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1.
Medicine (Baltimore) ; 99(31): e21450, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756165

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is a common progressive autoimmune inflammatory disease. Du moxibustion can effectively treat AS with few adverse reactions. The aim of this protocol is to systematically investigate the effectiveness and safety for management of AS with Du moxibustion. METHODS: Seven relevant databases, namely, PubMed, Cochrane Library, Embase, Chinese Biomedical Literatures Database (CBM), China National Knowledge Infrastructure (CNKI), WangFang Database (WF), Chinese Scientific Journal Database (VIP) will be searched from their inception until May 1st, 2020. All clinical randomized controlled trials containing eligible interventions(s) and outcome(s) will be included, regardless of blinding or publication types. Two reviewers will independently retrieval databases, extract data, and then assess the quality of studies. Data synthesis will be conducted by RevMan 5.3 software. We regard the effective rate, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Visual Analogue Scale (VAS) as the primary outcomes, and the secondary outcomes contain C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), finger-to-floor distance (FFD), occiput to wall distance (OWD), and side effects. The result about the curative effect and safety of Du moxibustion for AS will be presented as risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data. RESULTS: The finding will be presented in a journal or related conferences. CONCLUSIONS: This study expects to provide high-quality, evidence-based recommendations on further treatment for clinical guidance. PROSPERO REGISTRATION NUMBER: CRD42020158727.


Assuntos
Moxibustão/métodos , Espondilite Anquilosante/sangue , Espondilite Anquilosante/terapia , Sedimentação Sanguínea , Proteína C-Reativa/análise , Bases de Dados como Assunto , Humanos , Moxibustão/efeitos adversos , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Espondilite Anquilosante/epidemiologia , Resultado do Tratamento , Escala Visual Analógica
2.
Medicine (Baltimore) ; 99(15): e19806, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282746

RESUMO

RATIONALE: Acute lymphoblastic leukemia (ALL) has acute and severe onset characterized by fever, moderate to severe anemia, bone and joint pain, and sternal tenderness. It is easy to be misdiagnosed as rheumatic disease when joint pain is the first symptom. PATIENT CONCERNS: A male Han, 18 years of age was admitted on July 15th, 2016 for multi-joint swelling and pain with intermittent fever for half a year which had aggravated in the last 10 days. DIAGNOSIS: Based on symptoms, imaging, family history, and blood tests, he was first diagnosed with ankylosing spondylitis, but he was refractory to treatment. Bone marrow biopsy then revealed acute B-lymphoblastic leukemia (possibility Pro-B-ALL). INTERVENTIONS: The patient was transferred to the hematology department on July 23rd, 2016 for chemotherapy. OUTCOMES: No joint pain occurred during follow-up, which ended on November 4th, 2018. LESSONS: ALL may present with symptoms suggestive of rheumatic diseases like ankylosing spondylitis. Physicians should be aware of this possibility, especially in young patients.


Assuntos
Artralgia/etiologia , Leucemia Linfocítica Crônica de Células B/patologia , Espondilite Anquilosante/diagnóstico , Adolescente , Antineoplásicos/uso terapêutico , Artralgia/diagnóstico , Biópsia , Medula Óssea/patologia , Diagnóstico Diferencial , Erros de Diagnóstico , Febre/diagnóstico , Febre/etiologia , Humanos , Artropatias/diagnóstico por imagem , Artropatias/patologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Espondilite Anquilosante/sangue , Espondilite Anquilosante/terapia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
3.
Clin Chim Acta ; 505: 136-140, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32112798

RESUMO

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.


Assuntos
Albuminas/análise , Fibrinogênio/análise , Espondilite Anquilosante/sangue , Adulto , Área Sob a Curva , Biomarcadores/sangue , Feminino , Humanos , Contagem de Linfócitos , Masculino , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Valores de Referência , Estudos Retrospectivos
4.
Trials ; 21(1): 13, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907007

