OBJECTIVE: To investigate the expression and function of the Toll-like receptor (TLR) family in peripheral blood mononuclear cells (PBMCs) of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: The authors analysed 70 patients with PMR, 20 with GCA, and 24 healthy controls (HC). TLR expression was assessed by flow cytometry. TLR function was assessed by stimulating PBMCs with specific ligands. RESULTS: A significantly increased expression of TLR7 in PBMCs of patients with active disease compared with HC was found. Despite increased expression of TLR7, circulating monocytes from patients showed a significantly 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. TLR expression and function were also affected to some degree in other diseases characterised by a strong acute phase response. CONCLUSION: These data suggest activation of TLR7 during the active phase of PMR and GCA which resolves with complete disease remission. Whether this finding is the consequence of the marked inflammatory process in these disorders or activation by natural ligands remains to be explored.
OBJECTIVE: To investigate the expression and function of the Toll-like receptor (TLR) family in peripheral blood mononuclear cells (PBMCs) of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: The authors analysed 70 patients with PMR, 20 with GCA, and 24 healthy controls (HC). TLR expression was assessed by flow cytometry. TLR function was assessed by stimulating PBMCs with specific ligands. RESULTS: A significantly increased expression of TLR7 in PBMCs of patients with active disease compared with HC was found. Despite increased expression of TLR7, circulating monocytes from patients showed a significantly 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. TLR expression and function were also affected to some degree in other diseases characterised by a strong acute phase response. CONCLUSION: These data suggest activation of TLR7 during the active phase of PMR and GCA which resolves with complete disease remission. Whether this finding is the consequence of the marked inflammatory process in these disorders or activation by natural ligands remains to be explored.
Authors: María Teresa Arias-Loste; Paula Iruzubieta; Ángela Puente; David Ramos; Carolina Santa Cruz; Ángel Estébanez; Susana Llerena; Carmen Alonso-Martín; David San Segundo; Lorena Álvarez; Antonio López Useros; Emilio Fábrega; Marcos López-Hoyos; Javier Crespo Journal: Int J Mol Sci Date: 2016-11-10 Impact factor: 5.923
Authors: María Teresa Arias-Loste; Joaquín Cabezas; Susana Llerena; Paula Iruzubieta; David San-Segundo; David Merino; Antonio Cuadrado; José Pedro Vaqué; Marcos López-Hoyos; Javier Crespo Journal: Viruses Date: 2021-04-07 Impact factor: 5.048
Authors: Yannick van Sleen; Jacoba C Graver; Wayel H Abdulahad; Kornelis S M van der Geest; Annemieke M H Boots; Maria Sandovici; Elisabeth Brouwer Journal: Front Immunol Date: 2019-08-22 Impact factor: 7.561