RESUMEN
OBJECTIVE: The objective of this study is to investigate the expression levels of Th9 CD4+ T cells and IL-9 secretion in peripheral blood mononuclear cells of patients with primary Sjogren's syndrome. Further, this study aimed to investigate the role of Th9 cells in the occurrence and development of pSS. METHODS: A total of 20 pSS patients and 20 healthy people, matched with age and gender, were selected as the experimental and control group, respectively. Flow cytometry and ELISA were used to detect the expression of Th9 cytokines in peripheral blood mononuclear cells and IL-9 in serum, respectively. These factors were then correlated to other clinical indicators. RESULTS: The levels of Th9 CD4+ T cells and IL-9 of pSS patients were significantly higher than those of the control group. Th9 CD4+ T cells and IL-9 levels in peripheral blood of pSS patients were negatively correlated with salivary flow rate, while IL-9 level was positively correlated with globulin. The transcription levels of IL-9 and immune-related genes including IL-4, IL-7, IL-17, SMAD3, STAT5 and JAK3 were dramatically increased in serum of pSS patients. CONCLUSION: The expression levels of Th9 in peripheral blood and serum IL-9 of patients with pSS were significantly increased, which were correlated with clinical immunological indexes. Together, these data suggest that Th9 cells and IL-9 may be involved in the pathogenesis of pSS.
Asunto(s)
Síndrome de Sjögren , Linfocitos T , Linfocitos T CD4-Positivos , Humanos , Interleucina-9/genética , Leucocitos Mononucleares , Síndrome de Sjögren/genéticaRESUMEN
BACKGROUND: The systemic immune-inflammation index (SII) is a recently developed indicator for systemic inflammatory response. We aimed to explore the association between SII and disease activity in patients with ankylosing spondylitis (AS). METHODS: This retrospective study included 136 patients with AS and 63 healthy controls. Patients were divided into two groups according to Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); active group (n = 60) and remission group (n = 76). Clinical, laboratory, and demographic characteristics were recorded. Spearman's correlation analysis was used to determine correlations of SII with C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and BASDAI in AS patients. Binary logistic regression analysis was used to assess risk factors for AS disease activity. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of SII and the above variables for the active group compared with the remission group. RESULTS: Systemic immune-inflammation index levels were higher in AS patients than in healthy controls (p < 0.001). SII levels were higher in the active group than in the remission group (p < 0.001). For patients with AS, SII correlated positively with CRP (rs = 0.483, p < 0.001), ESR (rs = 0.374, p < 0.001), and BASDAI (rs = 0.667, p < 0.001). SII (OR = 1.009, 95% CI = 1.006-1.012, p < 0.001) was an independent risk factor affecting AS disease activity. The specificity and sensitivity of SII using a cutoff value of 513.2 were 83.33% and 86.84%, respectively, for the active group. CONCLUSION: Systemic immune-inflammation index was increased in AS. SII may be a novel indicator for monitoring AS disease activity.
Asunto(s)
Proteína C-Reactiva/metabolismo , Inflamación/fisiopatología , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/patología , Adulto , Sedimentación Sanguínea , Estudios de Casos y Controles , China/epidemiología , Femenino , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Masculino , Pronóstico , Curva ROC , Estudios Retrospectivos , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/inmunología , Espondilitis Anquilosante/metabolismoRESUMEN
OBJECTIVE: To explore the prevalence and characteristics of main organ involvement in adult patients with polymyositis (PM) or dermatomyositis (DM) and determine their specific relative factors. METHODS: Using unified questionnaire, we retrospectively collected the medical records of 1 387 confirmed adult PM/DM patients from 2007 to 2012 at 22 rheumatology centers in China. Statistical analyses were performed with chi-square or Fisher exact test and multivariate analyses with logistic regression. RESULTS: A total of 1 387 patients were collected with 460 (33.2%) PM and 927 (66.8%) DM. The female:male ratio was 2.4: 1. Their onset age was ( 47 ± 14) years. A total of 1 031 (74.3%) patients had organ involvement. The prevalence of pulmonary involvement, arthritis, gastrointestinal and cardiac involvement were 44.6%, 32.3%, 21.9% and 20.3% respectively. The multivariate analysis indicated that older onset age (P < 0.01) was positively associated with pulmonary involvement while myalgia (P < 0.05) was negatively associated. Fever (P < 0.05), weight loss (P < 0.05) and Raynaud's phenomenon (P < 0.01) were positively associated with arthritis while muscle weakness (P < 0.05) negatively associated. Weight loss (P < 0.05), Raynaud's phenomenon (P < 0.01) and muscle weakness (P < 0.05) were positively associated with gastrointestinal involvement. Weight loss (P < 0.05) and swollen limbs (P < 0.05) were positively associated with cardiac involvement. CONCLUSION: The prevalence of organ involvement is high in adult PM/DM patients. Our study may aid the diagnosis of organ damage in PM/DM patients.