RESUMO

BACKGROUND: Infliximab (INX) and other tumour necrosis factor inhibitors (TNFi) have revolutionised the treatment of several immune mediated inflammatory diseases. Still, many patients do not respond sufficiently to therapy or lose efficacy over time. The large interindividual variation in serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be major reasons for treatment failures. Therapeutic drug monitoring (TDM), an individualised treatment strategy based on systematic assessments of serum drug concentrations, has been proposed as a clinical tool to optimise efficacy of INX treatment. TDM seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy has not yet been demonstrated in randomised clinical trials. The NORwegian DRUg Monitoring study (NOR-DRUM) aims to assess the effectiveness of TDM, both with regard to the achievement of remission in patients starting INX treatment (part A) as well as to maintain disease control in patients on INX treatment (part B). METHODS: The NOR-DRUM study is a randomised, open, controlled, parallel-group, comparative, multi-centre, national, superiority, phase IV study with two separate parts, NOR-DRUM A and NOR-DRUM B. Patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, ulcerative colitis, Crohn's disease and psoriasis are included. In both study parts participants are randomised 1:1 to either TDM of infliximab (intervention group) or to standard treatment with infliximab without knowledge of drug levels or ADAb status (control group). NOR-DRUM A will include 400 patients starting INX therapy. The primary outcome is remission at 30 weeks. In NOR-DRUM B, 450 patients on maintenance treatment with INX will be included. The primary endpoint is occurrence of disease worsening during the 52-week study period. DISCUSSION: As the first trial to assess the effectiveness, safety and cost-effectiveness of TDM in patients receiving TNFi for a range of immune mediated inflammatory diseases, we hope that the NOR-DRUM study will contribute to the advancement of evidence based personalised treatment with biological medicines. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03074656. Registered on 090317.


Assuntos
Antirreumáticos/uso terapêutico , Monitoramento de Medicamentos , Infliximab/uso terapêutico , Adulto , Idoso , Antirreumáticos/farmacocinética , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Ensaios Clínicos Fase IV como Assunto , Colite Ulcerativa/sangue , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Infliximab/farmacocinética , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Noruega , Psoríase/sangue , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Espondilite Anquilosante/sangue , Espondilite Anquilosante/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
5.
Sci Rep ; 10(1): 1412, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996699

RESUMO

Lymphotoxin-a (LTA) may be associated with the pathogenesis of inflammatory diseases. To assess the association of the LTA rs909253 A/G polymorphism with plasma level and risk of ankylosing spondylitis (AS) in a Chinese Han population. Genotyping and LTA plasma were tested by mass spectroscopy and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that the average plasma level of LTA in AS was significantly lower than in the controls (P = 0.000). Our results also indicated that LTA rs909253 A/G was associated with a decreased risk of AS (G vs. A: P = 0.014). Significant differences were also found between the rs909253 A/G genotype and down-regulated plasma level in AS patients, compared with controls. After stratification analysis, a decreased risk of AS was associated with the LTA rs909253 G allele (G vs. A) among female patients, younger patients (Yr. < 30), HLA-B27-positive patients. In addition, In conclusion, LTA rs909253 A/G genotype has a significant relationship with decreased susceptibility to AS.


Assuntos
Linfotoxina-alfa/genética , Espondilite Anquilosante/genética , Adulto , Fatores Etários , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Técnicas de Genotipagem , Antígeno HLA-B27/sangue , Antígeno HLA-B27/imunologia , Humanos , Linfotoxina-alfa/sangue , Masculino , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Espondilite Anquilosante/sangue , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/imunologia , Adulto Jovem
6.
Clin Chim Acta ; 503: 197-202, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31794766

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease with high disability rate, and it is sometimes difficult to distinguish from generalized osteoarthritis (GOA). Deoxyribonuclease 1-like 3 (DNASE1L3) was associated with a variety of autoimmune diseases. However, the serum DNASE1L3 level in AS and GOA remain unreported. Herein, this study was designed to gauge serum DNASE1L3 level in patients with AS and GOA, and to discern the utility of serum DNASE1L3 as a biomarker for assessing the severity of patients with AS. METHODS: The study population consisted of 60 patients with AS, 60 patients with GOA and 60 control subjects. Serum DNASE1L3 levels were measured using enzyme-linked immunosorbent assay (ELISA) assay. Disease activity were assessed with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS patients. RESULTS: Our data showed that serum DNASE1L3 levels were significantly higher in patients with AS than that of the healthy controls and patients with GOA. Serum DNASE1L3 levels in patients with AS were positively correlated with BASDAI scores, C3 and C-reactive protein (CRP). Furthermore, serum DNASE1L3 showed higher discriminatory accuracy in the diagnosis of AS from GOA (AUC = 0.851, sensitivity = 78.33% and specificity = 81.67%). CONCLUSIONS: Elevated Serum DNASE1L3 levels in patients with AS were significantly associated with the clinic features and disease activity. DNASE1L3 could be a serum biomarker with a positive diagnostic value in patients with AS, and which could be used as a differential diagnostic indicator for GOA and AS.


