Sahar Mortezagholi1, Zohreh Babaloo1, Parisa Rahimzadeh2, Haideh Namdari3, Mojgan Ghaedi2, Farhad Gharibdoost4, Reza Mirzaei5, Katayoon Bidad6, Eisa Salehi5. 1. a Department of Immunology, School of Medicine , Tabriz University of Medical Sciences , Tabriz , Iran. 2. b Department of Immunology, School of Public Health , Tehran University of Medical Sciences , Tehran , Iran. 3. c Department of Immunology, School of Medicine , Shiraz University of Medical Sciences , Shiraz , Iran. 4. d Department of Rheumatology, Rheumatology Research Center , Tehran University of Medical Sciences , Tehran , Iran. 5. e Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran. 6. f Tehran University of Medical Sciences , Tehran , Iran.
Abstract
CONTEXT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by autoreactive antibodies. Recent findings revealed the importance of innate immune responses, especially Toll-like receptors (TLRs) in the pathogenesis of SLE. OBJECTIVE: In this study, the level of TLR9 expression on peripheral blood mononuclear cells (PBMCs) was analyzed. The levels of produced IFN-α were also measured in supernatant of PBMCs from SLE patients and healthy controls after stimulation with CpG ODN2216 which is a plasmocytoid dendritic cell (pDC)-specific TLR9 ligand. MATERIALS AND METHODS: TLR9 expression was analyzed by real-time polymerase chain reaction (PCR) and flow cytometry in 35 SLE patients and 38 healthy controls and IFN-α concentration was measured in supernatants using enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that the TLR9 expression in the mRNA and the protein level was significantly higher in PBMCs from SLE patients. However, IFN-α concentration in patients and controls significantly increased in response to CpG stimulation but this increase was significantly higher in healthy controls compared with SLE patients. Our results do not show any association between taking hydroxychloroquine and reduction in IFN-α production in SLE patients. DISCUSSION AND CONCLUSIONS: Regarding the findings of the study, there is the possibility that TLR9 has played a role in SLE pathogenesis, and consequently it implies that TLRs can be considered to be the therapeutic targets for systemic autoimmunity. We may conclude that PBMCs in patients are functionally impaired in response to TLR ligation via innate response stimulating pathogen-associated molecular patterns (PAMPs).
CONTEXT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by autoreactive antibodies. Recent findings revealed the importance of innate immune responses, especially Toll-like receptors (TLRs) in the pathogenesis of SLE. OBJECTIVE: In this study, the level of TLR9 expression on peripheral blood mononuclear cells (PBMCs) was analyzed. The levels of produced IFN-α were also measured in supernatant of PBMCs from SLEpatients and healthy controls after stimulation with CpG ODN2216 which is a plasmocytoid dendritic cell (pDC)-specific TLR9 ligand. MATERIALS AND METHODS:TLR9 expression was analyzed by real-time polymerase chain reaction (PCR) and flow cytometry in 35 SLEpatients and 38 healthy controls and IFN-α concentration was measured in supernatants using enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that the TLR9 expression in the mRNA and the protein level was significantly higher in PBMCs from SLEpatients. However, IFN-α concentration in patients and controls significantly increased in response to CpG stimulation but this increase was significantly higher in healthy controls compared with SLEpatients. Our results do not show any association between taking hydroxychloroquine and reduction in IFN-α production in SLEpatients. DISCUSSION AND CONCLUSIONS: Regarding the findings of the study, there is the possibility that TLR9 has played a role in SLE pathogenesis, and consequently it implies that TLRs can be considered to be the therapeutic targets for systemic autoimmunity. We may conclude that PBMCs in patients are functionally impaired in response to TLR ligation via innate response stimulating pathogen-associated molecular patterns (PAMPs).
Authors: Michael R Edwards; Rujuan Dai; Bettina Heid; Catharine Cowan; Stephen R Werre; Thomas Cecere; S Ansar Ahmed Journal: Sci Rep Date: 2020-03-23 Impact factor: 4.379
Authors: Shrouk A Mohammed; Laila M Al Kady; Ghada S Boghdadi; Ghada A Dawa; Marian A Gerges; Maher A El Shafai Journal: Int J Gen Med Date: 2022-01-18