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OBJECTIVE: This study aimed to identify variables that predict gout remission in people with erosive gout receiving urate-lowering therapy. METHODS: We analysed data from a 2-year, double-blind randomized-controlled trial of people with erosive gout, randomized to a serum urate target of <0.20mmol/l or <0.30mmol/l using oral urate-lowering therapies. All participants had dual energy CT (DECT) scans of the feet and ankles at baseline. The proportion of participants achieving gout remission according to the 2016 preliminary gout remission criteria and simplified gout remission criteria (without the patient reported outcomes) was analyzed. Logistic regression models were used to evaluate predictors of gout remission in Year 2. RESULTS: The preliminary gout remission criteria were fulfilled in 11/97 (11%) participants at Year 1 and 21/92 (23%) participants at Year 2. The simplified criteria were fulfilled in 26/97 (27%) participants in Year 1 and 40/92 (44%) participants in Year 2. In multivariable regression models, baseline DECT monosodium urate crystal volume was the only significant independent predictor of gout remission at Year 2, using either criteria. Each one cm3 increase in the baseline DECT monosodium urate crystal volume decreased the odds of fulfilling the 2016 preliminary gout remission criteria (0.65 [95% CI 0.46-0.93], p=0.02), and the simplified gout remission criteria (0.57 [95% CI 0.41-0.78], p<0.001). CONCLUSIONS: In people with erosive gout on urate-lowering therapy, higher baseline DECT monosodium urate crystal volume is associated with lower odds of gout remission after two years of treatment, defined by either the preliminary gout remission criteria or simplified gout remission criteria.
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Background/Aims: The Gout Impact Scale (GIS), a part of the Gout Assessment Questionnaire 2.0, is used to measure gout-specific health-related quality of life (HRQOL). Although several studies have been conducted on the factors affecting the HRQOL of patients with gout, few have focused on lifestyle factors. This study aimed to investigate the correlation between lifestyle habits and HRQOL using the GIS in patients with gout. Methods: We used data from the Urate-Lowering TheRApy in Gout (ULTRA) registry, a prospective cohort of Korean patients with gout treated at multiple centers nationwide. The patients were aged ≥18 years and met the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria. They were asked to complete a GIS and questions regarding their lifestyle habits at enrollment. Results: The study included 232 patients. 'Gout concern overall' scores in the GIS were significantly lower in patients who exercised more frequently and consumed soft drinks and meat less, and 'well-being during attack' scores were significantly lower in patients who consumed vegetables and exercised more frequently. The frequency of vegetable consumption had a negative linear relationship with the 'well-being during attack' and 'gout concern during attack' scores (p = 0.01, p = 0.001, respectively). The frequency of exercise had a negative linear relationship with the 'gout concern overall' and 'gout concern during attack' scores (p = 0.04 and p = 0.002, respectively). Conclusions: Patients with gout who frequently consumed vegetables and exercised regularly experienced less impact of gout, exhibiting a better GIS that represented HRQOL.
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Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder characterized by joint destruction due to synovial hypertrophy and the infiltration of inflammatory cells. Despite substantial progress in RA treatment, challenges persist, including suboptimal treatment responses and adverse effects associated with current therapies. This study investigates the anti-rheumatic capabilities of the newly identified multi-protein kinase inhibitor, KMU-11342, aiming to develop innovative agents targeting RA. In this study, we synthesized the novel multi-protein kinase inhibitor KMU-11342, based on indolin-2-one. We assessed its cardiac electrophysiological safety using the Langendorff system in rat hearts and evaluated its toxicity in zebrafish in vivo. Additionally, we examined the anti-rheumatic effects of KMU-11342 on human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), THP-1 cells, and osteoclastogenesis in RAW264.7 cells. KMU-11342 demonstrated the ability to inhibit LPS-induced chemokine inhibition and the upregulation of pro-inflammatory cytokines, cyclooxygenase-2, inducible nitric oxide synthase, p-IKKα/ß, p-NF-κB p65, and the nuclear translocation of NF-κB p65 in RA-FLS. It effectively suppressed the upregulation of NLR family pyrin domain containing 3 (NLRP3) and caspase-1 cleavage. Furthermore, KMU-11342 hindered the activation of osteoclast differentiation factors such as RANKL-induced TRAP, cathepsin K, NFATc-1, and c-Fos in RAW264.7 cells. KMU-11342 mitigates LPS-mediated inflammatory responses in THP-1 cells by inhibiting the activation of NLRP3 inflammasome. Notably, KMU-11342 exhibited minimal cytotoxicity in vivo and electrophysiological cardiotoxicity ex vivo. Consequently, KMU-11342 holds promise for development as a therapeutic agent in RA treatment.