Assuntos
Endodesoxirribonucleases/sangue , Espondilite Anquilosante/diagnóstico , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Complemento C3/análise , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/sangue , Osteoartrite/diagnóstico , Espondilite Anquilosante/sangue
7.
Rheumatology (Oxford) ; 59(5): 1159-1169, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31846044

RESUMO

OBJECTIVE: Bone loss is common in AS, and miR-214 plays an important role in regulating bone formation. The aim of this study was to investigate the effect of miR-214, the production of which is stimulated by IL-17A, on bone loss in AS. METHODS: Peripheral blood was obtained from 32 patients with AS and 24 healthy controls. Levels of IL-17A, soluble RANK ligand (RANKL) and osteoprotegerin in serum were evaluated by ELISA, and the relative level of miR-214 in serum was detected by real-time quantitative PCR. In addition, we assessed the relationship between levels of miR-214, IL-17A and bone loss in primary murine osteoblasts and mouse bone marrow cells. RESULTS: The expression of RANKL and miR-214 in osteoblasts was increased following stimulation by IL-17A, and osteoblasts stimulated by IL-17A promoted the expression of miR-214 in osteoclasts and the activity of osteoclasts. We showed that osteoblast-derived miR-214 could be transferred to osteoclasts and could then regulate their activity. The levels of IL-17A and miR-214 were much higher in the serum of patients with AS than in that of healthy controls, and the relative level of miR-214 was positively correlated with the level of IL-17A in the serum and synovial fluid of the patients with AS, not healthy controls. The level of miR-214 in the serum of AS patients has potential diagnostic value. CONCLUSION: The production of miR-214 in osteoblasts is stimulated by IL-17A. It is an important inhibitor of bone formation in AS, and the serum level of miR-214 might be of potential diagnostic value for AS.


Assuntos
Interleucina-17/metabolismo , Osteogênese , Ligante RANK/metabolismo , Espondilite Anquilosante/sangue , Espondilite Anquilosante/metabolismo , Animais , Reabsorção Óssea , Estudos de Casos e Controles , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Camundongos , MicroRNAs/metabolismo , Osteoclastos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Pesquisa Médica Translacional
8.
Immunol Lett ; 217: 31-38, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31711818

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is a prototype of chronic inflammatory arthritis termed seronegative spondyloarthropathies that typically affects the joints. Among the non-Human leukocyte antigen (HLA) loci, the strongest association has been observed with Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene single nucleotide polymorphisms (SNPs). Moreover, the effect of ERAP1 gene SNPs on the pro-inflammatory and anti-inflammatory cytokines in AS disease has still been poorly elucidated. In this study, we aimed to determine the association of ERAP1 gene SNPs (rs30187 and rs2287987) with AS risk as well as their effect on the mRNA expression of pro-inflammatory and anti-inflammatory cytokines, with emphasis on the immunoregulation of the IL-17/IL-23 pathway, in an Iranian population. METHODS: We performed Single specific primer (SSP)-PCR for genotyping of 160 AS patients and 160 healthy controls. After isolation of peripheral blood mononuclear cells (PBMCs), total RNA of PBMCs was isolated, complementary DNA (cDNA) was synthesized, and quantitative analyses of mRNA expression of cytokines were performed by Real-time PCR for 40 HLA-B27 positive AS patients and 40 healthy individuals as controls. RESULTS: It was seen that T allele of rs30187 (OR = 1.54, 95% CI = 1.07-2.22, P =  0.017) and C allele of rs2287987 (OR 1.50, 95% CI 1.05-2.14, P = 0.024) were associated with the risk of AS. Both of these alleles were associated more strongly in the HLA-B27 positive AS patients. There was a significant overexpression of mRNAs of pro-inflammatory (IL-17A, IL-17F, IL-23, TNF-α and IFN-γ), while downregulation of anti-inflammatory cytokines (IL-10 and TGF-ß) in PBMCs from 40 HLA-B27 positive AS patients in comparison to controls. AS patients with rs30187 SNP TT genotype expressed mRNA of IL-17A, IL-17F, and IL-23 significantly higher than patents with CT and CC genotypes for this SNP. CONCLUSIONS: This study represented the association of ERAP1 gene rs30187 and rs2287987 polymorphism with the risk of AS. Additionally, it appears that rs30187 polymorphism may be involved in the immunomodulation of the IL-17/IL-23 pathway in the AS disease.


