Association of the polymorphisms rs179008 (TLR7), rs2004640 (IRF5), rs1800795 (IL-6) and rs2280788 (CCL5) with systemic lupus erythematosus in women of Mayan ethnicity from Yucatan.

Introduction: IFN-α is the main cytokine in SLE, and single nucleotide polymorphisms (SNP) in different genes could induce it. Aim: To determine the association of rs2004640 (IRF5), rs179008 (TLR7), rs1800795 (IL-6) and rs2280788 (CCL5) with SLE in Mexican women with Mayan ethnicity. Methods: DNA and RNA were isolated from the peripheral blood of 110 patients and 200 healthy control subjects. SNP genotyping and gene expression analysis of IRF5, TLR7, IL-6 and IFN-α were determined by real-time PCR and analyzed with SNP Stat, Stata 10.1 and Graph Pad Prism v5. Results: rs2004640, rs179008, and rs1800795 in both groups were according to Hardy-Weinberg equilibrium. Risk alleles rs179008T and rs2004640T frequencies were higher in controls (p = 0.015 and p = 0.028, respectively), whereas rs179008A frequency was higher in patients (p = 0.015). Allelic combination AGT frequency was higher in patients (p = 0.001). IL-6 rs1800795C > G and CCL5 rs2280788G > C frequencies did not show significant differences (p > 0.05), being rs2280788G (CCL5) monomorphic in controls. SLE patients showed higher TLR7, IRF5, IL6, and IFN-α mRNA levels. IRF5 expression was higher in SLE patients homozygous for rs2004640T (IRF5). Conclusion: This work showed the contribution of TLR7 and IRF5 in SLE pathogenesis in Mayan females from Yucatan.

Association between fibromyalgia syndrome clinical severity and body composition. A principal component analysis / Asociación entre las manifestaciones clínicas del síndrome de fibromialgia y la composición corporal. Un análisis de componentes principales

Introduction: The type of body composition modulates the severity of some musculoskeletal conditions, in fibromyalgia syndrome (FMS), this type of association remains relatively unexplored. Objective: To analyze the association between the type of body composition and FMS using Principal Component Analysis (PCA). The FMS clinical outcome measures were: Symptom Severity Scale (SSS), Widespread Pain Index (WPI; and Fibromyalgia Impact Questionnaire (FIQ). Methods: Forty-three women with FMS (ACR 2010 criteria) were clinically and anthropometrically evaluated. The anthropometric data were integrated into two indicators using a PCA methodology (PCA-Fat and PCA-muscle). Additionally, the patients were classified into high and low categories for each clinical indicator, which were used as dependent variables in binomial logistic regression (BLR) models. Results: We found a positive correlation between PCA-Fat with WPI (r=0.326, P=.043) and FIQ (r=0.325, P=.044), and negative correlation (r=−0.384, P=.013) between PCA-muscle and SSS. In the BLR analysis, PCA-Fat was a significant predictor for high WPI (OR=2.477, P=.038); while for high SSS, PCA-muscle (OR=0.303, P=.009) was an inversely significant predictor. Conclusions: The results suggest that the volume of fat mass can negatively modulate the severity of FMS. We propose that the evaluation of body composition should be a basic element for the clinical approach of patients with FMS.(AU)

Introducción: El tipo de composición corporal modula la gravedad de algunos padecimientos musculoesqueléticos; en el síndrome de fibromialgia (SFM) este tipo de asociación permanece relativamente inexplorado. Objetivo: Mediante análisis de componentes principales (PCA), analizar la asociación entre el tipo de composición corporal y medidas de desenlace clínico del SFM, como la Escala de Gravedad de Síntomas, el Índice de Dolor Generalizado y el Cuestionario de Impacto de la Fibromialgia. Métodos: Cuarenta y tres mujeres con SFM (criterios ACR 2010) fueron evaluadas clínica y antropométricamente. Los datos antropométricos se integraron en 2 indicadores mediante una metodología de PCA (PCA-Fat y PCA-Muscle). Adicionalmente, las pacientes se clasificaron en categorías alta y baja para cada indicador clínico, los cuales se utilizaron como variables dependientes en modelos de regresión logística binomial. Resultados: Encontramos correlación positiva entre PCA-Fat, el Índice de Dolor Generalizado (r=0,326, p=0,043) y el Cuestionario de Impacto de la Fibromialgia (r=0,325, p=0,044), y correlación negativa (r=−0,384, p=0,013) entre PCA-Muscle y la Escala de Gravedad de Síntomas. En el modelo de regresión logística binomial, PCA-Fat fue un predictor significativo para un Índice de Dolor Generalizado alto (OR=2,477, p=0,038), mientras que para una Escala de Gravedad de Síntomas alta, PCA-Muscle (OR=0,303, p=0,009) fue un predictor inversamente significativo. Conclusiones: Los resultados evidencian que el volumen de masa grasa puede modular negativamente la gravedad del SFM. Proponemos que la evaluación de la composición corporal debe ser un elemento básico para el abordaje clínico de los pacientes con SFM.(AU)