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Antirreumáticos , Artrite Reumatoide , Sinoviócitos , Peixe-Zebra , Animais , Humanos , Camundongos , Artrite Reumatoide/tratamento farmacológico , Células RAW 264.7 , Sinoviócitos/efeitos dos fármacos , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Ratos , Masculino , Citocinas/metabolismo , Células THP-1 , Indóis/farmacologia , Indóis/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Ratos Sprague-DawleyRESUMO
Objective: We compared the osteoblastogenesis by serially administrating recombinant human bone morphogenetic protein-2 (rhBMP-2) and osteoprotegerin-immunoglobulin Fc segment complex (OPG-Fc). Methods: The MC3T3-E1 preosteoblast cell line was differentiated for 1, 3, and 7 days with a treatment of OPG-Fc in 10~200 ng/mL concentration and the cell viability was evaluated by Cell Counting Kit-8 analysis. The level of differentiation from MC3T3-E1 cells to osteoblasts was determined by alkaline phosphatase activity. The level of runt domain-containing transcription factor 2 (Runx2) and osteopontin (OPN) manifestation, involved in osteoblast differentiation, was examined by real-time polymerase chain reaction and western blotting. Results: During MC3T3-E1 cell differentiation, the differentiation level was high with 1-day treatment using 100 ng/mL OPG-Fc. The treatment with 50 ng/mL rhBMP-2 for 7 days, followed by 1-day treatment with 100 ng/mL OPG-Fc produced the highest differentiation level, which was approximately 5.3 times that of the control group (p<0.05). The expression of Runx2 mRNA significantly increased, reaching 2.5 times the level of the control group under the condition of 7-day treatment with rhBMP-2 and 1-day treatment with OPG-Fc (p<0.001). The expression of Runx2 protein significantly increased to approximately 5.7 times that of the control group under the condition of 7-day treatment with rhBMP-2, followed by 1-day treatment with OPG-Fc (p<0.01). The expression of OPN protein showed no change from that of the control group under various conditions of rhBMP-2 and OPG-Fc combinations. Conclusion: These results imply that the treating preosteoblasts with rhBMP-2 first and then with OPG-Fc increased osteoblast differentiation efficacy.
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Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by excessive new bone formation. We previously reported that the complement factor H-related protein-5 (CFHR5), a member of the human factor H protein family, is significantly elevated in patients with AS compared to other rheumatic diseases. However, the pathophysiological mechanism underlying new bone formation by CFHR5 is not fully understood. In this study, we revealed that CFHR5 and proinflammatory cytokines (TNF, IL-6, IL-17A, and IL-23) were elevated in the AS group compared to the HC group. Correlation analysis revealed that CFHR5 levels were not significantly associated with proinflammatory cytokines, while CFHR5 levels in AS were only positively correlated with the high CRP group. Notably, treatment with soluble CFHR5 has no effect on clinical arthritis scores and thickness at hind paw in curdlan-injected SKG, but significantly increased the ectopic bone formation at the calcaneus and tibia bones of the ankle as revealed by micro-CT image and quantification. Basal CFHR5 expression was upregulated in AS-osteoprogenitors compared to control cells. Also, treatment with CFHR5 remarkedly induced bone mineralization status of AS-osteoprogenitors during osteogenic differentiation accompanied by MMP13 expression. We provide the first evidence demonstrating that CFHR5 can exacerbate the pathological bone formation of AS. Therapeutic modulation of CFHR5 could be promising for future treatment of AS. KEY MESSAGES: Serum level of CFHR5 is elevated and positively correlated with high CRP group of AS patients. Recombinant CFHR5 protein contributes to pathological bone formation in in vivo model of AS. CFHR5 is highly expressed in AS-osteoprogenitors compared to disease control. Recombinant CFHR5 protein increased bone mineralization accompanied by MMP13 in vitro model of AS.
