RESUMEN
OBJECTIVE: To investigate the role of albumin-to-globulin ratio (AGR) in systemic lupus erythematosus (SLE) and its relationship with disease activity. METHODS: This retrospective study consecutively selected patients with SLE and healthy controls. Patients were divided into three groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K): group 1 (mild disease activity, SLEDAI-2K ≤ 6), group 2 (moderate disease activity, SLEDAI-2K 7-12) and group 3 (severe disease activity, SLEDAI-2K > 12). Predictors of SLE disease activity were analysed by ordinal logistical regression. RESULTS: A total of 101 Chinese patients with SLE and 75 healthy Chinese controls were included. Patients with SLE had lower AGR values than healthy individuals, and group 3 patients with SLE displayed lower AGR values than those in group 1, but similar values to group 2. AGR was inversely correlated with SLEDAI-2K (r = -0.543). Ordinal logistic regression analysis showed that lower AGR (ß = -1.319) and lower complement C4 (ß = -1.073) were independent risk factors for SLE disease activity. CONCLUSIONS: AGR was decreased in patients with SLE and may be utilized as a useful inflammatory biomarker for monitoring SLE disease activity.
Asunto(s)
Lupus Eritematoso Sistémico , Albúmina Sérica , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Estudios de Casos y Controles , Complemento C4/metabolismo , Complemento C4/análisis , Modelos Logísticos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Seroglobulinas/análisis , Seroglobulinas/metabolismo , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: If a large amount of urate crystals is deposited in a joint cavity for an extended period of time, bone erosion will occur and gradually cause skeletal muscle necrosis and joint deformity. The aim of this study was to describe the clinical characteristics and factors associated with bone erosion in gout patients with tophi. METHODS: A total of 210 gout patients with tophi were enrolled and divided into a bone erosion group (n = 135) and a non-bone erosion group (n = 75). Digital radiography (DR) was performed to detect bone erosion in the elbow, wrist, knee, ankle joints, interphalangeal and metatarsophalangeal joints. The clinical characteristics were recorded and compared between the two groups. Multivariate logistic regression analysis was conducted to explore the factors associated with bone erosion. RESULTS: Compared with the non-bone erosion group, the bone erosion group had an older age, longer disease duration of gout and tophi, higher level of serum creatinine (sCr), higher proportion of drinking history and ulceration, and a lower glomerular filtration rate (GFR). Univariate logistic regression analysis results showed that sex, age, body mass index (BMI), gout duration, tophi duration, GFR, white blood cell (WBC) count, sCr level, smoking history, drinking history, and presence of ulceration were associated with bone destruction. Multivariable logistic regression analysis results indicated that tophi duration, drinking history, ulceration and sCr were positively and independently related to bone erosion. CONCLUSIONS: Tophi patients with bone erosion presented different clinical characteristics. Tophi duration, drinking history, ulceration and sCr were associated with bone erosion in gout patients with tophi.
Asunto(s)
Gota , Humanos , Gota/complicaciones , Factores de Riesgo , Fumar/efectos adversos , Índice de Masa Corporal , Tasa de Filtración GlomerularRESUMEN
OBJECTIVE: To identify the long non-coding RNA (lncRNA) expression profiling in exosomes derived from synovial fluid of rheumatoid arthritis (RA) patients, and carry out bioinformatics analysis on target genes of differentially expressed lncRNAs. METHODS: Exosomes were isolated from synovial fluid via ultracentrifugation. RNAs were extracted from exosomes by using HiPure Liquid RNA/miRNA kits, followed by lncRNA sequencing. Differentially expressed lncRNAs in RA were screened, and bioinformatics analysis of their target genes was carried out. qRT-PCR was used to verify the lncRNA expression levels. RESULTS: Compared with osteoarthritis (OA), 347 lncRNAs were found differentially expressed in RA. Compared with gout, 805 lncRNAs were found differentially expressed in RA. Compared with both OA and gout, 85 lncRNAs were found specially expressed in RA (65 were upregulated (including ENST00000433825.1)). Functional analysis of target genes of the specially expressed lncRNAs revealed significant enrichment of "autophagy" and "mTOR signaling pathway". The qRT-PCR results indicated that ENST00000433825.1 was highly expressed in RA, compared with both OA and gout (P < 0.05), which matched the lncRNA sequencing results. Correlation analysis showed that the level of ENST00000433825.1 in RA patients was significantly and positively correlated with the level of C-reactive protein (CRP) (P < 0.001). CONCLUSIONS: The lncRNA expression profiling in exosomes derived from synovial fluid of RA was significantly different from OA and gout. ENST00000433825.1 was highly and uniquely expressed in RA and significantly and positively correlated with CRP, which might provide a diagnostic and therapeutic biomarker for RA.
