RESUMO
Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. Soluble Fas receptor (sFas) has been suggested as a Fas-mediated apoptosis blocker that could impair clonal deletion in infiltrated autoreactive cells. The FAS -670A>G promoter polymorphism has been studied in pSS. However, a relationship between FAS -670A>G promoter polymorphism and sFas levels in pSS had not been found. We examined this relationship in 77 Mexican pSS patients and 84 healthy subjects were included. Genotypes were identified by PCR-RFLP, and Fas soluble levels were quantified by ELISA. No significant differences between allele and genotype frequencies were found between these two groups. The sFas levels in the serum of pSS patients were significantly higher than in controls (9961 vs 8840 pg/mL, respectively). In addition, AA genotype carriers had significantly higher levels of sFas than GG carriers (pSS: 10,763 and 9422 pg/mL; controls: 9712 and 8305 pg/mL, respectively). An additive model analysis between genotypes (AG+GG vs AA) in both groups, demonstrated a significant association between carriers of the A allele and high sFas levels. In conclusion, carrying the double dose of A allele of FAS -670A>G polymorphism is associated with high levels of sFas in pSS, but it is not a susceptibility marker for pSS.
Assuntos
Polimorfismo Genético , Regiões Promotoras Genéticas , Síndrome de Sjogren/genética , Receptor fas/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Expressão Gênica , Frequência do Gene , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Síndrome de Sjogren/sangue , Síndrome de Sjogren/patologia , Solubilidade , Receptor fas/sangueRESUMO
OBJECTIVE: There is a lack of information about the genotype frequencies of IL-6 -174G/C and -572G/C polymorphisms in Mexicans with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the association of the IL-6 -174G/C and -572G/C polymorphisms in Mexican mestizo with RA. METHODS: We included 137 patients with RA and 102 healthy controls. Patients were assessed for clinical characteristics. IL-6 -174G/C and -572G/C polymorphisms were genotyped using PCR-RFLP analysis. Allele and genotype frequencies and the Hardy-Weinberg equilibrium were computed. Odds ratios (ORs) were computed to identify the risk for RA associated with the presence of GG genotype in comparison with the GC or CC genotypes. RESULTS: The genotype -174GG occurred at a higher frequency in cases and controls (77.4% versus 78.4%, P = 0.845). We found similar results for the genotype -572GG (54% in patients versus 60.8% in controls, P = 0.295). CONCLUSIONS: This is the first study to evaluate the association of -174G/C and -572G/C polymorphisms of the IL-6 gene with RA in Mexican mestizo patients. These two polymorphisms were not associated with RA in the studied sample. Additional studies are required to evaluate if these IL-6 polymorphisms have relevance to the development of more severe disease.
Assuntos
Artrite Reumatoide/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adulto , Alelos , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Interleucina-6/sangue , Masculino , México , Pessoa de Meia-IdadeRESUMO
To evaluate the association between pulmonary function and clinical variables in ankylosing spondylitis (AS) and to compare the pulmonary function of patients with AS with that of healthy controls, 61 AS patients and 74 healthy controls were included. In AS, we assessed clinical disease indices (BASDAI, BASFI, BASG), morning stiffness, number of hypersensitive entheses, metrology measures, 6-min walking test, acute phase reactants, radiological presence of "bamboo spine," and severity of radiological involvement in sacroiliac and vertebral joints. AS and healthy controls had similar age and gender. All the parameters of pulmonary function were significantly diminished in AS than in healthy controls (p < 0.001), with a higher proportion of restrictive pattern (57.4 vs. 5.4 %). In AS, pulmonary function correlated negatively with BASDAI, BASFI, BASG, morning stiffness, number of hypersensitive entheses, occiput-wall distance, and ESR, and positively with 6-min walking test. There was no association between pulmonary function with radiological stage of vertebral joints and sacroiliac joints, "bamboo spine," disease duration, or chest expansion. A higher frequency of AS patients had a decreased pulmonary function and results of the 6-min walking test. These abnormalities in AS were more related with disease activity than with mobility limitation.