Asunto(s)
Dermatomiositis/patología , Polimiositis/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. METHODS: We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than - 15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics. RESULTS: In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were - 4.6% and the lower limit of one-sided 97.5% confidence interval was - 14.29%, not less than the lower limit of the non-inferiority margin (- 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference - 4.6%, 95% CI - 14.29% to 5.12%) and PPS (difference - 3.3%, 95% CI - 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab. CONCLUSIONS: Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab. TRIAL REGISTRATION NUMBER: NCT03478111.
RESUMEN
INTRODUCTION: This phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade®) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy. METHODS: Patients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity. RESULTS: A total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62-68.20%) and 56.89% for the INF group (95% CI 50.90-62.74%). The difference between the two groups was 5.65% with a 95% CI of - 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable. CONCLUSIONS: GB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF.
RESUMEN
BACKGROUND: The pathogenesis of idiopathic inflammatory myopathy (IIM) is complex and unclear. The purpose of this study was to investigate whether the noncanonical pathway of pyroptosis is involved in the pathogenesis of IIM, and the intervention effect of drugs glyburide and bright blue G (BBG). METHODS: After the drug intervention, we detected the expression of the caspase-4, caspase-5, caspase-11, GSDMD, pannexin-1, NLRP3 and P2X7R proteins in skeletal muscle tissues from the six groups using Western blotting. We detected the expression of the caspase-11, GSDMD, pannexin-1, NLRP3 and P2X7R mRNAs in skeletal muscle tissues from the six groups using RT-qPCR and detected the serum IL-18 and IL-1ß levels in the six groups using ELISAs. RESULT: Lower expression levels of the P2X7R and NLRP3 proteins were observed in the EAM + BBG group than in the EAM1 group (P < 0.05). The expression of NLRP3 in the EAM + glyburide group was lower than in the EAM2 group (P < 0.05). Lower expression levels of the P2X7R and NLRP3 mRNAs were detected in the EAM + BBG group than in the EAM1 group (P < 0.05). NLRP3 was expressed at lower levels in the EAM + glyburide group than in the EAM2 group (P < 0.05). Lower serum IL-1ß levels were detected in the EAM + BBG group than in the EAM1 group (P < 0.05), and serum IL-1ß and IL-18 levels in the EAM + glyburide group were lower than those in the EAM2 group (P < 0.05). CONCLUSION: Our results suggest that the noncanonical pathway of pyroptosis may be involved in the pathogenesis of IIM, and glyburide and BBG exert certain intervention effects on its pathogenesis.
Asunto(s)
Gliburida/farmacología , Miositis/tratamiento farmacológico , Piroptosis/inmunología , Colorantes de Rosanilina/farmacología , Animales , Modelos Animales de Enfermedad , Femenino , Gliburida/uso terapéutico , Cobayas , Humanos , Ratones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/inmunología , Músculo Esquelético/patología , Miositis/inmunología , Miositis/patología , Piroptosis/efectos de los fármacos , Colorantes de Rosanilina/uso terapéuticoRESUMEN
AIMS: To investigate the role of Slit2 and Robo1 during the vascular disease of Polymyositis (PM) / dermatomyositis (DM). BACKGROUND: PM and DM are nonsuppurative inflammatory myopathies that mainly invade the skeletal muscles. OBJECTIVE: This study attempted to explore the specific mechanism of Slit2/Robo1 signaling pathway proteins during the vascular disease of PM/DM. METHODS: The mRNA expressions of Slit2 and Robo1 in the muscle tissue were detected by RT-qPCR between newly-diagnosed PM/DM patients and healthy controls. The number of Slit2 and Robo1 positive cells in the serial sections of muscle paraffin tissues was measured by immunohistochemistry in 10 patients with PM, 10 patients with DM and 20 healthy controls. RESULTS: The study results revealed that the mRNA expressions of Slit2 and Robo1 in muscle tissue in the PM and DM groups were higher than that in the control group (P<0.05). The positive expression rates of Slit2 and Robo1 in muscle tissue in the PM and DM groups were 80.0%, 80.0%, 70.0% and 70.0%, respectively. The difference was statistically significant (P<0.001), when compared to the control group (the positive expression rates were 0% and 10%, respectively). CONCLUSION: The activation of the Slit2/Robo1 signaling pathway is an important mechanism leading to the development of PM/DM.