Assuntos
Aminopeptidases/genética , Citocinas/sangue , Antígeno HLA-B27/sangue , Leucócitos Mononucleares/metabolismo , Antígenos de Histocompatibilidade Menor/genética , Espondilite Anquilosante/genética , Adulto , Alelos , Aminopeptidases/imunologia , Estudos de Casos e Controles , Citocinas/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Interferon gama/sangue , Interferon gama/genética , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-17/sangue , Interleucina-17/genética , Interleucina-23/sangue , Interleucina-23/genética , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor/imunologia , Polimorfismo de Nucleotídeo Único , Espondilite Anquilosante/sangue , Espondilite Anquilosante/enzimologia , Espondilite Anquilosante/imunologia , Fator de Crescimento Transformador beta/sangue , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Adulto Jovem
9.
Mod Rheumatol ; 30(4): 648-656, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31370733

RESUMO

Objectives: The aim of the present study was to investigate the differences in clinic-pathological features of secondary IgA nephropathy (SIgAN) between patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA).Methods: Forty-six patients with SIgAN related to AS (SIgAN-AS) and 26 patients with SIgAN related to RA (SIgAN-RA) were enrolled in this retrospective study. The two groups were compared for their clinic-pathological characteristics.Results: The 10-year prevalence of SIgAN-AS and SIgAN-RA were 167 per 1000 and 51.3 per 1000, respectively. Compared with SIgAN-RA patients, SIgAN-AS patients had lower incidences of edema and nephrotic syndrome, but higher levels of eGFR, serum C3, and CD3- and CD8-positive T-cell counts, but less incidences of acute tubulointerstitial lesions and interlobular arterial lesions. IgM was the most familiar co-depositing immune complex on tissue with significantly different frequencies. In SIgAN-AS patients, those with positive HLA-B27 presented with lower levels of proteinuria, higher levels of serum IgG and C3, and less incidence of renal insufficiency, crescents >14.5%, glomerular sclerosis >32.6% and segmental sclerosis >5.2%.Conclusion: SIgAN was more prevalent in AS than in RA. SIgAN-AS patients differed from SIgAN-RA patients in certain clinic-pathological characteristics. HLA-B27 likely protected SIgAN-AS patients from renal insufficiency.


Assuntos
Artrite Reumatoide/complicações , Glomerulonefrite por IGA/sangue , Espondilite Anquilosante/complicações , Adulto , Artrite Reumatoide/sangue , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/epidemiologia , Glomerulonefrite por IGA/patologia , Antígeno HLA-B27/sangue , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/sangue
10.
Mod Rheumatol ; 30(2): 373-378, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30922195

RESUMO

Objectives: To investigate associations of serum melatonin with spinal ossification and cytokines in ankylosing spondylitis (AS).Methods: Serum was obtained from 52 AS patients and 25 healthy controls. Melatonin was measured by ELISA kit; bone morphogenetic protein (BMP)-2, dickkopf-related protein (Dkk)-1, IL-1ß, IL-6, IL-17 and TNF-α concentrations were assayed using Luminex multiplex bead system. Osteocalcin and ß isomer of C-terminal telopeptide of type I collagen (ß-CTX) were measured using electrochemiluminescence immunoassay. Spinal damages were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) on radiographs.Results: Serum melatonin was significantly increased in AS patients. Serum melatonin correlated positively with mSASSS after multivariate adjustment for age and disease duration (r = 0.70, p < .01). Patients with spinal bone bridge have higher levels of melatonin than those without spinal bone bridge [16.69 (4.65, 41.10) pg/ml vs. 7.43 (3.29, 15.30) pg/ml, p = .03]. The multiple linear regression analysis found that melatonin was a risk factor for spinal bone formation (ß = 0.35, p < .05). Additionally, melatonin correlated positively with osteocalcin (r = 0.34, p = .04) and IL-1ß (r = 0.39, p = .04) in AS.Conclusion: Melatonin is increased in AS patients, especially in patients with spinal bone bridge. It suggests that melatonin may play an important role in the pathological osteogenesis of AS.


