Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Expression and Function of Toll Like Receptors in Peripheral Blood Mononuclear Cells of Patients with Polymyalgia Rheumatica and Giant Cell Arteritis.
Alvarez-Rodriguez4, Lorena, Lopez-Hoyos4, Marcos, Mata1, Cristina, Fontalba4, Ana, Calvo-Alen1, Jaime, Marin4, Maria Jose, Fernandez-Luna4, Jose Luis
To investigate the expression and function of the TLR family in PBMCs of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA).
We analyzed 70 patients with PMR, 20 with GCA and 24 healthy controls (HC). TLR expression was assessed by flow cytometry. TLR function was studied by stimulating PBMCs with specific ligands.
A significant increased expression of TLR7 in PBMCs of patients with active disease compared with HC was found. Despite an increased expression of TLR7, circulating monocytes from patients showed a significant lower in vitro response to TLR7 agonists. No amino acid substitutions predicted to be functionally damaging were found in TLR7. A normal response to specific TLR7 agonists in patients in complete remission eliminated a genetic defect. The expression profile on PBMCs from HC induced by plasma from PMR and GCA were marked by up-regulation of type I IFN-response transcripts, suggesting that the diminished response to TLR7 agonists in active disease was secondary to receptor saturation with natural ligands. We attempted to identify the presence of a set of respiratory virus in plasma from patients without conclusive results.
These data suggest the activation of TLR7 by a natural(s) ligand(s) in patients with PMR and GCA that is followed by a selective desensitization of the receptor. Despite the failure to identify a responsible virus in plasma from patients, the up-regulation of type I IFN-response genes after stimulation with patients' plasma suggests a possible viral etiology in these two syndromes.
To cite this abstract, please use the following information:
Alvarez-Rodriguez, Lorena, Lopez-Hoyos, Marcos, Mata, Cristina, Fontalba, Ana, Calvo-Alen, Jaime, Marin, Maria Jose, et al; Expression and Function of Toll Like Receptors in Peripheral Blood Mononuclear Cells of Patients with Polymyalgia Rheumatica and Giant Cell Arteritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1296