Asunto(s)
Dermatomiositis/patología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Polimiositis/patología , Receptores Inmunológicos/metabolismo , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , China/epidemiología , Dermatomiositis/epidemiología , Dermatomiositis/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimiositis/epidemiología , Polimiositis/metabolismo , Transducción de Señal , Adulto Joven , Proteínas RoundaboutRESUMEN
This study aims to explore the roles of cysteine-rich protein 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN2) and vascular endothelial growth factor (VEGF) in the vascular process of polymyositis (PM)/dermatomyositis (DM).Real-time quantitative polymerase chain reaction was used to determine the mRNA expression of Cyr61, CTGF, and VEGF in muscle tissues of initially treated PM/DM patients and controls. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of Cyr61, CTGF, and VEGF of initially treated PM/DM patients before and after treatment. Data were statistically analyzed using statistical software SPSS 17.0.The mRNA expression levels of Cyr61, CTGF, and VEGF in muscle tissues were higher in the PM and DM groups than in the control group (Pâ<â.05). Differences in the mRNA expression levels of Cyr61, CTGF, and VEGF in muscle tissues between the PM and DM groups were not statistically significant (Pâ>â.05). Before treatment, the serum levels of Cyr61, CTGF, and VEGF were higher in the PM and DM groups than in the control group (Pâ<â.05). Furthermore, in the PM and DM groups, the expression levels of Cyr61, CTGF, and VEGF in serum at 6 months after treatment were lower than those before treatment (Pâ<â.05).Cyr61, CTGF, and VEGF are involved in the pathogenesis of PM/DM. These may be involved in the pathogenesis mainly by affecting the formation of blood vessels and promoting inflammatory response. This suggests that microvascular lesions play an important role in the immune pathogenesis of inflammatory myopathy PM/DM.
Asunto(s)
Factor de Crecimiento del Tejido Conjuntivo/genética , Proteína 61 Rica en Cisteína/genética , Dermatomiositis/genética , Polimiositis/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Factor de Crecimiento del Tejido Conjuntivo/sangre , Proteína 61 Rica en Cisteína/sangre , Dermatomiositis/sangre , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimiositis/tratamiento farmacológico , Polimiositis/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto JovenRESUMEN
AIM: Chronic mountain sickness (CMS) is characterized by excessive erythrocytosis, and angiogenesis may be involved in the pathogenesis of this disease. The bone marrow niche is the primary site of erythropoiesis and angiogenesis. This study was aimed at investigating the associations of the levels of hypoxia-inducible factors (HIFs), erythropoietin (EPO), and erythropoietin receptor (EPOR), as well as microvessel density (MVD) in the bone marrow with CMS. RESULTS: A total of 34 patients with CMS and 30 control subjects residing in areas at altitudes of 3000-4500 m were recruited for this study. The mRNA and protein expression of HIF-2α and EPO in the bone marrow cells was significantly higher in the CMS patients than in the controls. Moreover, changes in HIF-2α expression in CMS patients were significantly correlated with EPO and hemoglobin levels. In contrast, the expression of mRNA and protein expression of HIF-1α and EPOR did not differ significantly between the CMS and control patients. Increased MVD was observed in the bone marrow of the patients with CMS and it was significantly correlated with hemoglobin. CONCLUSIONS: Bone marrow cells of CMS patients may show enhanced activity of the HIF-2α/EPO pathway, and EPO may regulate the erythropoiesis and vasculogenesis through autocrine or/and paracrine mechanisms in the bone marrow niche. The increased MVD in the bone marrow of CMS patients appears to be involved in the pathogenesis of this disease.
