Takayasu's arteritis (TA) is a rare primary and granulomatous large vessel vasculitis of unknown origin that predominantly affects the aorta and itsmajor branches. It has been shown toaffect individuals of anyage, gender and a wide variety of ethnic and racial population worldwide. The pathophysiology of TA is complex and multi-factorial and the exact pathogenesis remains to be elucidated; however, participation of autoimmunity, inflammation and oxidative stress has potentially been implicated [1–3]. Receptor for advanced glycation endproducts (RAGE) is amemberof the immunoglobulin superfamily and is expressed on the surface of various cells e.g. endothelium, mononuclear phagocytes, lymphocytes and smooth muscle cells. Extracellular newly identified RAGE-binding protein (EN-RAGE or S100A12), an inflammatory ligand of RAGE, is a member of the S100 protein family. Since its discovery twodecades back [4], the inflammatory role of RAGE and EN-RAGE interaction is nowwell established in various chronic inflammatory disorders. RAGE has a circulating truncated variant isoform and soluble RAGE (sRAGE), corresponds to its extracellular domain only. By competing with cell-surface RAGE for ligand binding, sRAGE contributes to the removal/neutralization of circulating ligands, thus, functioning as a decoy [5–7]. Previously, we demonstrated low sRAGE levels showing inverse correlation with MMPs in a group of forty TA subjects as compared to controls [8]. Keeping in mind the importance of RAGE biology in various diseases, we thought it worth to determine the expression of RAGE and its inflammatory ligand EN-RAGE at transcriptional level in peripheral blood mononuclear cells (PBMCs) fromTA subjects. For this, 24 subjectswith TA and 24 normal healthy controls were recruited as described previously [3,8,9]. The Institutional Ethics Committee approved the present study. Venous blood was collected from overnight fasted individuals in the morning from antecubital vein and processed as described previously [5,8]. Semi-quantitative RT-PCR was performed for determining the transcriptional expression of RAGE andEN-RAGE in PBMCs [5]. Circulating levels of sRAGE were determined in all the study subjects using commercially available enzyme-linked immunoassay as per manufacturer's instructions (DRG00, RD p=0.003, Fig. 1E). However, no significant correlation of sRAGE levels was observed with either RAGE or EN-RAGE mRNA in TA subjects. This is the first report in literature which demonstrates that mRNA levels of RAGE and its ligand EN-RAGE are up-regulated in subjects with TA. This study also demonstrates a positive correlation of RAGE and ENRAGE, in subjectswith TA for thefirst time. Our data is supported by other reports, which demonstrate that RAGE expression increases stably in certain pathological processes, and is associated with ligand-rich microenvironments [6,7]. In a previous study, we demonstrated that RAGE and EN-RAGE genes are augmented in non-diabetic CAD subjects and showed their positive correlation with the severity of disease [5]. Ligation of this receptor with its ligands activates the downstream signaling pathways such as NF-κB [10]. In addition, RAGE and EN-RAGE interactions could further induce the expression of adhesion molecules, migration and proliferation of leukocytes and augment cytokine release from the lymphocytes. Excessive expression of these genes at sites of inflammation may feasibly form a positive feedback loop that may further aggravate underlying inflammation. In corroboration to this, other reports in literature and our work have clearly demonstrated a potential participation of various cytokines, chemokines and MMPs in the pathophysiology of TA [3,8,9,11]. Significantly increased RAGE–EN-RAGE expression in TA further confirms a prevalent oxidative stress and inflammatory milieu in such a situation. Presence of various functional splice variants of RAGE is another important characteristic of this particular receptor. The production of endogenous secretory RAGE by alternative splicing may influence the actions of ligands on the full form of RAGE, located on the plasma membrane [12]. Finding increased RAGE mRNA levels in TA subjects, one