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Espondilite Anquilosante , Humanos , Fator H do Complemento/uso terapêutico , Proteínas do Sistema Complemento/metabolismo , Citocinas , Metaloproteinase 13 da Matriz , Osteogênese , Espondilite Anquilosante/patologiaRESUMO
BACKGROUND: Dual energy computed tomography (DECT) allows direct visualization of monosodium urate crystal deposition in gout. However, DECT urate volume data are often highly skewed (mostly small volumes with the remainder considerably larger), making statistical analyses challenging in longitudinal research. The aim of this study was to explore the ability of various analysis methods to normalise DECT urate volume data and determine change in DECT urate volumes over time. METHODS: Simulated datasets containing baseline and year 1 DECT urate volumes for 100 people with gout were created from two randomised controlled trials. Five methods were used to transform the DECT urate volume data prior to analysis: log-transformation, Box-Cox transformation, log(X-(min(X)-1)) transformation; inverse hyperbolic sine transformation, and rank order. Linear regression analyses were undertaken to determine the change in DECT urate volume between baseline and year 1. Cohen's d were calculated as a measure of effect size for each data treatment method. These analyses were then tested in a validation clinical trial dataset containing baseline and year 1 DECT urate volumes from 91 people with gout. RESULTS: No data treatment method successfully normalised the distribution of DECT urate volumes. For both simulated and validation data sets, significant reductions in DECT urate volumes were observed between baseline and Year 1 across all data treatment methods and there were no significant differences in Cohen's d effect sizes. CONCLUSIONS: Normalising highly skewed DECT urate volume data is challenging. Adopting commonly used transformation techniques may not significantly improve the ability to determine differences in measures of central tendency when comparing the change in DECT urate volumes over time.
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Gota , Ácido Úrico , Humanos , Tomografia Computadorizada por Raios X/métodos , Gota/diagnóstico por imagem , Gota/tratamento farmacológico , Supressores da Gota/uso terapêuticoRESUMO
Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.
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Gota , Ácido Úrico , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Supressores da Gota/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Análise MultivariadaRESUMO
OBJECTIVE: The efficacy and safety of febuxostat in patients with stage 4-5 chronic kidney disease (CKD) remains unclear. We evaluated the urate-lowering efficacy and renal safety of febuxostat in patients with stage 4-5 CKD not yet on dialysis, through a meta-analysis of observational studies. METHODS: We performed a systematic search in PubMed, Ovid MEDLINE, Embase, and the Cochrane Library databases for observational studies of patients with advanced CKD starting febuxostat. Articles describing changes in serum urate levels and/or renal function assessed by the estimated glomerular filtration rate (eGFR) were included. RESULTS: Among 148 retrieved studies, five relevant observational studies with 327 patients were included in the meta-analysis. Febuxostat was administered daily at 10-120 mg for 3-12 months. Serum urate reduced in response to febuxostat (weighted mean difference, -1.85 mg/dL; 95% CI, -2.04--1.67 mg/dL; I2; 0%). Three studies involving 145 patients included eGFR assessments. Renal function, assessed through the eGFR, did not change after febuxostat use (weighted mean difference, 0.11 mL/min/1.73m2; 95% CI, -0.25-0.47 mL/min/1.73m2; I2; 45%). CONCLUSION: Overall, febuxostat has acceptable urate-lowering efficacy and renal safety in patients with hyperuricemia and stage 4-5 CKD who are not yet on dialysis.