Association between fibromyalgia syndrome clinical severity and body composition. A principal component analysis.

INTRODUCTION: The type of body composition modulates the severity of some musculoskeletal conditions, in fibromyalgia syndrome (FMS), this type of association remains relatively unexplored. OBJECTIVE: To analyze the association between the type of body composition and FMS using Principal Component Analysis (PCA). The FMS clinical outcome measures were: Symptom Severity Scale (SSS), Widespread Pain Index (WPI; and Fibromyalgia Impact Questionnaire (FIQ). METHODS: Forty-three women with FMS (ACR 2010 criteria) were clinically and anthropometrically evaluated. The anthropometric data were integrated into two indicators using a PCA methodology (PCA-Fat and PCA-muscle). Additionally, the patients were classified into high and low categories for each clinical indicator, which were used as dependent variables in binomial logistic regression (BLR) models. RESULTS: We found a positive correlation between PCA-Fat with WPI (r=0.326, P=.043) and FIQ (r=0.325, P=.044), and negative correlation (r=-0.384, P=.013) between PCA-muscle and SSS. In the BLR analysis, PCA-Fat was a significant predictor for high WPI (OR=2.477, P=.038); while for high SSS, PCA-muscle (OR=0.303, P=.009) was an inversely significant predictor. CONCLUSIONS: The results suggest that the volume of fat mass can negatively modulate the severity of FMS. We propose that the evaluation of body composition should be a basic element for the clinical approach of patients with FMS.

Copy Number Variation and Frequency of rs179008 in TLR7 Gene Associated with Systemic Lupus Erythematosus in Two Mexican Populations.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which genetic factors play a role in the susceptibility to develop it. Genes related to the synthesis of interferons such as TLR7 and genetics factors such as single nucleotide polymorphisms (SNPs) or copies number variation (CNV) in the gene have been involved with the development of the disease. The genetic differences between the populations contribute to the complexity of LES. Mexico has a mestizo population with a genetic load of at least three origins: Amerindian, Caucasian, and African. The mestizo of Yucatán is the only group whose contribution Amerindian is mainly Mayan, geographically distant from other Mexican Amerindians. We analyzed the CNV and the frequency of SNP rs179008 of the TLR7 as genetic risk factors in developing the disease in patients from Yucatán and Central Mexico. Results show that 14% of the cases of the Yucatecan population showed significantly >2 CNV and a higher risk of developing the disease (OR: 34.364), concerning 4% of those coming from Central Mexico (OR: 10.855). T allele and the A/T and T/T risk genotypes of rs179008 were more frequent in patients of Central Mexico than in those of Yucatán (50% vs. 30%, 93% vs. 30%, 4% vs. 1%), and association with susceptibility to develop SLE was observed (OR: 1.5 vs. 0.58, 9.54 vs. 0.66, 12 vs. 0.14). Data support the genetic differences between and within Mexican mestizo populations and the role of the TLR7 in the pathogenesis of SLE.

Serological and molecular analysis of parvovirus B19 infection in Mayan women with systemic lupus erythematosus in Mexico.