Asunto(s)
Mal de Altura/sangre , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/sangre , Médula Ósea/metabolismo , Eritropoyetina/sangre , Microvasos/patología , Policitemia/sangre , Adulto , Altitud , Mal de Altura/complicaciones , Médula Ósea/irrigación sanguínea , Estudios de Casos y Controles , Enfermedad Crónica , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica , Policitemia/etiología , ARN Mensajero/sangre , Transducción de SeñalRESUMEN
OBJECTIVE: To observe the expressions of caspase-8 and caspase-9 mRNA, and explore the changes of apoptosis of bone marrow hematopoietic cells in patients with chronic mountain sickness (CMS). METHODS: Of 18 CMS patients and 16 controls were enrolled in this study. The apoptotic index (AI) of bone marrow mononuclear cells (BMMNC) was measured by TUNEL technique, the levels of caspase-8 and caspase-9 mRNA in BMMNC of CMS patients and controls were determined by RT-PCR. Results (1)The AI of BMMNC in patients with CMS (8.51 ± 3.35)% was lower than that in controls (16.00 ± 4.28)% (P < 0.01); (2) The values of caspase-8 and caspase-9 mRNA were (0.28 ± 0.07) and (0.23 ± 0.08) respectively, in CMS patients, which were significantly lower than those of (0.45 ± 0.09) and (0.41 ± 0.09) respectively, in the controls (both P < 0.01); (3) Hemoglobin (Hb) value was negatively correlated with levels of caspase-8 and caspase-9 mRNA (r values were -0.52 and -0.61 respectively, both P < 0.05) in CMS patients. There was a negative correlation between AI and Hb (r value was -0.89, P < 0.01) in CMS patients. However, the significant relationship was not found between AI and level of caspase-8 or caspase-9 mRNA (P > 0.05). CONCLUSIONS: The results showed a decrease apoptosis of BMMNCs and reduced levels of caspase-8 and caspase-9 mRNA in CMS patients, the latter might be involved in the change of BMMNCs apoptosis.
Asunto(s)
Mal de Altura/metabolismo , Apoptosis , Células de la Médula Ósea/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Adulto , Mal de Altura/patología , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIM: The clinical manifestation of chronic mountain sickness (CMS) is polycythemia, pulmonary hypertension and mionectic blood. However, the pathogenesis of it is not identified now. So it is necessary to investigate the effects of the angiogenic growth factors on the pathophysiologic development of CMS. METHODS: The serum levels of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) in 13 healthy Tibetan natives (Native), 17 healthy people in Xining (control group) and 35 CMS patients were determined by quantitative sandwich enzyme immunoassay. Meanwhile, the levels of Hb, Hct and SaO2 were determined. RESULTS: The serum levels of bFGF (107.26 +/- 7.86) ng/L, PDGF (630.18 +/- 9.89) ng/L and VEGF (543.74 +/- 6.76) ng/L in CMS were significantly higher than those in Natives (37.01 +/- 9.16; 292.16 +/- 6.88; 125.51 +/- 7.26) ng/L, and in control group (40.58 +/- 5.34; 287.68 +/- 8.33; 76.26 +/- 4.60) ng/L, respectively (P < 0.01). There was no difference between the natives and the control group in bFGF and PDGF (P > 0.05), while there was predominant difference between the Natives and the control group in VEGF (P < 0.01). There was a predominant positive correlation between the serum levels of bFGF, PDGF or VEGF and hemoglobin concentrations in CMS respectively (P < 0.01). And there were positive relations between angiogenic growth factors each other. CONCLUSION: The serum levels of bFGF, PDGF and VEGF in patients with CMS significantly increase, these angiogenic growth factors may play important role on the pathophysiologic development of CMS; the VEGF level likely contributes to the adaptation to plateau hypoxia in healthy Tibetan natives; the elevated bFGF, PDGF and VEGF levels are likely associated with excessive erythropoiesis in CMS.