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Hiperuricemia , Falência Renal Crônica , Insuficiência Renal Crônica , Alopurinol/uso terapêutico , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/complicações , Hiperuricemia/tratamento farmacológico , Rim/fisiologia , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Resultado do Tratamento , Ácido ÚricoRESUMO
Objectives: In this study, we aimed to evaluate the association between grape seed proanthocyanidin extract (GSPE) and rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) and to investigate whether GSPE induces cell death in RA-FLSs. Materials and methods: The FLSs were isolated from RA synovial tissues. Cell viability and cell cycle staging were analyzed using a hemocytometer and flow cytometry. Caspase 3 and poly (ADP-ribose) polymerase (PARP) proteins were analyzed using Western blotting with z-VAD-fmk. Protein LC3 and polyubiquitin-binding protein p62 that were degraded by autophagy were evaluated using Western blotting with 3-methyladenine and chloroquine. Reactive oxygen species (ROS) were also evaluated. Results: When RA-FLSs were treated with GSPE, cell viability decreased, the number of cells in sub-G1 and G2/M phases increased, and the expression of pro-PARP and pro-caspase 3 proteins decreased in a concentration-dependent manner. This result was offset, when the cells were co-treated with the pan-caspase inhibitor z-VAD-fmk. The reduced cell viability, increased expression of LC3-II protein, and reduced expression of p62 protein with GSPE treatment were offset, when RA-FLSs were co-treated with GSPE and autophagy inhibitors 3-methyladenine and chloroquine. The level of ROS in RA-FLSs treated with GSPE was significantly lower than treatment with N-acetyl-cysteine, a ROS inhibitor. Conclusion: Our study results show that GSPE induces apoptotic and autophagic cell death and inhibites reactive oxygen species in RA-FLSs.
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BACKGROUND: Features of new bone formation (NBF) are common in tophaceous gout. The aim of this project was to develop a plain radiographic scoring system for NBF in gout. METHODS: Informed by a literature review, scoring systems were tested in 80 individual 1st and 5th metatarsophalangeal joints. Plain radiography scores were compared with computed tomography (CT) measurements of the same joints. The best-performing scoring system was then tested in paired sets of hand and foot radiographs obtained over 2 years from an additional 25 patients. Inter-reader reproducibility was assessed using intraclass correlation coefficients (ICC). NBF scores were correlated with plain radiographic erosion scores (using the gout-modified Sharp-van der Heijde system). RESULTS: Following a series of structured reviews of plain radiographs and scoring exercises, a semi-quantitative scoring system for sclerosis and spur was developed. In the individual joint analysis, the inter-observer ICC (95% CI) was 0.84 (0.76-0.89) for sclerosis and 0.81 (0.72-0.87) for spur. Plain radiographic sclerosis and spur scores correlated with CT measurements (r = 0.65-0.74, P < 0.001 for all analyses). For the hand and foot radiograph sets, the inter-observer ICC (95% CI) was 0.94 (0.90-0.98) for sclerosis score and 0.76 (0.65-0.84) for spur score. Sclerosis and spur scores correlated highly with plain radiographic erosion scores (r = 0.87 and 0.71 respectively), but not with change in erosion scores over 2 years (r = -0.04-0.15). CONCLUSION: A semi-quantitative plain radiographic scoring method for the assessment of NBF in gout is feasible, valid, and reproducible. This method may facilitate consistent measurement of NBF in gout.