Asunto(s)
Artritis Reumatoide , Exosomas , Gota , Osteoartritis , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Líquido Sinovial/metabolismo , Exosomas/genética , Exosomas/metabolismo , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismoRESUMEN
OBJECTIVES: Our study profiled the CD4 + T-cell-derived exosomes from patients with rheumatoid arthritis (RA) using proteomics. METHODS: Proteomic analysis of CD4 + T-cell-derived exosomes was performed by tandem mass tags (TMT) combined with LC-MS/MS. We validated the most significantly upregulated and downregulated proteins using ELISA and WB. RESULTS: The proteomic results showed that there were 3 upregulated differentially expressed proteins and 31 downregulated differentially expressed proteins in the RA group. The results indicated that dihydropyrimidinase-related protein 3 (DPYSL3) was significantly upregulated in CD4 + T-cell-derived exosomes, whereas proteasome activator complex subunit 1 (PSME1) was significantly downregulated in the RA group. Bioinformatics analysis showed that proteins were enriched in "positive regulation of gene expression", "antigen processing and presentation", "acute-phase response" and "PI3K-AKT signaling" pathways. ELISA verified that compared to the control group, the RA group showed significant upregulation of DPYSL3, and downregulation of PSME1 in CD4 + T-cell-derived exosomes. CONCLUSIONS: The proteomic analysis results of CD4 + T-cell-derived exosomes from patients with RA suggest that these differentially expressed proteins may be involved in RA pathogenesis. DPYSL3 and PSME1 may become useful biomarkers for RA.
Asunto(s)
Artritis Reumatoide , Exosomas , Humanos , Exosomas/metabolismo , Proteómica , Cromatografía Liquida , Fosfatidilinositol 3-Quinasas/metabolismo , Espectrometría de Masas en Tándem , Linfocitos T CD4-PositivosRESUMEN
Objectives: To compare the proteomics of synovial fluid (SF)-derived exosomes in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), gout, and osteoarthritis (OA) patients. Methods: Exosomes were separated from SF by the Exoquick kit combined ultracentrifugation method. Tandem mass tags (TMT)-labeled liquid chromatography mass spectrometry (LC-MS/MS) technology was used to analyze the proteomics of SF-derived exosomes. Volcano plot, hierarchical cluster, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Results: A total of 1,678 credible proteins were detected. Sixty-nine differentially expressed proteins were found in gout, compared with OA, axSpA, and RA simultaneously. Twenty-five proteins were found highly expressed in gout uniquely, lysozyme C and protein S100-A9 included, whose bioinformatic analysis was significantly involved in "neutrophil degranulation" and "prion diseases". Eighty-four differentially expressed proteins were found in axSpA, compared with OA, gout, and RA simultaneously. Thirty-nine proteins were found highly expressed in axSpA uniquely, RNA-binding protein 8A and protein transport protein Sec24C included, whose bioinformatic analysis was significantly involved in "acute-phase response" and "citrate cycle". One hundred and eighty-four differentially expressed proteins were found in RA, compared with OA, gout, and axSpA simultaneously. Twenty-eight proteins were found highly expressed in RA uniquely, pregnancy zone protein (PZP) and stromelysin-1 included, whose bioinformatic analysis was significantly involved in "serine-type endopeptidase inhibitor activity" and "complement and coagulation cascades". Enzyme-linked immunosorbent assay (ELISA) result showed that the exosome-derived PZP level of SF in RA was higher than that in OA (p < 0.05). Conclusion: Our study for the first time described the protein profiles of SF-derived exosomes in RA, axSpA, gout, and OA patients. Some potential biomarkers and hypothetical molecular mechanisms were proposed, which may provide helpful diagnostic and therapeutic insights for inflammatory arthritis (IA).