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that mainly affects women, characterized by the production of autoantibodies. Its causal agent is unknown, but the combination of environmental, hormonal and genetic factors may favor the development of the disease. Parvovirus B19 has been associated with the development of SLE, since it induces the production of anti-single stranded DNA antibodies. It is unknown whether PV-B19 infection is an environmental factor that trigger or reactivate SLE in the Mexican Mayan population. AIM: A preliminary serological and molecular study of PV-B19 infection in Mayan women with established SLE was done. METHODS: IgG and IgM anti PV-B19 were evaluated in 66 SLE patients and 66 control subjects, all women of Mayan origin. Viral DNA and viral load were analyzed by qPCR. RESULTS: Insignificant levels of IgM were observed in 14.3% (4/28) of the patients and 11.4% (4/35) of control subjects. IgG was detected in 82.1% (23/28) of the patients and 82.9% (29/35) of control subjects, but were significantly higher in patients. Viral DNA was found in 86.0% (57/66) of the patients and 81.0% (54/66) of control subjects. Viral load, quantified in 28/66 patients and 31/66 controls which were positive for IgM and IgG, was significantly higher in controls. CONCLUSION: The high prevalence of PV-B19 in Yucatan, and the presence of IgM, IgG, and viral load in Mayan women with established SLE suggest that PV-B19 infection could be an environmental factor to trigger or reactivate SLE.

ANTECEDENTES: Lupus eritematoso sistémico (LES) es una enfermedad sistemica autoinmune que afecta principalmente a las mujeres, caracterizada por la producción de autoanticuerpos. El agente causaal es desconocido. Pero la combinación de factores ambientales, hormonales y genéticos podría favorecer el desarrollo de la enfermedad. El parvovirus B19 se asoció con el desarrollo de LES, debido a que induce la producción de anticuerpos anti-cadena simple de DNA. Es desconocido si la infección PV-B19 es un factor ambiental que desencadena o reactiva LES en la población mexicana Maya. OBJETIVO: Se realizó un estudio serológico y molecular preliminar de la infección de PV-B19 en mujeres Mayas con LES. MÉTODOS: Se evaluó IgG and IgM anti PV-B19 en 66 pacientes con LES y 66 controles sanos, todas las mujeres fueron de origen Maya. DNAViral y la carga viral fueron analizadas por qPCR. RESULTADOS: Se determinaron niveles insignificantes de IgM en el 14.3% (4/28) de las pacientes y en el 11.4% (4/35) de los controles. IgG se detectó en el 82.1% (23/28) de los pacients y en el 82.9% (29/35) de los controles. Hubo un alta significancia en los pacientes con LES. DNA viral se encontró en el 86.0% (57/66) de los pacientes y en el 81.0% (54/66) de los controles. La carga viral se cuantifico en 28/66 pacientes y en 31/66 de los controles, la cual fueron positivos para IgM e IgG; fue significativamente mas alta en los controles. CONCLUSIÓN: La alta prevalencia de PV-B19 en Yucatan y la presencia de IgM, IgG y una carga viral en mujeres Mayas con LES sugiere que la infección con PV-B19 poria ser un factor ambiental que desencadene o reactive el LES.

Serological and molecular analysis of parvovirus B19 infection in Mayan women with systemic lupus erythematosus in Mexico / Análisis serológico y molecular de la infección por parvovirus B19 en mujeres mayas con lupus eritematoso sistémico en México

Abstract Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that mainly affects women, characterized by the production of autoantibodies. Its causal agent is unknown, but the combination of environmental, hormonal and genetic factors may favor the development of the disease. Parvovirus B19 has been associated with the development of SLE, since it induces the production of anti-single stranded DNA antibodies. It is unknown whether PV-B19 infection is an environmental factor that trigger or reactivate SLE in the Mexican Mayan population. Aim: A preliminary serological and molecular study of PV-B19 infection in Mayan women with established SLE was done. Methods: IgG and IgM anti PV-B19 were evaluated in 66 SLE patients and 66 control subjects, all women of Mayan origin. Viral DNA and viral load were analyzed by qPCR. Results: Insignificant levels of IgM were observed in 14.3% (4/28) of the patients and 11.4% (4/35) of control subjects. IgG was detected in 82.1% (23/28) of the patients and 82.9% (29/35) of control subjects, but were significantly higher in patients. Viral DNA was found in 86.0% (57/66) of the patients and 81.0% (54/66) of control subjects. Viral load, quantified in 28/66 patients and 31/66 controls which were positive for IgM and IgG, was significantly higher in controls. Conclusion: The high prevalence of PV-B19 in Yucatan, and the presence of IgM, IgG, and viral load in Mayan women with established SLE suggest that PV-B19 infection could be an environmental factor to trigger or reactivate SLE.