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Gota , Osteogênese , Gota/diagnóstico por imagem , Mãos , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
AIM: The incorporation of growth factors is an effective strategy to accelerate bone induction. Bone morphogenetic protein-2 (BMP-2) promotes osteoblast differentiation and induces bone formation. Alendronate (ALN) is an osteoclast deactivation drug. We investigated the effect of serial administration of recombinant human BMP-2 (rhBMP-2) and ALN on osteoblast differentiation. METHODS: The effect of serial administration of rhBMP-2 (0-150 ng/mL) and ALN (0-15 µmol/L) on the viability and differentiation of a clonal murine calvarial cell line, MC3T3-E1, was evaluated at various concentrations and for different periods. The Cell Counting Kit-8 assay was used to assess cell viability. The alkaline phosphatase activity was evaluated as an indicator of osteogenic differentiation. The expression levels of runt domain-containing transcription factor 2 (Runx2) and osteopontin (OPN) were analyzed by real-time polymerase chain reaction and western blotting. Statistical analyses were performed using Student's t test. RESULTS: The serial treatment with rhBMP-2 and ALN increased the expression of the differentiation-related factors Runx2 and OPN, as well as the differentiation ability of osteoblasts compared with individual or simultaneous treatment. The osteoblasts treated with rhBMP-2 followed by ALN showed the highest differentiation. The degree of differentiation in the group treated with rhBMP-2 for 7 days followed by ALN for 3 days was increased by 1.5 times compared with that of the group treated with rhBMP-2 alone (P < .01). CONCLUSION: These findings indicate that the serial administration of rhBMP-2 and ALN may exert osteogenic effects on osteoblastic cells via the upregulation of Runx2 and OPN.
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Alendronato/farmacologia , Conservadores da Densidade Óssea/farmacologia , Proteína Morfogenética Óssea 2/farmacologia , Diferenciação Celular/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Células 3T3 , Fosfatase Alcalina/metabolismo , Animais , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Camundongos , Osteoblastos/metabolismo , Osteopontina/genética , Osteopontina/metabolismo , Proteínas Recombinantes/farmacologiaRESUMO
BACKGROUND: International rheumatology guidelines advocate a treat to serum urate target (T2T) approach for gout management. While individual studies have reported regional and national-level gout management, global patterns in gout care have not been synthesized. This study aimed to systematically review and meta-analyze global T2T care for patients with gout. METHODS: Electronic databases were searched for studies reporting medication and serum urate testing in patients with gout. Meta-analyses were conducted to determine the pooled proportion of patients with gout achieving pre-specified T2T indicators. RESULTS: Sixty-seven papers were included from North America (n = 31 studies), Europe (n = 22), Oceania (n = 7), Asia (n = 6), and reporting data from multiple continents (n = 1). The global pooled percentages (95% confidence interval (CI)) of patients with gout achieving T2T indicators were: 52% (45%, 59%) on urate lowering therapy (ULT), 50% (40%, 61%) on ULT receiving regular uninterrupted ULT, 53% (40%, 65%) on ULT having any serum urate testing, and 34% (28%, 41%) on ULT achieving a serum urate target. CONCLUSION: Outside North America and Europe, there are relatively few studies about T2T care for gout management. However, available data demonstrate that a minority of people with gout receive T2T care worldwide. For those prescribed ULT, there are low rates of continuous therapy, serum urate testing, and achievement of serum urate target.
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Gota , Reumatologia , Gota/tratamento farmacológico , Supressores da Gota/uso terapêutico , Humanos , Projetos de Pesquisa , Ácido ÚricoAssuntos
Escleroderma Sistêmico , Úlcera Cutânea , Bosentana , Dedos , Humanos , República da Coreia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/etiologia , ÚlceraRESUMO
Objective: High disease activity of ankylosing spondylitis (AS) is associated with poor sleep quality The purpose of this study was to identify which of the representative tools for evaluating the disease activity of AS best reflect the quality of sleep. Methods: A total of 107 AS patients were enrolled in the study and the sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) Age, sex, concomitant medication, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, Beck Depression Inventory second edition (BDI-II), Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS)-ESR, ASDAS-CRP, pain visual analog scale, Insomnia Severity Index (ISI), and Epworth Sleepiness Scale (ESS) were analyzed as covariates. Results: Overall, 65% (70/107) of subjects reported poor sleep quality (PSQI>5) There was a positive correlation between the sleep quality and disease activity as measured by the BASDAI, ASDAS-ESR, and ASDAS-CRP In addition, the BASDAI demonstrated good correlations with ISI, ESS, and BDI-II, respectively However, only BASDAI showed reliable correlation with PSQI among the disease activity parameters of AS (adjusted odd ratio 5.36, p=0.023). Conclusion: BASDAI is the most reliable parameter of disease activity associated with the sleep quality in patients with AS.