Assuntos
Pulmão/fisiopatologia , Espondilite Anquilosante/fisiopatologia , Adulto , Antirreumáticos/uso terapêutico , Sedimentação Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Capacidade Vital , CaminhadaRESUMO
Glucocorticoids are frequently used in rheumatoid arthritis (RA) in order to alleviate symptoms of joint inflammation, retard erosions and to treat extra-articular manifestations, although these drugs may increase the risk of bone mineral loss and osteoporotic fractures. To date, in Mexico there are no studies that identify the frequency of patients with RA with corticosteroids, receiving therapy for osteoporosis. Therefore, we evaluated the prevalence and factors related to the prescription of antiresorptives in 520 Mexican patients with RA. We used a multivariate model to identify variables associated with antiresorptives prescription. We identified that although 79% of patients were under treatment with glucocorticoids, only 13% received antiresorptive agents as preventive therapy for osteoporosis. The multivariate analysis identified that higher proportions of antiresorptive drugs prescriptions were associated with female patients (OR 11.40, 95% CI: 1.5-84.3, P = 0.02), an age of 40 years or more (OR 3.22, 95% CI: 1.3-8.3, P = 0.02) and to consume a lower number of cointerventions with other drugs (OR 1.09, 95% CI: 1.0-1.2, P = 0.03). Corticosteroid treatment was not associated with the prescription of antiresorptives (P = 0.31). In conclusion, a low proportion of Mexicans with RA receive antiresorptive therapy independently regardless of whether they consume or not chronically corticosteroids. Additional strategies should be evaluated to encourage the prevention and early treatment for osteoporosis in patients with RA.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/prevenção & controle , Glucocorticoides/efeitos adversos , Osteoporose/prevenção & controle , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Comorbidade , Estudos Transversais , Quimioterapia Combinada , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/epidemiologia , Prevalência , Fatores SexuaisRESUMO
BACKGROUND: The ACTN3 gene encodes the fast muscle protein α-actinin-3. The ACTN3 R577X polymorphism is a premature stop codon and results in absence of α-actinin-3 in 577XX homozygotes. The aim of this study was to determine the ACTN3 genotype in idiopathic inflammatory myopathies (IIMs). METHODS: We performed ACTN3 genotyping on 27 patients with dermatomyositis (DM), 10 with polymyositis (PM), and 85 healthy subjects. Muscle enzyme levels of creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were recorded at the time of diagnosis and recruitment. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the allele frequency was analysed. RESULTS: A total of 36% of healthy subjects had the ACTN3 577XX polymorphism (α-actinin-3 deficiency), 18% had the 577RR (homozygous wild type) genotype, and 46% 577RX (heterozygous). In DM/PM, 70% had the ACTN3 577XX polymorphism, 6% RR, and 24% RX [odds ratio (OR) 4.12, 95% confidence interval (CI) 1.67-10.33, p < 0.001]. In healthy subjects, the R allele was present in 41% and the X allele in 59% compared to 18% and 82%, respectively, in the IIM group (OR 3.21, 95% CI 1.57-6.66, p < 0.001). Thus, the ACTN3 577X allele seemed to increase the risk of developing IIM, and DM in particular, although this was not related to severity of expression of the phenotype. CONCLUSIONS: The ACTN3 577X allele appeared to increase the risk of developing IIM; 70% of IIM patients were deficient in α-actinin-3. By contrast, ACTN3 577XX patients seemed to have less severe disease as reflected in lower muscle enzyme levels.
Assuntos
Actinina/genética , Predisposição Genética para Doença , Miosite/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Fenótipo , Índice de Gravidade de DoençaRESUMO
Rheumatoid arthritis (RA) is the prototype of the rheumatic diseases worldwide. Methotrexate (MTX) is the drug of first choice in the treatment of this disease due to its immunosuppressant effect. However, side events are present in 30% of the patients. The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are involved in the metabolism of MTX. Earlier studies reported an association between these polymorphisms and elevation of hepatic enzymes. We analyzed the frequencies of both polymorphisms and the presence of transaminasemia in 70 Mexican patients with rheumatic arthritis treated with MTX. The 19% (13/70) of patients had an increase in the serum level of transaminases. The A1298C polymorphism was associated with elevation of transaminases (P=0.024). The identification of MTHFR genotypes for C677T and A1298C polymorphisms could lead clinicians to identify patients in risk of elevation of transaminases, and give them an individualized treatment, as is a goal of pharmacogenetics.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Metotrexato/efeitos adversos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Transaminases/sangue , Antirreumáticos/farmacocinética , Artrite Reumatoide/enzimologia , Artrite Reumatoide/etnologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Frequência do Gene , Genótipo , Humanos , Metotrexato/farmacocinética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , México/epidemiologia , Razão de Chances , Farmacogenética , Fenótipo , Medicina de Precisão , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Regulação para CimaRESUMO
OBJECTIVES: Chronic liver diseases caused by hepatitis B (HBV) or C virus (HCV) are common worldwide. Despite reports on autoimmunity in viral hepatitis, studies on autoantibodies associated with systemic rheumatic diseases are inconsistent. Testing of a small number of selected autoantibody specificities using ELISA appears to be one reason for inconsistency. Sera from patients with viral hepatitis were tested by immunoprecipitation that will allow unbiased screening of autoantibodies found in systemic rheumatic diseases. METHODS: Ninety Mexican patients (37 male, 53 female, 26 HBV, 6 HBV+HCV, 58 HCV) with chronic viral hepatitis, confirmed by nested or RT-nested-PCR, HBsAg and anti-HCV antibodies, were studied. Autoantibodies were tested by immunofluorescence, immunoprecipitation and ELISA. Specificities were verified using reference sera. RESULTS: Antinuclear antibodies were found in 38% HBV, 17% HBV+HCV, and 28% in HCV. Autoantibodies to Argonaute (Ago2, Su antigen), a microRNA binding protein that plays a key role in RNA-induced silencing complex (RISC), was found in 5% (4/64) of HCV or HBV+HCV coinfected patients but not in HBV (0/26). Anti-Ago2/Su was found in 1/2 of I-IFN-treated case vs. 3/62 in cases without I-IFN. HCV did not have other lupus autoantibodies whereas 19% (5/26) of HBV had anti-U1RNP+Ku, Ro+La, RNA polymerase II, or possible U5snRNPs. CONCLUSIONS: Lupus autoantibodies were uncommon in HCV except anti-Ago2/Su. HCV and I-IFN have many ways to affect TLR signaling, miRNA and miRNA binding protein Ago2/Su. To understand the mechanism of specific targeting of Ago2 in HCV may provide a clue to understand the mechanism of specific autoantibody production.