Assuntos
Melatonina/sangue , Ossificação Heterotópica/sangue , Espondilite Anquilosante/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/patologia , Radiografia , Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/patologia
11.
Clin Rheumatol ; 39(1): 167-175, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31522318

RESUMO

OBJECTIVES: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS. PATIENTS AND METHODS: Thirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (ßCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months. RESULTS: TNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/ßCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and ßCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline ßCTX, while femoral neck BMD rather showed inverse correlations with CRP. CONCLUSIONS: Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and ßCTX in RA, whilst CRP in AS.Key Points• One-year anti-TNF therapy halted generalized bone loss in association with clinical improvement in arthritides.• Anti-TNF therapy may inversely act on DKK-1 and SOST.• Independent predictors of BMD were SOST and ßCTX in RA, while CRP in AS.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Densidade Óssea/efeitos dos fármacos , Certolizumab Pegol/uso terapêutico , Etanercepte/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Absorciometria de Fóton , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/sangue , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Espondilite Anquilosante/sangue , Adulto Jovem
12.
Med Sci Monit ; 25: 9702-9711, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31851643

RESUMO

BACKGROUND This study was to investigate the correlation between osteoporosis and serum uric acid in ankylosing spondylitis (AS) patients, and to further identify potential factors that might be associated with osteoporosis in AS patients. MATERIAL AND METHODS We included 182 AS patients, consisted of 143 male patients and 39 female patients, who visited our hospital from January 1, 2014 to December 31, 2018. We used dual-energy x-ray absorptiometry to measure bone mineral density (BMD) of orthotopic lumbar vertebrae in patients with AS. The gender, age, disease duration, BMD, T-score, Z-score, uric acid, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood platelet (PLT), and status of treatment with biologics of the patients were collected. Then, the Spearman correlation coefficient and multivariate liner regression analysis were applied to identify the relationship between the factors and BMD, T-score, and Z-score in AS patients. RESULTS Male AS patients between the ages of 16 and 30 years old had a higher risk of osteoporosis (P<0.05). AS patients with uric acid value between 300-360 µmol/L had the highest BMD, T-score, and Z-score. The BMD had a positive correlation with age and disease duration (P<0.01) while had a negative correlation with PLT (P<0.05). BMD in AS patients with elevated ESR was significantly (P<0.05) lower than in AS patients with normal ESR. There were no significant differences in BMD between AS patients with elevated CRP and the patients with normal CRP and PLT. Treatment with TNFi (tumor necrosis factor alpha inhibitor) did not improve BMD in AS patients. CONCLUSIONS The relationship between uric acid and BMD in AS patients was observed as inverted "U"-type. Keeping uric acid within 300-360 µmol/L might be helpful in preventing AS patients from developing osteoporosis.


Assuntos
Grupo com Ancestrais do Continente Asiático , Osteoporose/sangue , Osteoporose/complicações , Espondilite Anquilosante/sangue , Espondilite Anquilosante/complicações , Ácido Úrico/sangue , Adolescente , Adulto , Antirreumáticos/uso terapêutico , Plaquetas/metabolismo , Sedimentação Sanguínea , Densidade Óssea , Proteína C-Reativa/metabolismo , Feminino , Humanos , Inflamação/sangue , Inflamação/patologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoporose/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/fisiopatologia , Adulto Jovem
13.
Dis Markers ; 2019: 2073139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772684