Asunto(s)
Artritis Reumatoide , Exosomas , Gota , Osteoartritis , Artritis Reumatoide/metabolismo , Cromatografía Liquida , Exosomas/metabolismo , Gota/metabolismo , Humanos , Osteoartritis/metabolismo , Proteínas/metabolismo , Proteómica , Líquido Sinovial/metabolismo , Espectrometría de Masas en TándemRESUMEN
OBJECTIVES: The study aims to investigate the clinical significance of platelet to albumin ratio (PAR), neutrophil to albumin ratio (NAR), and monocyte to albumin ratio (MAR) in axial spondyloarthritis (axSpA). METHODS: Two hundred and ninety-seven axSpA patients and 71 healthy volunteers were recruited. AxSpA patients were divided into inactive group and active group. Spearman's correlation, receiver operating characteristic (ROC) curves, and binary logistic regression analysis were conducted. RESULTS: Albumin was lower in axSpA group, while neutrophil, platelet, monocyte, NAR, PAR, and MAR were higher (p < .05). Albumin was negatively correlated with BASDAI and BASFI (p < .05). Platelet, NAR, PAR, MAR, ESR, and CRP were all positively correlated with BASDAI and BASFI (p < .05). Albumin was lower in axSpA of active group, while platelet, NAR, PAR, MAR, ESR, and CRP were higher (p < .05). ROC curve indicated that the AUC of PAR for axSpA of active group was higher than that of other variables. The optimal cut-off value of PAR was 6.354, with Youden index of 0.337, specificity of 55.4%, and sensitivity of 78.4%. Logistic regression analysis result suggested that PAR was an independent indicator for axSpA disease activity. CONCLUSIONS: PAR had a high diagnostic value for axSpA of active group. PAR was a novel and reliable indicator for axSpA disease activity.
Asunto(s)
Espondiloartritis Axial , Espondiloartritis , Espondilitis Anquilosante , Albúminas , Plaquetas , Humanos , Curva ROC , Espondiloartritis/diagnóstico , Espondilitis Anquilosante/diagnósticoAsunto(s)
Gota , Hiperuricemia , Enfermedades Renales , Alopurinol/uso terapéutico , Febuxostat/uso terapéutico , Femenino , Gota/tratamiento farmacológico , Supresores de la Gota/uso terapéutico , Humanos , Hiperuricemia/tratamiento farmacológico , Enfermedades Renales/tratamiento farmacológico , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE: This study is aimed at investigating the diagnostic value of synovial fluid cell counts in gout patients. METHODS: A total of 185 gout, 64 rheumatoid arthritis (RA), 26 axial spondyloarthritis (axSpA), and 24 osteoarthritis (OA) patients were included in the study. According to serum uric acid (sUA) levels on attack, gout patients were divided into normal sUA gout patients and high sUA gout patients. The laboratory data were recorded. ROC curves were generated to evaluate the diagnostic value of the variables for gout patients and normal sUA gout patients compared with RA, axSpA, and OA patients. RESULTS: The synovial fluid white blood cell (WBC), peripheral blood mononuclear cell (PBMC), monocyte, polymorphonuclear (PMN), and neutrophil counts in gout patients were higher than those in OA patients (P < 0.05). The synovial fluid PBMC and lymphocyte counts in gout patients were lower than those in RA and axSpA patients (P < 0.05). ROC curve results showed that the AUC values of lymphocytes and sUA for gout patients were 0.728 and 0.881, respectively, which were higher than those of other variables. The optimal cutoff value of lymphocytes for gout was 1.362, with a Youden index of 0.439, a sensitivity of 83.3%, and a specificity of 60.6%. The AUC values of lymphocytes, sUA, and CRP for normal sUA gout patients were 0.694, 0.643, and 0.700, respectively, which were higher than those of other variables. The optimal cutoff value of lymphocytes for normal sUA gout patients was 1.362, with a Youden index of 0.422, a sensitivity of 81.6%, and a specificity of 60.6%. CONCLUSIONS: The synovial fluid cell counts of gout patients were different from those of RA, axSpA, and OA patients. Synovial fluid lymphocytes had a higher diagnostic value for gout.
