RESUMEN
The original version of this article, unfortunately, contained errors. Figure citation, caption, image and updated sentence in the Result section are now presented correctly in this article.
RESUMEN
The "A disintegrin and metalloprotease" (ADAM) family is thought to play an important role in tissue destruction and inflammatory reactions. ADAM-17 was first described as the protease responsible for tumor necrosis factor (TNF)-α shedding. Here, we have shown the expression of ADAM-17 in inflammatory myopathy and demonstrated the role of inflammation in interstitial lung diseases (ILD). ADAM-17 in inflammatory myopathy serum [polymyositis (n = 26), dermatomyositis (n = 34), and clinically amyopathic dermatomyositis (n = 10)] and healthy control (n = 19) was measured using enzyme-linked immunosorbent assay. The relationship between ADAM-17 and clinical data was examined. Finally, we performed immunohistological analysis to investigate the expression of ADAM-17 on the muscles of the inflammatory myopathy patients. ADAM-17 in inflammatory myopathy was significantly higher than that in healthy control (mean ± SEM, 1048 ± 312 and 36 ± 18 pg/ml, respectively; p < 0.05). ADAM-17 in post-treatment with corticosteroid and/or immunosuppressant serum was significantly decreased compared with that in pre-treatment serum (1465 ± 562 and 1059 ± 503 pg/ml, respectively; p < 0.01). ADAM-17 was significantly positively correlated with fractalkine/CX3CL1 and CXCL16. In addition, ADAM-17 in inflammatory myopathy with ILD patients (n = 46) was significantly higher than that in non-ILD patients (n = 24) (1379 ± 454 and 413 ± 226 pg/ml, respectively; p < 0.05). We found the expression of ADAM-17 on muscle biopsy tissue. ADAM-17 is expressed in inflammatory myopathies especially ILD, suggesting that ADAM-17 plays a role in lung fibrosis. ADAM-17 may be a potential target in inflammatory myopathies with ILD.
Asunto(s)
Proteína ADAM17/metabolismo , Enfermedades Pulmonares Intersticiales/metabolismo , Músculo Esquelético/metabolismo , Miositis/metabolismo , Proteína ADAM17/sangre , Corticoesteroides/uso terapéutico , Quimiocina CX3CL1/sangre , Quimiocina CXCL16/sangre , Femenino , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Miositis/sangre , Miositis/tratamiento farmacológicoRESUMEN
OBJECTIVES: A disintegrin and metalloproteinase (ADAM)-10 is expressed in rheumatoid arthritis (RA). In this study, we focused on ADAM-10 as a predictive factor for the treatment with biologics in RA. METHODS: The levels of ADAM-10 and fractalkine/CX3CL1 in RA and healthy controls serum were measured using enzyme-linked immunosorbent assays. Fifteen patients were treated with adalimumab (ADA), and 20 patients were treated with tocilizumab (TCZ). RESULTS: ADAM-10 positively correlated with fractalkine/CX3CL1 in the sera of RA patients and was presented at a significantly higher level compared to that in normal serum (487 ± 80 pg/ml and 85 ± 33 pg/ml, respectively, p < 0.05). ADAM-10 highly correlates with fractalkine/CX3CL1 in the sera of RA patients. The level of ADAM-10 decreased after the treatment with TCZ but not with ADA. In addition, we found that the level of ADAM-10 in TCZ responders was significantly higher than that of the TCZ nonresponders at 24 weeks (619 ± 134 pg/ml and 109 ± 25 pg/ml, respectively). Multiple regression analysis showed that ADAM-10 was only identified as independent predictive variable for the improvement of DAS28 (ESR) at 24 weeks. CONCLUSIONS: ADAM-10 may be a predictor of the effectiveness of TCZ in treating RA.
Asunto(s)
Proteína ADAM10/sangre , Anticuerpos Monoclonales Humanizados , Artritis Reumatoide , Quimiocina CX3CL1/sangre , Quimiocina CXCL16/sangre , Adalimumab/administración & dosificación , Adalimumab/efectos adversos , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Artritis Reumatoide/sangre , Artritis Reumatoide/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Resultado del TratamientoRESUMEN
OBJECTIVE: Sex-specific medicine has attracted attention in recent years, but no report on rheumatoid arthritis (RA) has examined sex differences in the effectiveness of biologics on activities of daily living (ADL), quality of life (QOL), or depressive state. METHODS: The study subjects were 161 RA patients (female: 138; male: 23) attending regular doctor visits at our hospital. We compared the changes in disease activity, which was evaluated using the simplified disease activity index (SDAI), ADL (using the modified health assessment questionnaire; mHAQ), QOL (using short form-36; SF-36), and the Hamilton Depression Rating Scale (HAM-D) for RA patients between each sex over a six-month observation period while administering biologic treatment. RESULTS: The female patients reported significant improvements in the following metrics: SDAI: from 22.1 ± 11.9 to 8.9 ± 7.8 (p < 0.001); mHAQ: from 0.46 ± 0.50 to 0.32 ± 0.45 (p < 0.001); and HAM-D: from 6.2 ± 4.8 to 3.8 ± 4.1 (p < 0.001). Moreover, all eight items of the SF-36 were significantly improved (p < 0.01). In contrast, the male patients improved on the SDAI (from 27.9 ± 11.7 to 12.7 ± 8.6 (p < 0.001)), but we did not observe significant improvements in the mHAQ or HAM-D scores or in any items on the SF-36. CONCLUSION: Both male and female patients with RA improved when using a biological drug. Sex differences in the improvement of depressive state were observed.