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Objective: Both hypouricemia and hyperuricemia are reportedly associated with reduced kidney function This study investigated the association between uric acid levels and the risk of reduced renal function in men and women. Methods: We conducted a cross-sectional study using data from a government-funded health examinee cohort of a Korean genome and epidemiological study A total of 172,970 participants (58,981 men, 113,989 women) aged 40â¼79 years were included A logistic regression test was performed, and the odds ratio (OR) and 95% confidence interval (CI) were calculated to examine the relationship between stratified uric acid levels and the frequency of chronic kidney disease. Results: As the uric acid level increased, the risk of reduced renal function increased Moreover, for uric acid levels ≤20 mg/dL, the risk of reduced renal function was higher than that of the reference group Among the total, man, and woman groups, a statistically significant association was observed in men (OR 171, 95% CI 0945â¼3111, OR 5003, 95% CI 1405â¼17809, and OR 1377, 95% CI 0696â¼2724, respectively). Conclusion: The OR of reduced renal function according to uric acid levels formed a J-shaped curve in both genders.
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BACKGROUND/AIMS: We investigated the distribution of serum uric acid (SUA) levels and estimated the prevalence of hyperuricemia and hypouricemia in the Korean population. METHODS: This cross-sectional study used data from the Korean Genome and Epidemiology Study and included 172,970 participants (58,981 men and 113,989 women) aged 40 to 79 years. Hypouricemia and hyperuricemia were defined as SUA level ≤ 2.0 mg/dL and > 7 mg/dL, respectively. The prevalence of hyperuricemia and hypouricemia was evaluated by age and sex. RESULTS: The mean SUA levels were significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001). The mean SUA levels and prevalence of hyperuricemia increased with age in women but not in men. The overall prevalence of hyperuricemia and that in men and women was 50.82, 133.25, and 8.17 per 1,000 persons, respectively; the overall prevalence of hypouricemia and that in men and women was 4.16, 1.10, and 5.75 per 1,000 persons, respectively. The prevalence of hypouricemia in men was similar across all age groups; however, that in women was the highest in the age group of 40 to 49 years and the lowest in the age group of 50 to 59 years. CONCLUSION: The distribution of SUA levels and prevalence of hyperuricemia and hypouricemia differed according to age and sex. Age and sex should be considered in studies on uric acid-related diseases.
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Hiperuricemia , Ácido Úrico , Adulto , Estudos Transversais , Feminino , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease affecting the axial skeleton and peripheral joints. The etiology of this disease remains poorly understood, but interactions between genetic and environmental factors have been implicated. The present study identified differentially expressed proteins in the synovial fluid (SF) of AS patients to elucidate the underlying cause of AS. METHODS: A cohort of 40 SF samples from 10 AS and 10 each of rheumatoid arthritis (RA), gout, and osteoarthritis (OA) patients were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins specific to AS. The label-free LC-MS/MS results were verified by western blotting. RESULTS: We identified 8 proteins that were > 1.5-fold upregulated in the SF of AS patients compared to that of the disease control groups, including HP, MMP1, MMP3, serum amyloid P-component (APCS), complement factor H-related protein 5 (CFHR5), mannose-binding lectin 2 (MBL2), complement component C9 (C9), and complement C4-A (C4A). CFHR5 and C9 were previously found in serum from AS patients, while APCS was previously found in SF as well as in serum. However, the present study has identified C4A, and MBL2 as potential AS biomarkers for the first time. The expression levels of MMP3, C9, and CFHR5 were verified in AS SF using western blotting. CONCLUSION: We performed quantitative comparative proteomic analysis using by LC-MS/MS of the SF from four disease states: RA, gout, and OA. This systematic comparison revealed novel differentially expressed proteins in AS SF, as well as two previously reported candidate biomarkers. We further verified the expression of MMP3, C9 and CFHR5 by western blot. These proteins may serve as diagnostic or prognostic biomarkers in patients with AS, and may thus improve the clinical outcomes of this serious disease.