Asunto(s)
Artritis Reumatoide/patología , Espondiloartritis Axial/patología , Biomarcadores/análisis , Gota/patología , Linfocitos/patología , Osteoartritis/patología , Líquido Sinovial/química , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Estudios RetrospectivosRESUMEN
BACKGROUND: The C-reactive protein (CRP) to albumin (ALB) ratio (CAR) has emerged as a novel inflammatory biomarker. This study was designed to investigate the role of CAR in the disease activity of axial spondyloarthritis (axSpA). METHODS: A total of 241 patients and 61 healthy controls were retrospectively enrolled in this study. AxSpA patients were further divided into the inactive group (n = 176) and active group (n = 65) according to Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) cutoff value of 4. Laboratory data and clinical assessment indices were recorded. Spearman's correlation analysis, receiver operation characteristic (ROC) curve analysis, and binary logistic regression analysis were performed. RESULTS: In axSpA patients, CAR was significantly higher than the healthy group (P < 0.001). Similarly, axSpA patients in the active group had higher CAR than the inactive group (P < 0.001). Besides, CAR was positively correlated with erythrocyte sedimentation rate (ESR) (r = 0.704, P < 0.001), CRP (r = 0.996, P < 0.001), BASDAI (r = 0.329, P < 0.001), and Bath Ankylosing Spondylitis Functional Index (BASFI) (r = 0.330, P < 0.001). ROC curve analysis suggested that the area under the curve (AUC) of CAR for axSpA of the active group was 0.701, which was higher than that of CRP and ESR. The optimal cutoff point of CAR for axSpA of the active group was 0.3644, with a sensitivity and specificity of 58.5% and 79.0%. Binary logistic analysis results revealed that CAR was an independent predictive factor for axSpA disease activity (odds ratio = 4.673, 95% CI: 1.423-15.348, P = 0.011). CONCLUSIONS: CAR was increased in axSpA and axSpA of the active group. CAR may be a novel and reliable indicator for axSpA disease activity.
Asunto(s)
Espondiloartritis Axial/sangre , Espondiloartritis Axial/diagnóstico , Proteína C-Reactiva/metabolismo , Albúmina Sérica/metabolismo , Índice de Severidad de la Enfermedad , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Gout is a common kind of inflammatory arthritis with metabolic disorders. However, the detailed pathogenesis of gout is complex and not fully clear. We investigated the serum metabolic profiling of gout patients by ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). METHODS: Serum metabolites were extracted from 31 gout patients and 31 healthy controls. Metabolite extracts were analyzed in negative mode by UPLC-Q-TOF/MS for global metabolomics. Principal components analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) and hierarchical clustering analysis were performed to detect different compounds between the two groups. Receiver operating characteristic (ROC) curve analysis and pathway analysis of the different metabolites were conducted. RESULTS: A total of 9192 compounds were detected, of which 138 significantly different compounds were selected, according to the criteria of (Variable importance in projection (VIP)â¯>â¯3). Hierarchical clustering analysis showed that the relative levels of the differential compounds were different between the 2 groups. Ninety-one reliable metabolites matching the human metabolome database (HMDB) were confirmed. ROC curve results revealed that 4-hydroxytriazolam, urate and bilirubin exerted higher AUC values. Pathway analysis indicated that the significantly different metabolites were mainly involved in primary bile acid biosynthesis, purine metabolism and glycerophospholipid metabolism. CONCLUSIONS: The serum metabolic profiling of gout patients was significantly different from healthy subjects based on UPLC-Q-TOF/MS. Bilirubin was the potential biomarker. Primary bile acid biosynthesis may be a novel metabolic pathway of gout.
