediated mechanisms of SLE-related brain injury and potential targets for therapeutic interventions.