RESUMO

This study is aimed at exploring the levels of peripheral blood circular RNAs (circRNAs) as biomarker candidates for the diagnosis of new-onset rheumatoid arthritis (RA). The selected twenty-two circRNAs in peripheral blood from new-onset RA patients and healthy controls (HC) were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The levels of hsa_circ_0002715, hsa_circ_0001947, hsa_circ_0000367, and hsa_circ_0035197 were significantly increased in the peripheral blood of new-onset RA patients than in the peripheral blood of HC. And, there were obvious differences in the above four peripheral blood circRNAs between new-onset RA patients and systemic lupus erythematosus (SLE) patients and ankylosing spondylitis (AS) patients. Moreover, there were obvious differences in hsa_circ_0001947 and hsa_circ_0035197 between new-onset RA patients and patients with undiagnosed arthritis (UA). Receiver operating characteristic (ROC) curve analysis suggested that the levels of hsa_circ_0002715 and hsa_circ_0000367 in peripheral blood could distinguish new-onset RA patients from the HC, AS patients, and SLE patients, and the levels of hsa_circ_0001947 and hsa_circ_0035197 in peripheral blood could distinguish new-onset RA patients from the HC, AS patients, SLE patients, and UA patients. The logistic regression model showed that the combination of hsa_circ_0002715 and hsa_circ_0035197 could provide the best diagnostic accuracy with an area under the curve (AUC) of 0.758 (sensitivity: 72.9%, specificity: 71.4%). Moreover, the levels of peripheral blood hsa_circ_0002715 were correlated with swollen joint count (SJC), tender joint count (TJC), disease duration, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA), and hematologic disorder. And, the levels of peripheral blood hsa_circ_0035197 were correlated with hematologic disorder. This study suggests that the combination of hsa_circ_0002715 and hsa_circ_0035197 in peripheral blood may be a potential biomarker of patients with new-onset RA and may be associated with disease activity.


Assuntos
Artrite Reumatoide/genética , Biomarcadores/sangue , RNA Circular/sangue , Adulto , Área Sob a Curva , Artrite Reumatoide/sangue , Artrite Reumatoide/etiologia , Autoanticorpos/sangue , Estudos de Casos e Controles , Expressão Gênica , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Pessoa de Meia-Idade , Fator Reumatoide/sangue , Espondilite Anquilosante/sangue , Espondilite Anquilosante/genética
14.
Int J Rheum Dis ; 22(12): 2206-2212, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31721427

RESUMO

INTRODUCTION: The Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) are commonly used instruments for measuring disease activity. However, few studies have assessed their psychometric properties in patients with axial spondyloarthritis (axSpA). We aimed to assess the validity and reliability of ASDAS-CRP and BASDAI in patients with axSpA in Singapore. METHODS: Cross-sectional data from 280 patients with axSpA from a dedicated axSpA clinic in a Singapore tertiary referral hospital from 2011 to 2019 were used. Internal consistency was assessed using Cronbach's alpha. Construct validity was assessed through 12 a priori hypotheses by correlation of overall ASDAS-CRP and BASDAI score with other patient-reported outcomes measures (PROMs). Structural validity was evaluated via confirmatory factor analysis using maximum-likelihood method, where Comparative Fit Index (CFI) >0.95, Tucker-Lewis Index (TLI) >0.95, Root Mean Square Error of Approximation (RMSEA) <0.06 and Standardized Root Mean Residuals (SRMR) <0.08 were indicative of good fit. RESULTS: Among 280 patients (78.2% Male; 92.5% Chinese), ASDAS-CRP showed poor internal consistency of 0.33, while BASDAI showed high internal consistency of 0.87. Convergent and divergent construct validity were demonstrated by fulfillment of 11 out of 12 a priori hypotheses when ASDAS-CRP and BASDAI were compared with other PROMs. Our proposed ASDAS-CRP and BASDAI model showed good fit for a 1-factor structure respectively (CFI = 0.993, TLI = 0.984, RMSEA = 0.036, SRMR = 0.026 for ASDAS-CRP; CFI = 0.993, TLI = 0.985, RMSEA = 0.057, SRMR = 0.022 for BASDAI), demonstrating structural validity. CONCLUSION: This study supports the use of both ASDAS-CRP and BASDAI in measuring disease activity in patients with axSpA in Singapore.