Asunto(s)
Gota , Metabolómica , Biomarcadores , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Humanos , Espectrometría de Masas , MetabolomaRESUMEN
BACKGROUND: Gout is an inflammatory disease characterized by the deposition of monosodium urate (MSU) in synovial fluid and other tissues. Many studies have shown that the activation of coagulation system had been proposed correlated with systemic inflammation. The concentrations of plasma fibrinogen and D-dimer are increased in abnormal coagulation, emerging as available indicators to predict systemic inflammation. The aim of this study is to reveal the predictive value of plasma fibrinogen, D-dimer in the disease activity of gout patients. METHODS: This retrospective study included 334 gout patients and 101 age- and gender- matched healthy controls. The gout patients were divided into two groups according to the gout activity score (GAS = 0.09 × last 12 month attacks + 1.01 × sUA + 0.34 × VAS patient + 0.53 × ln(1 + tophi number). The remission group included 46 patients with GAS of lower than 2.5 and the active group included 288 patients with GAS of 2.5 or higher. Clinical and laboratory data were recorded. The correlations between plasma fibrinogen, D-dimer and GAS were analyzed by Spearman's correlation analysis and Partial correlation analysis. Receiver operating characteristic (ROC) was used to evaluate the diagnostic value for the active group compared with remission group. The predictive value of fibrinogen, D-dimer to the disease activity of gout patients was tested by Binary logistic regression analysis. RESULTS: Plasma fibrinogen and D-dimer in gout patients (3.66 (2.88, 5.20), 0.29 (0.22, 0.80)) were increased as compared with the control group (2.88 (2.51, 3.24), 0.22 (0.22, 0.32), both P < 0.001). Fibrinogen and D-dimer in active group (3.91 (3.00, 5.53), 0.34 (0.22, 0.86)) were higher than those in remission group (2.88 (2.34, 3.22), 0.22 (0.22, 0.26), both P < 0.001)). Plasma fibrinogen, D-dimer, ESR and CRP were positively correlated with GAS (r = 0.606, r = 0.419, r = 0.570, r = 0.440, all P < 0.001). ROC curve showed fibrinogen yielded a highest AUC than D-dimer, ESR, CRP. In addition, the optimal cutoff value of fibrinogen for active group was 3.60, with a specificity of 89.1% and sensitivity of 58.3%. Binary logistic regression analysis showed fibrinogen (odds ratio = 2.71, 95% confidence interval: 1.28-5.74, p = 0.011) was a predictor for gout disease activity. CONCLUSION: Fibrinogen was increased in active gout group. Fibrinogen can serve as a reliable inflammatory marker for monitoring inflammatory response and disease activity in gout patients.
