RT Journal Article
SR Electronic
T1 Mammalian Target of Rapamycin Pathway Assessment in Antiphospholipid Antibody–Positive Patients with Livedo
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1026
OP 1030
DO 10.3899/jrheum.220049
VO 49
IS 9
A1 Ecem Sevim
A1 Salma Siddique
A1 Madhavi Latha S. Chalasani
A1 Susan Chyou
A1 William D. Shipman
A1 Orla O’Shea
A1 Joanna Harp
A1 Oral Alpan
A1 Stéphane Zuily
A1 Theresa T. Lu
A1 Doruk Erkan
YR 2022
UL http://www.jrheum.org/content/49/9/1026.abstract
AB 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.