Assuntos
Autoanticorpos/imunologia , Fator de Iniciação 2 em Eucariotos/imunologia , Hepatite B/imunologia , Hepatite C/imunologia , MicroRNAs/metabolismo , Adolescente , Adulto , Idoso , Especificidade de Anticorpos , Proteínas Argonautas , Criança , Feminino , Hepacivirus/imunologia , Hepacivirus/fisiologia , Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/sangue , Anticorpos Anti-Hepatite C/sangue , Humanos , Imunoprecipitação/métodos , Interferon Tipo I/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores Toll-Like/metabolismo , Adulto JovemRESUMO
Tumor necrosis factor-alpha (TNF-alpha) plays a central role in inflammation, and it has been directly implicated in the pathogenesis of rheumatoid arthritis (RA). TNF-alpha activity is mediated through TNFRI and TNFRII cell surface receptors, which act as physiological attenuators of TNF-alpha activity. We recruited 190 RA patients and 190 healthy subjects (HS) in order to associate the -383A>C TNFRI polymorphism with sTNFRI levels and DAS28 score in RA. In results, sTNFRI levels were higher in RA patients than HS (P = 0.04). The -383A>C TNFRI polymorphism did not show significant differences in both studied groups. However, in the RA group the sTNFRI levels were significantly elevated (P = 0.004) in A/A genotype carriers. In addition, the A/A genotype carriers had the higher DAS28 score than A/C genotype (P = 0.02). These data suggest that -383A>C TNFRI polymorphism is not a susceptibility marker in RA, whereas the increased levels of sTNFRI could reflect the clinical activity in RA patients.
Assuntos
Artrite Reumatoide/genética , Polimorfismo Genético , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/etnologia , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Fenótipo , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVE: To measure levels of soluble tumour necrosis factor alpha (TNFalpha) receptor type I (sTNFRI) and type II (sTNFRII) in order to correlate them with C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and disease activity score (DAS28) in RA patients. METHODS: We recruited 41 RA patients classified according to American College of Rheumatology (ACR) criteria and 38 healthy subjects (HS). sTNFRI and sTNFRII were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Clinical activity in RA patients was evaluated using the Disease Activity Score using 28 joint counts (DAS28). The statistical analysis was realized using SPSS version 10.0. RESULTS: Soluble TNFRI and TNFRII levels were higher in RA patients (p = 0.04 and 0.001, respectively) than HS. Serum levels of sTNFRI correlated with sTNFRII (r = 0.699, p < 0.0001). sTNFRII correlated with DAS28 (r = 0.375, p = 0.017), RF (r = 0.505, p = 0.004), and ESR (r = 0.323, p = 0.042). CONCLUSION: The increased levels of both sTNFRI and sTNFRII suggest a secondary event related to the inflammatory state observed in RA, whereas the correlation of sTNFRII with RF, ESR, and DAS28 reflects the preferential TNFRII shedding induced by TNFalpha. sTNFRII may be useful as an additional inflammatory marker in RA.
Assuntos
Artrite Reumatoide/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Índice de Gravidade de Doença , Adulto , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/sangueRESUMO
The present investigation assesses the possible role of apoptosis and necrosis in intracellular antigen exposure of kidneys from Balb/c mice. Renal tissues were cultured and treated with chemicals to induce apoptosis and /or necrosis. The expression of intracellular antigens Sm, RNP, Ro and La were monitored with antibodies against these antigens. Main results confirm that renal intracellular antigens are released and exposed onto the surface of apoptotic and necrotic cells, therefore these antigens become an easy target of autoantibodies. This mechanism may be important in the lupus nephritis pathogenesis.