Asunto(s)
Fibrinógeno , Gota , Biomarcadores , Productos de Degradación de Fibrina-Fibrinógeno , Fibrinógeno/análisis , Gota/diagnóstico , Humanos , Curva ROC , Estudios RetrospectivosRESUMEN
BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease, whose pathogenesis is still unclear. Many studies show the proteins in extracellular vesicle (EVs) would change regularly in many diseases. The study aims to explore the proteins contents of serum-derived EVs in AS patients. METHODS: EVs were separated by ExoQuickTM kit. The protein profiles of AS patients and healthy subjects were analyzed by Label-free-liquid chromatography mass spectrometry (LC-MS/MS) technology. Enzyme-linked immunosorbent assay (ELISA) was used to verify the levels of the differently expressed proteins. Receiver operation characteristic (ROC) curves and bioinformatic analysis were conducted. RESULTS: Six hundred and ten serum-derived EVs proteins from AS patients were detected. Seventy-three diferentially expressed proteins were found in AS group, compared with healthy subjects. Of these, 31 proteins were up-regulated in AS group, while 42 proteins were down-regulated. ELISA result showed that EVs-derived serum amyloid A-1 (SAA1) was higher in AS group, which was consistent with the Label-free-LC-MS/MS data. ROC curves result revealed that the area under curve (AUC) value of EVs-derived SAA1 for AS was 0.768 (0.652-0.885). Bioinformatic analysis revealed that the differently expressed proteins in AS group were significantly involved in "complement and coagulation cascades", "staphylococcus aureus infection", "systemic lupus erythematosus" and "PI3K-Akt signaling pathway". CONCLUSIONS: The protein profiles of serum-derived EVs in AS patients and healthy subjects were different. EVs-derived SAA1 may be a potential biomarkes of AS. The function analysis indicated that the differentially expressed proteins may potentially participate in immune response.
Asunto(s)
Proteínas Sanguíneas/metabolismo , Vesículas Extracelulares , Espondilitis Anquilosante/metabolismo , Adulto , Femenino , Humanos , Masculino , Proteómica , Espondilitis Anquilosante/genética , Adulto JovenRESUMEN
Aicardi-Goutières syndrome (AGS) is characterized by progressive neurologic decline, cerebral calcification, and variable manifestations of autoimmunity. Seven subtypes of AGS have been defined and aberrant activation of the type I interferon system is a common theme among these conditions. We describe a 13-year-old boy who presented with an unusual constellation of psoriasis, interstitial lung disease (ILD), and pulmonary hypertension in addition to cerebral calcifications and glomerulonephritis. He was found to have late-onset AGS due to a gain-of-function mutation in IFIH1 and over-activation of the type I interferon pathway was confirmed by RNA sequencing. The majority of his clinical manifestations, including ILD, psoriasis and renal disease improved markedly after treatment with the combination of corticosteroids, cyclophosphamide, and the Janus-kinase inhibitor tofacitinib. This case extends the clinical spectrum of AGS and suggests the need for lung disease screening in patients with AGS.
Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso/complicaciones , Enfermedades Pulmonares Intersticiales/etiología , Malformaciones del Sistema Nervioso/complicaciones , Psoriasis/etiología , Adolescente , Corticoesteroides/uso terapéutico , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/tratamiento farmacológico , Enfermedades Autoinmunes del Sistema Nervioso/genética , Mutación con Ganancia de Función , Predisposición Genética a la Enfermedad , Humanos , Inmunosupresores/uso terapéutico , Helicasa Inducida por Interferón IFIH1/genética , Inhibidores de las Cinasas Janus/uso terapéutico , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Masculino , Malformaciones del Sistema Nervioso/diagnóstico , Malformaciones del Sistema Nervioso/tratamiento farmacológico , Malformaciones del Sistema Nervioso/genética , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: This study aimed to assess the role of fibrinogen (Fib) to albumin (ALB) ratio (FAR) in ankylosing spondylitis (AS) and its association with disease activity. METHODS: 135 AS patients and 76 age - and gender - matched healthy controls were collected in this retrospective study. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was used to divide the AS patients into remission group (BASDAI < 4) and active group (BASDAI ≥ 4). The association between FAR and BASDAI was evaluated by Spearman correlation. Receiver operating characteristic (ROC) curve was made to determine the area under curve (AUC) value. The prognostic value of FAR in the AS disease activity was tested by multivariate logistical regression analyses. RESULTS: AS patients showed higher FAR levels than the controls (P < 0.001). FAR was also increased in active group of AS patients than those in inactive group (P < 0.001). Spearman analyses showed that FAR was positively related with BASDAI (r = 0.594, P < 0.001) in AS patients. ROC curve analyses revealed that the AUC of FAR was higher than ALB and Fib. In addition, the optimal cutoff value of FAR for AS diagnosis was 78.84, with a specificity of 88.2% and sensitivity of 77.0%. Logistical regression analyses showed that FAR (odds ratio = 13.091, 95% confidence interval: 4.686-36.571, P < 0.001) was a predictor for AS disease activity. CONCLUSIONS: FAR was increased in AS and may act as a novel inflammatory parameter for mirroring disease activity in AS.
