Elsy Janeth Ramos-González1, Yadira Bastian1, Julio Enrique Castañeda-Delgado1, Martin Zapata-Zúñiga2, Mariela Gómez-Moreno3, Jose Dionisio Castillo-Ortiz4, César Ramos-Remus5, José Antonio Enciso-Moreno6. 1. Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Zacatecas, México. 2. Hospital Rural No 51, IMSS Bienestar, Instituto Mexicano del Seguro Social, Villanueva, Zacatecas, México; Facultad de Medicina y Ciencias de la Salud, Universidad Autónoma de Zacatecas, Zacatecas, México. 3. Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Zacatecas, México; Departamento de Inmunología, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México. 4. Unidad de Investigación de Enfermedades Crónico-degenerativas. Guadalajara, Jalisco, México. 5. Universidad Autónoma de Guadalajara. Guadalajara, Jalisco, México. 6. Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Zacatecas, México. Electronic address: enciso_2000@yahoo.com.
Abstract
BACKGROUND: Autoantibodies have a central role in the physiopathology of Rheumatoid Arthritis (RA). However, the responsible factors that trigger and perpetuate the autoantibodies production are unknown. Toll-like receptors (TLRs) have been considered as promotors of autoantibodies production to break down the immunotolerance in RA. AIM OF THE STUDY: Evaluate the expression levels of TLR7 and TLR9 as well as their correlation with autoantibodies in first-degree relatives (FDR) of RA patients (seropositive and seronegative to ACPA), respect to early RA (eRA) and chronic RA (cRA) patients. METHODS: We selected 32 RA patients (16 as eRA and 16 as cRA) and 32 FDR of RA patients (16 seropositive and 16 seronegative to ACPA). Expression levels of TLR7 and TLR9 in whole blood samples from each group were measured by real-time PCR using total RNA extracted from each subject. Also, correlation analysis between TLRs expression and autoantibodies was performed. RESULTS: The expression of TLR7 and TLR9 was diminished in RA patients (p <0.01) but elevated in ACPA- FDR (p <0.0001) and ACPA+ FDR (p <0.05) with a positive correlation between them (r = 0.749, p <0.000). Moreover, the expression levels of TLR7 correlate positively with ACPA levels in both seropositive ACPA+ FDR subjects (r = 0.582, p = 0.018) and eRA patients (r = 0.593, p = 0.020). CONCLUSIONS: Our results showed overexpression of TLR7 and TLR9 may occur in preclinical RA subjects. TLR7 overexpression correlated with ACPA levels' production, suggesting TLR7 may play a role in ACPA development.
BACKGROUND: Autoantibodies have a central role in the physiopathology of Rheumatoid Arthritis (RA). However, the responsible factors that trigger and perpetuate the autoantibodies production are unknown. Toll-like receptors (TLRs) have been considered as promotors of autoantibodies production to break down the immunotolerance in RA. AIM OF THE STUDY: Evaluate the expression levels of TLR7 and TLR9 as well as their correlation with autoantibodies in first-degree relatives (FDR) of RA patients (seropositive and seronegative to ACPA), respect to early RA (eRA) and chronic RA (cRA) patients. METHODS: We selected 32 RA patients (16 as eRA and 16 as cRA) and 32 FDR of RA patients (16 seropositive and 16 seronegative to ACPA). Expression levels of TLR7 and TLR9 in whole blood samples from each group were measured by real-time PCR using total RNA extracted from each subject. Also, correlation analysis between TLRs expression and autoantibodies was performed. RESULTS: The expression of TLR7 and TLR9 was diminished in RA patients (p <0.01) but elevated in ACPA- FDR (p <0.0001) and ACPA+ FDR (p <0.05) with a positive correlation between them (r = 0.749, p <0.000). Moreover, the expression levels of TLR7 correlate positively with ACPA levels in both seropositive ACPA+ FDR subjects (r = 0.582, p = 0.018) and eRA patients (r = 0.593, p = 0.020). CONCLUSIONS: Our results showed overexpression of TLR7 and TLR9 may occur in preclinical RA subjects. TLR7 overexpression correlated with ACPA levels' production, suggesting TLR7 may play a role in ACPA development.