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Published on: August 26, 2017
Mammalian Target of Rapamycin Pathway Assessment in Antiphospholipid Antibody-Positive Patients with Livedo
Ecem Sevim1, Salma Siddique2, Madhavi Latha S Chalasani3
1E. Sevim, MD, Department of Rheumatology, Hospital for Special Surgery, New York, and Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA; ecemsevim@gmail.com.
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: (1) persistently aPL-positive with systemic lupus erythematosus (SLE); (2) persistently aPL-positive without SLE; and (3) aPL-negative SLE (control). After collecting aPL-related medical history, two 5-mm skin biopsies of livedo were performed on each patient: (1) peripheral (erythematous-violaceous lesion); and (2) central (nonviolaceous area). We stained specimens for phosphorylated protein kinase B (p-AKT) and phosphorylated 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 test and Wilcoxon signed-rank test.
Results:
Ten patients with livedo reticularis were enrolled: 4 aPL-positive without SLE (antiphospholipid syndrome [APS] classification met, n = 3), 4 aPL-positive SLE (APS classification met, n = 3), and 2 aPL-negative SLE (control). 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 patients with SLE, with more prominent activity in the lower basal layers of the epidermis. These findings may serve as a basis for further investigating the mTOR pathway in aPL-positive patients.
Insights
Antiphospholipid antibody (aPL) nephropathy involves increased mammalian target of rapamycin (mTOR) pathway activation in the skin of affected patients. This mTOR activation was observed in livedoid lesions of aPL-positive individuals, with or without systemic lupus erythematosus (SLE).
Area of Science:
- Immunodermatology
- Rheumatology
- Molecular Biology
Background:
- Antiphospholipid antibody (aPL) nephropathy is linked to mammalian target of rapamycin (mTOR) pathway activation, contributing to microvascular disease.
- Endothelial cell proliferation is a hallmark of aPL-related microvascular disease.
- Investigating mTOR activation in skin lesions may provide insights into aPL pathophysiology.
Purpose of the Study:
- To examine mammalian target of rapamycin (mTOR) pathway activation in the skin of patients with antiphospholipid antibodies (aPL) and livedo.
- To compare mTOR activity in livedoid lesions between aPL-positive patients (with and without SLE) and aPL-negative SLE controls.
Main Methods:
- Study included three groups: aPL-positive SLE, aPL-positive without SLE, and aPL-negative SLE (control).
- Skin biopsies from peripheral (lesional) and central (non-lesional) areas were analyzed.
- Immunohistochemistry was used to detect phosphorylated protein kinase B (p-AKT) and phosphorylated S6 ribosomal protein (p-S6RP) as markers of mTOR activity, alongside endothelial cell (CD31) and proliferation (Ki-67) markers.
Main Results:
- Ten patients with livedo reticularis were enrolled.
- Epidermal p-AKT and p-S6RP staining, indicating mTOR activity, were significantly increased in aPL-positive patients (with or without SLE) compared to aPL-negative SLE controls.
- Increased mTOR activity was more pronounced in the lower basal layers of the epidermis and observed in both peripheral and central skin samples.
Conclusions:
- This study demonstrates elevated mTOR pathway activity in the livedoid lesions of aPL-positive patients, irrespective of SLE status.
- The findings highlight the role of mTOR activation in the skin manifestations of aPL-related conditions.
- Further research into the mTOR pathway in aPL-positive patients is warranted.