Asunto(s)
Albúminas/análisis , Fibrinógeno/análisis , Espondilitis Anquilosante/sangre , Adulto , Área Bajo la Curva , Biomarcadores/sangre , Femenino , Humanos , Recuento de Linfocitos , Masculino , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Valores de Referencia , Estudios RetrospectivosRESUMEN
Background: Interleukin (IL)-18 is a pro-inflammatory cytokine that has important functions in host defense. The maturation and secretion of IL-18 has been shown to be regulated by the NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome. Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), in association with lipopolysaccharide (LPS), is able to promote the secretion of IL-18, but the mechanism remains unknown. This study aims to explore the mechanism by which MPA synergizes with LPS to induced IL-18 release. Methods: THP-1 cells were stimulated with LPS and MPA and treated with or without the inhibitors of caspase-1, Ac-YVAD-cmk or KCl; IL-18 in the supernatants was measured by ELISA. The intracellular protein levels of NF-κB p-p65, pro-IL-18, NLRP3, and cleaved caspase-1(p20) were measured by Western blot. Results: We found that MPA alone failed to induce IL-18, whereas MPA enhanced LPS-mediated IL-18 release. MPA did not affect the intracellular protein levels of NF-κB p-p65 or pro-IL-18 but activated the NLRP3 inflammasome. Ac-YVAD-cmk or increasing extracellular K+ blocked the activation of caspase-1 and attenuated the release of IL-18. Conclusions: Taken together, MPA synergized with LPS to induce the release of IL-18 via activating the NLRP3 inflammasome and increasing the degradation of pro-IL-18, rather than by enhancing the production of pro-IL-18.
Asunto(s)
Inflamasomas/metabolismo , Interleucina-18/metabolismo , Lipopolisacáridos/farmacología , Ácido Micofenólico/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sinergismo Farmacológico , Humanos , Lipopolisacáridos/administración & dosificación , Ácido Micofenólico/administración & dosificación , Células THP-1RESUMEN
OBJECTIVES: To describe clinical characteristics of ulceration over tophi in patients with gout and determine risk factors associated with ulceration. METHODS: Patients presenting with tophi or ulceration(s) over tophi were prospectively recruited and their clinical characteristics were recorded. Comparison of clinical characteristics and risk factors for ulceration were analyzed between groups. RESULTS: A total of 105 patients were enrolled. Thirty-three patients with ulcerations were older, with prolonged duration with gout and tophi, a higher rate of obesity, greater numbers of tophi, lower levels of glomerular filtration rate (GFR), and higher levels of serum creatinine, erythrocyte sedimentation rate and C-reactive protein. The mean duration of ulceration was 1.63 ± 2.32 months. The ulcerations were mainly located in the ankle (34.21%) and metatarsophalangeal joints (39.47%), with a mean size of 32.37 × 22.76 mm. The majority of ulcerations were categorized as stage I (42.4%) and stage II (51.5%). In univariate regression analysis, age, glucocorticoid overuse, gout duration, tophi duration, tophi number and GFR were associated with ulceration. In the multivariable model, significant differences were demonstrated in glucocorticoid overuse, tophi duration, tophi number. CONCLUSIONS: Gout patients with ulceration(s) over tophi present several different aspects of clinical characteristics compared with those without ulceration. The ulcerations are most commonly seen in feet and they are mainly categorized as stages I and II. Glucocorticoid overuse, prolonged duration with tophi and greater numbers of tophi are risk factors for ulceration over tophi.