Assuntos
Proteína C-Reativa/análise , Indicadores Básicos de Saúde , Mediadores da Inflamação/sangue , Espondilite Anquilosante/diagnóstico , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Singapura , Espondilite Anquilosante/sangue , Espondilite Anquilosante/imunologia , Adulto Jovem
15.
Ann Clin Lab Sci ; 49(5): 611-618, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31611204

RESUMO

OBJECTIVE: The objective of this study is to investigate the baseline predictors of clinical response from tumor necrosis factor (TNF) inhibitor within ankylosing spondylitis (AS) patients. METHODS: We selected 60 AS patients and 24 healthy individuals. The interleukin (IL)-1ß, IL-6, IL-17A and TNF-α levels were measured using the cytometric bead array. The receiver operating characteristic curve was used to analyze the cut off values of baseline predictors. A binary logistic regression test was used to investigate the association between baseline predictors and clinical response. RESULTS: At baseline, the IL-1ß, IL-6 and TNF-α level were positively correlated with disease activity. After 12 weeks of treatment, good responders had lower baseline IL-6 level and erythrocyte sedimentation rate (ESR) than non/poor responders. The cut off value of baseline IL-6 level and ESR to predict clinical response of TNF inhibitor treatment were 9.05 pg/mL and 47.00 mm/h, respectively. Binary logistic regression found that baseline IL-6 levels and ESR had an adverse relationship with clinical response, and the combination of IL-6 level and ESR could predict clinical response more effectively. CONCLUSIONS: The baseline IL-6 level and ESR can predict the clinical response of TNF inhibitor treatment within AS patients, which might facilitate the selection and adjustment of medication regimens for subjects.


Assuntos
Interleucina-6/sangue , Espondilite Anquilosante/sangue , Espondilite Anquilosante/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Curva ROC , Resultado do Tratamento
16.
Harefuah ; 158(9): 568-570, 2019 Sep.
Artigo em Hebraico | MEDLINE | ID: mdl-31507105

RESUMO

AIMS: To examine statistical correlation between mSASSS and serum levels of testosterone in males suffering from AS. BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive inflammatory rheumatic disease primarily involving sacroiliac joints and spine. Structural damage, caused by AS, manifests with development of vertebral syndesmophytes and can be calculated as units of modified Spinal Ankylosing Spondylitis Syndesmophyte Score (mSASSS). The rate of growth of spinal syndesmophytes differs among individual AS patients, while male patients develop significantly more structural damage compared to females in general. METHODS: Twenty males with AS known for at least 5 years (average disease duration 12.8 years) and aged between 25 to 40 years donated 5 ml of peripheral blood for serum testosterone assay, and underwent X-ray films of cervical and lumbar spine. The mSASSS was calculated and correlation with serum testosterone levels was examined using Pearson correlation test. RESULTS: The mSASSS values of patients included in the final analysis ranged from 0-14 units and testosterone levels ranged from 8.4-25.5 nmol/L. No significant correlation was found between mSASSS values and testosterone levels in this cohort. CONCLUSIONS: This study did not find statistical correlation between mSASSS and serum levels of testosterone in males suffering from AS.


Assuntos
Espondilite Anquilosante/sangue , Testosterona/sangue , Adulto , Progressão da Doença , Feminino , Humanos , Vértebras Lombares , Masculino , Radiografia , Índice de Gravidade de Doença , Coluna Vertebral
17.
J Orthop Surg Res ; 14(1): 313, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533751

RESUMO

BACKGROUND: This study aimed to assess the efficacy of water-filtered infrared A (wIRA) in sacroiliitis in male patients with ankylosing spondylitis (AS) and the effect of wIRA therapy on serum vascular endothelial growth factor (VEGF). METHODS: One hundred twenty male AS patients with active sacroiliitis were randomly divided into wIRA group and control group. wIRA treatment was performed twice daily for 5 consecutive days with 24-h interval before switching the treatment (crossover design). Bath ankylosing spondylitis disease activity index (BASDAI) scores, pain visual analogue scale (VAS), and morning stiffness VAS were recorded prior to and after each treatment period. Additionally, C-reactive protein (CRP), serum VEGF, and resistance index (RI) of sacroiliac joints detected by ultrasonography were recorded at baseline and after the first and second treatment period, respectively. The efficacy was examined by using repeated measures analysis of variance (ANOVA). RESULTS: BASDAI, pain VAS, and morning stiffness VAS scores decreased significantly (P < 0.001) after wIRA treatment and no-wIRA treatment (control group), and the difference between the two groups was significant (P < 0.001). CRP declined and RI increased during the wIRA treatment as compared with the no-wIRA treatment (P < 0.001). The increase in RI was associated with improvement of pain VAS scores (P = 0.018), while serum VEGF was unaffected by the treatment. CONCLUSIONS: wIRA treatment achieved symptom and pain relief for AS patients with active sacroiliitis. wIRA treatment also improved RI revealed by ultrasonography, and this effect was associated with improved pain VAS scores.


