Active systemic lupus erythematosus is associated with failure of antigen-presenting cells to express programmed death ligand-1
RHEUMATOLOGY
Authors: Mozaffarian, N.; Wiedeman, A. E.; Stevens, A. M.
Abstract
Objective. Antigen-presenting cells (APC) play critical roles in establishing and maintaining peripheral tolerance. This is accomplished in part via expression of negative co-stimulatory molecules such as programmed death ligand-1 (PD-L1) on tolerogenic APC, such as immature myeloid dendritic cells (mDC). Several studies have strongly linked dysfunction of APC, including mDC, to the pathogenesis of SLE. The objective of this study was to determine whether APC expressed PD-L1 protein at normal levels during active lupus. Methods. Peripheral blood mononuclear cells (PBMC) were isolated from 19 paediatric patients with SLE and from 17 healthy age-matched controls. PBMC from both cohorts were cultured in the absence of exogenously added stimuli, and leucocyte PD-L1 expression was measured by flow cytometry. Results. Immature mDC and monocytes (Mo) from healthy children expressed little PD-L1 at initial isolation, but spontaneously up-regulated PD-L1 by 24 h. In contrast, both mDC and Mo from patients with active SLE failed to up-regulate PD-L1 over a 5 day time course, expressing this protein only during disease remissions. Conclusions. These data are the first to link active lupus with reversibly decreased PD-L1 expression on professional APC, suggesting a novel mechanism for loss of peripheral tolerance in SLE.
Programmed Death-1: From gene to protein in autoimmune human myasthenia gravis
JOURNAL OF NEUROIMMUNOLOGY
Authors: Sakthivel, Priya; RamanujaM, Ryan; Wang, Xiong Biao; Pirskanen, Ritva; Lefvert, Ann Kari
Abstract
The key role of an inhibitory receptor, Programmed Death-1, has been evaluated in 273 patients with autoimmune myasthenia gravis. At the genetic level, SNP's genotyping showed no significant association to the disease. Gene expressions in patients were not different from that in controls. Interestingly, at the cell-surface protein level, there were significant elevated levels of PD-1 on T cells and its ligand PD-L1 on monocytes in the patients compared to controls. However, we could not demonstrate any secreted soluble forms of PDA among the patients and controls. Thus, our study shows PD-1 might have a natural regulatory property behind MG. (C) 2007 Elsevier B.V. All rights reserved.
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