Elevated serum MFG‐E8 level is possibly associated with the presence of high‐intensity cerebral lesions on magnetic resonance imaging in patients with systemic lupus erythematosus

Abstract

Human milk fat globule-EGF factor 8 (MFG-E8), also known as lactadherin, is a secreted glycoprotein that plays essential roles in the clearance of apoptotic cells and angiogenesis. It has been reported that serum MFG-E8 levels are higher in systemic lupus erythematosus (SLE) patients compared with in healthy controls; however, a previous study reported no correlation between serum MFG-E8 levels and SLE disease activity. The objective of this study was to assess serum MFG-E8 levels and their clinical associations in patients with SLE. Serum MFG-E8 levels in 49 Japanese patients with SLE, eight with cutaneous LE, and 28 healthy controls were examined. Serum MFG-E8 levels in SLE patients were significantly higher than those in cutaneous LE patients and healthy individuals. In addition, serum MFG-E8 levels were positively correlated with the SLE Disease Activity Index score, which reflects the disease activity of SLE. Notably, the frequency of the presence of high-intensity cerebral lesions on MRI in the SLE patients with elevated serum MFG-E8 levels was significantly higher than that in SLE patients with normal serum MFG-E8 levels. These findings suggest that elevated serum MFG-E8 levels may be associated with cerebrovascular diseases or neuropsychiatric SLE in patients with SLE, and that the measurement of serum MFG-E8 levels in SLE patients is useful for risk stratification of cerebrovascular disease or cerebrovascular diseaserelated neuropsychiatric SLE.

Polymorphisms of MFGE8 are associated with susceptibility and clinical manifestations through gene expression modulation in Koreans with systemic lupus erythematosus

“…Therefore, the expression level of MFGE8 is a very important factor in its function, and can be said to be related to the pathogenesis of autoimmune diseases including SLE. In addition, serum MFGE8 levels in Japanese patients with SLE were significantly higher than those in healthy individuals 23,28 . Moreover, the medical treatment of SLE resulted in significantly lower levels of MFGE8.…”

Suppressive Regulation by MFG‐E8 of Latent Transforming Growth Factor β–Induced Fibrosis via Binding to αv Integrin: Significance in the Pathogenesis of Fibrosis in Systemic Sclerosis

“…It has been reported that MFG‐E8 is implicated in the pathogenesis of autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The serum MFG‐E8 level in SLE patients was higher than that in healthy individuals , and aged MFG‐E8–knockout (KO) mice developed glomerulonephritis and showed antinuclear antibody (ANA) production . Serum MFG‐E8 levels in RA patients and arthritic mice were significantly lower than those in healthy controls, and MFG‐E8–KO mice exhibited exacerbated arthritis .…”

An integrin/MFG-E8 shuttle loads HIV-1 viral-like particles onto follicular dendritic cells in mouse lymph node

“…While PS is normally located on the plasma membrane inner leaflet during viral budding the PS becomes exposed on the HIV-1 envelope potentially serving as a target for MFG-E8 and related PS binding proteins (Morizono and Chen, 2014; Wu and Shroff, 2018). Because MFG-E8 is widely expressed and found at substantial concentrations in blood and potentially the lymph (Kishi et al, 2017; Yamaguchi et al, 2008); most HIV-1 virions likely bear MFG-E8. This would target HIV-1 virions to monocytes and macrophages that express αvβ3/5 integrins.…”