Mammalian Target of Rapamycin Pathway Assessment in Antiphospholipid Antibody Positive Patients with Livedo.

Overview

abstract

OBJECTIVE: In antiphospholipid antibody (aPL) nephropathy, activation of the mammalian target of rapamycin (mTOR) contributes to endothelial cell proliferation, a key finding of aPL microvascular disease. Here, we examined mTOR activation in the skin of aPL-positive patients with livedo. METHODS: Three patient groups with livedo were studied: persistently aPL-positive with or without systemic lupus erythematosus (SLE), and aPL-negative SLE (control). After collecting aPL-related medical history, two 5-mm skin biopsies of livedo were performed on each patient: a) peripheral (erythematous-violaceous lesion), b) central (non-violaceous area). We stained specimens for phosphorylated protein kinase B (P-AKT) and S6 ribosomal protein (P-S6RP) as mTOR activity markers, CD31 to identify endothelial cells, and Ki-67 to show cellular proliferation. We counted cells in the epidermis and compared mTOR positive cell counts between peripheral and central samples, and between patient groups, using Freidman and Wilcoxon Rank tests. RESULTS: Ten patients with livedo reticularis were enrolled (aPL-positive without SLE: 4 [APS classification met: 3], aPL-positive SLE: 4 [APS classification met: 3], and aPL-negative SLE [control]: 2). In all aPL-positive patients, epidermal P-AKT and P-S6RP staining were significantly increased in both peripheral and central skin samples when compared to aPL-negative SLE controls; both were more pronounced in the lower basal layers of epidermis. CONCLUSION: Our study demonstrates increased mTOR activity in livedoid lesions of aPL-positive patients with or without SLE, compared to aPL-negative SLE patients, more profoundly in the lower basal layers of epidermis. These findings may serve as a basis for further investigating mTOR pathway in aPL-positive patients.