RESUMEN
OBJECTIVES: The study investigated whether renal complications affected the efficacy and safety of tacrolimus combination therapy in patients with systemic lupus erythematosus (SLE) during a maintenance phase. METHODS: Fifty-seven patients with SLE (A: 30 cases with renal complication, B: 27 cases without renal complications) were included. The presence of renal complications was defined as proteinuria ≥0.5â g/day and lupus nephritis on renal biopsy. Major outcome measures included SLE disease activity index (SLEDAI), steroid dose, serum anti-dsDNA Ab, C3 and creatinine (Cr) levels and estimated glomerular filtration rate (eGFR). The patient's background factors included age, gender, disease duration and ACE-I/angiotensin II receptor blocker and statin therapies. We compared these outcome measures pre treatment and after 1â year of treatment. RESULTS: The SLEDAI and serum C3 levels improved in both groups from pretreatment period to post-treatment period: from 7.2±5.0 to 2.8±2.3 in A and 6.4±3.8 to 2.4±2.2 in B, p<0.001, and from 65.9±24.6 to 77.7±18.2â mg/dL in A and 81.8±23.0 to 90.6±19.4â mg/dL in B, p=0.002, respectively. The anti-dsDNA antibody level was reduced, and the serum Cr and eGFR levels were slightly elevated. No patients developed end-stage renal failure that required artificial dialysis. CONCLUSIONS: Tacrolimus combination therapy had additive beneficial effects on reduced proteinuria and increased serum C3 levels in patients with SLE with renal complications during a maintenance phase.
RESUMEN
A disintegrin and metalloproteases (ADAMs) are a family of proteins that have been reported to be involved in several inflammatory conditions. We examined the secretion of ADAM-10 in biological fluids from patients with rheumatoid arthritis (RA) and the role it plays in monocyte migration. ADAM-10 levels were measured using enzyme-linked immunosorbent assays and immunofluorescence. To examine the role of ADAM-10 in RA synovial fluids (SFs), we studied THP-1 (human acute monocyte leukemia cell line) and monocyte chemotaxis. To determine whether ADAM-10 plays a role in cell proliferation in the RA synovium, we assayed the proliferation of ADAM-10 small interfering RNA (siRNA)-transfected RA fibroblast-like synoviocytes (FLSs). The ADAM-10 level in RA serum was significantly higher than that in normal serum and was correlated with a disease activity score of 28. ADAM-10-depleted RA SFs showed a decrease in THP-1 and monocyte migratory activity compared with that of sham-depleted controls. ADAM-10 siRNA inhibited monocyte adhesion to RA FLSs. Finally, blocking ADAM-10 secretion in RA FLSs resulted in decreased production of fractalkine/CX3CL1 and vascular endothelial cell growth factor. These data indicate that ADAM-10 plays a role in monocyte migration in RA and suggest that targeting ADAM-10 may provide a method of decreasing inflammation and potentially treating other inflammatory diseases.
Asunto(s)
Proteínas ADAM/sangre , Secretasas de la Proteína Precursora del Amiloide/sangre , Artritis Reumatoide/sangre , Artritis Reumatoide/patología , Movimiento Celular , Proteínas de la Membrana/sangre , Monocitos/patología , Proteína ADAM10 , Adhesión Celular , Línea Celular , Quimiotaxis , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Mediadores de Inflamación/metabolismo , ARN Interferente Pequeño/metabolismo , Líquido Sinovial/metabolismoRESUMEN
OBJECTIVE: Rheumatoid arthritis (RA) patients have a greater depressive tendency than normal subjects, and infliximab is known to provide quick therapeutic effects and to have high bioavailability for RA. We therefore investigated whether the depressive state of RA patients would be improved by infliximab. MATERIAL AND METHODS: The Self-Rating Depression Scale (SDS) was used to evaluate 34 RA patients before and 14 or 30 weeks after inflixi mab treatment using the SDS and Disease Activity Score (DAS) 28. The SDS and DAS28 results before and after treatment were compared. RESULTS: We also included 42 cases treated with methotrexate as the control group. The SDS decreased in both groups, and the intraindividual vari ability was p<0.001, indicating that the drugs had significantly different effects on the SDS. The DAS tended to decrease in both groups, but the intraindividual variability was p=0.199, indicating no difference between the two drugs. CONCLUSION: This study is a preliminary study, but the data suggest that infliximab may reduce RA disease activity and improve the depressive state.