Resumen Antecedentes: Lupus eritematoso sistémico (LES) es una enfermedad sistemica autoinmune que afecta principalmente a las mujeres, caracterizada por la producción de autoanticuerpos. El agente causaal es desconocido. Pero la combinación de factores ambientales, hormonales y genéticos podría favorecer el desarrollo de la enfermedad. El parvovirus B19 se asoció con el desarrollo de LES, debido a que induce la producción de anticuerpos anti-cadena simple de DNA. Es desconocido si la infección PV-B19 es un factor ambiental que desencadena o reactiva LES en la población mexicana Maya. Objetivo: Se realizó un estudio serológico y molecular preliminar de la infección de PV-B19 en mujeres Mayas con LES. Métodos: Se evaluó IgG and IgM anti PV-B19 en 66 pacientes con LES y 66 controles sanos, todas las mujeres fueron de origen Maya. DNAViral y la carga viral fueron analizadas por qPCR. Resultados: Se determinaron niveles insignificantes de IgM en el 14.3% (4/28) de las pacientes y en el 11.4% (4/35) de los controles. IgG se detectó en el 82.1% (23/28) de los pacients y en el 82.9% (29/35) de los controles. Hubo un alta significancia en los pacientes con LES. DNA viral se encontró en el 86.0% (57/66) de los pacientes y en el 81.0% (54/66) de los controles. La carga viral se cuantifico en 28/66 pacientes y en 31/66 de los controles, la cual fueron positivos para IgM e IgG; fue significativamente mas alta en los controles. Conclusión: La alta prevalencia de PV-B19 en Yucatan y la presencia de IgM, IgG y una carga viral en mujeres Mayas con LES sugiere que la infección con PV-B19 poria ser un factor ambiental que desencadene o reactive el LES

Expression of TLR-7, MyD88, NF-kB, and INF-α in B Lymphocytes of Mayan Women with Systemic Lupus Erythematosus in Mexico.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease involving multiple organs. It is currently accepted that several genetic, environmental, and hormonal factors are contributing to its development. Innate immunity may have a great influence in autoimmunity through Toll-like receptors. TLR-7 recognizing single-strand RNA has been involved in SLE. Its activation induces intracellular signal with attraction of MyD88 and NF-kBp65, leading to IFN-α synthesis which correlate with disease activity. OBJECTIVE: To assess the expression of TLR-7, MyD88, and NF-kBp65 in B lymphocytes of Mayan women with SLE. METHODS: One hundred patients with SLE and 100 healthy controls, all of them Mayan women, were included. TLR-7 was analyzed on B and T lymphocytes, and MyD88 and NF-kB only in B lymphocytes. Serum INF-α level was evaluated by ELISA. RESULTS: Significant expression (p < 0.0001) of TLR-7 in B and T lymphocytes and serum IFN-α increased (p = 0.034) was observed in patients. MyD88 and NF-kBp65 were also increased in B lymphocytes of patients. TLR-7 and NF-kBp65 expression correlated, but no correlation with INF-α and disease activity was detected. CONCLUSION: Data support the role of TLR-7 and signal proteins in the pathogenesis of SLE in the Mayan population of Yucatán.

Copy Number Variation of TLR-7 Gene and its Association with the Development of Systemic Lupus Erythematosus in Female Patients from Yucatan Mexico.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies against self-antigens, which occurs most often in women between 15 and 40 years of age. The innate immunity is involved in the pathogenesis of SLE through TLR- 7. Genetic factors such as copy number variation (CNV) of target genes may contribute to disease development, but this possible risk has not yet been studied in SLE patients from Yucatan, Mexico. The CNV of TLR-7 gene was determined by quantitative polymerase chain reaction assay using TaqMan probes in 80 SLE women and 150 control subjects. The results showed that 10% of SLE patients exhibited more than two copies of TLR-7 gene, whereas no mRNA overexpression was detected. These data suggested that increased CNV of the TLR-7 gene in Yucatan SLE women can be a risk factor for this disease.