Asunto(s)
Articulación del Tobillo/patología , Gota/complicaciones , Articulación Metatarsofalángica/patología , Úlcera Cutánea/etiología , Piel/patología , Adulto , Anciano , Femenino , Gota/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Úlcera Cutánea/patologíaRESUMEN
Purpose: We assessed the prevalence of metabolic syndrome (MetS) and associated factors in mainland Chinese patients with ankylosing spondylitis (AS). Patients and methods: A retrospective study was conducted in 117 AS patients and 117 age- and sex-matched healthy controls. Parameters of MetS based on the criteria established by the Chinese Diabetes Society in 2013 were tabulated. Demographic features, laboratory data, and clinical characteristics were also collected. Independent factors correlated with MetS in AS patients were identified by backward stepwise multivariate analysis. Results: The prevalence of MetS was higher in AS patients than in healthy controls (P= 0.026). AS patients also had higher blood pressure and fasting serum glucose levels, but generally lower serum lipid levels. AS patients with and without MetS had no distinct differences in disease duration, medication usage, disease activity, or biomarkers of inflammation. Multivariable logistic regression analysis showed that hyperuricemia (odds ratio [OR] = 2.385, 95% confidence interval [95% CI] = 1.019-5.582, P= 0.045) and high body mass index (BMI, OR = 5.165; 95% CI = 1.935-13.787, P=0.001) were independent factors for MetS in AS patients. Conclusion: Chinese AS patients living in the mainland have an increased risk of developing MetS. Hyperuricemia and high BMI are predictors of MetS in AS patients.
RESUMEN
BACKGROUND: Axial spondyloarthritis (axSpA) is a progressive, chronic, inflammatory skeletal disorder affecting the spine and sacroiliac joints. Many studies have shown that neutrophils, lymphocytes, monocytes, platelets, and red blood cells (RBCs) play important roles in the inflammatory process of axSpA. Neutrophils to lymphocytes ratio (NLR) and red blood cell distribution width (RDW) have been reported to be simple and inexpensive markers to indicate the disease activity of axSpA. However, the role of monocytes to lymphocytes ratio (MLR) and platelets to lymphocytes ratio (PLR) in axSpA was rarely mentioned. OBJECTIVE: The study's aim was to determine the role of MLR and PLR in axSpA patients and to investigate their relationships with disease severity. METHODS: AxSpA patients who fulfilled the Assessment in Ankylosing Spondylitis International Society classification criteria published in 2009 were enrolled in this study and divided into nonradiographic axial spondyloarthritis (nr-axSpA) group and ankylosing spondylitis (AS) group. Healthy age and gender-matched subjects were also enrolled as control group. MLR, PLR, NLR, RDW, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) level were assessed. The correlation between the variables with finger-to-floor distance, Modified Schober test, and occiput-to-wall distance were tested with Pearson correlation. Furthermore, area under curve (AUC) value, sensitivity, specificity, and the optimal cutoff values were determined using receiver operating characteristic (ROC) curves. RESULTS: A total of 148 axSpA patients (67 nr-axSpA patients and 81 AS patients) and 58 healthy subjects were included in the study. The MLR, NLR, PLR, and RDW in axSpA group were higher than those in the control group (Pâ¯<â¯0.05). Among them, MLR and RDW were highly increased in AS group compared with the nr-axSpA group (Pâ¯<â¯0.05). MLR, NLR, PLR, and RDW were all positively correlated with ESR level and CRP level (Pâ¯<â¯0.05). MLR and RDW were positively correlated with finger-to-floor distance and negatively correlated with Modified Schober test (Pâ¯<â¯0.05). RDW was positively correlated with occiput-to-wall distance (Pâ¯<â¯0.05). ROC curve results showed MLR yielded a higher AUC than NLR, PLR, and RDW (Pâ¯<â¯0.05). In addition, the optimal cutoff value of MLR for axSpA was 0.22, with a specificity of 70.9% and sensitivity of 68.4%. CONCLUSIONS: MLR was elevated in AS patients compared to nr-axSpA patients and had a close relationship with CRP level, ESR level, and spine movements. MLR may be a reliable, cost-effective, and novel potential parameter to evaluate disease severity in axSpA.