Assuntos
Raios Infravermelhos/uso terapêutico , Sacroileíte/radioterapia , Espondilite Anquilosante/radioterapia , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Proteína C-Reativa/metabolismo , Estudos Cross-Over , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Amplitude de Movimento Articular , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/fisiopatologia , Sacroileíte/sangue , Sacroileíte/diagnóstico por imagem , Sacroileíte/fisiopatologia , Índice de Gravidade de Doença , Espondilite Anquilosante/sangue , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/fisiopatologia , Resultado do Tratamento , Ultrassonografia , Adulto Jovem
18.
Sci Rep ; 9(1): 11218, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375691

RESUMO

Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A total of 193 axSpA patients (nr-axSpA, n = 121 and AS, n = 72) and asymptomatic controls (n = 100) were included. Serum levels of metalloproteinase (MMP)-degraded collagen type I (C1M), type II (C2M), type III (C3M) and type IV (C4M2) were quantified by enzyme-linked immunosorbent assay (ELISA). All metabolites were higher in axSpA than in controls (all p < 0.001). Serum levels of C1M, C3M, and C4M2 were increased in AS compared to nr-axSpA (43.4 ng/mL vs. 34.6; p < 0.001, 15.4 vs. 12.8; p = 0.001, and 27.8 vs. 22.4; p < 0.001). The best metabolite to differentiate between axSpA and controls was C3M (AUC 0.95; specificity 92.0, sensitivity 83.4). C1M correlated with ASDAS-CRP in nr-axSpA (ρ = 0.37; p < 0.001) and AS (ρ = 0.57; p < 0.001). C1M, C3M, and C4M2 were associated with ASDAS-CRP in AS and nr-axSpA after adjustment for age, gender, and disease duration. Serum levels of collagen metabolites were significantly higher in AS and nr-axSpA than in controls. Moreover, the present study indicates that collagen metabolites reflect disease activity and are useful biomarkers of axSpA.


Assuntos
Colágenos Fibrilares/metabolismo , Espondilartrite/diagnóstico , Adulto , Biomarcadores/sangue , Colágeno Tipo I/metabolismo , Colágeno Tipo II/metabolismo , Colágeno Tipo III/metabolismo , Colágeno Tipo IV/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Espondilartrite/sangue , Espondilite Anquilosante/sangue , Espondilite Anquilosante/diagnóstico
19.
Ann Biol Clin (Paris) ; 77(4): 453-458, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31418707

RESUMO

Infliximab (IFX) is a chimeric monoclonal antibody which has proven its efficacy in the treatment of inflammatory diseases. However, its efficacy can be limited by the development of anti-IFX antibodies (ATI) resulting in a therapeutic failure of IFX. ATI plasmatic monitoring is then indicated to optimize IFX treatment. The aim of this study was to validate an ELISA (enzyme linked immuno sorbent assay) method of ATI plasmatic monitoring. METHODS: Assessment of performance was based on the study of correlation and concordance (Bland Altman method) of the absorbances measured by the two readers. ELISA kit validation was made by calculating the accuracy and the exactitude. RESULTS: We collected 23 samples. Their mean age was 46 years and sex ratio M/W was 0.92. In nine cases, plasmatic AIT were positive and in 14 cases, they were not detected. Correlation between the two readers showed a correlation coefficient r2 of 99.95%. Concordance limits of the confidence interval 95% were [-112.768%-41.425%] with a bias of -35.671%. Repeatability and reproductibility were checked by a positive control and coefficients of variation were respectively of 5.574% and 14.184%. Limits of detection and quantification were respectively of 0.046 and 0.086. The positive predictive value was 0.5 and the negative predictive value was 1. The sensitivity was 100% and the specificity was 83%. CONCLUSION: The assessment of the performance of the tested microplate reader and the validation of the tested ELISA kit showed good results allowing ATI routine measurement to optimize therapeutic management of patients treated by IFX.


Assuntos
Anticorpos Monoclonais/sangue , Infliximab/imunologia , Kit de Reagentes para Diagnóstico , Testes Sorológicos/métodos , Adulto , Anticorpos Monoclonais/análise , Monitoramento de Medicamentos/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Kit de Reagentes para Diagnóstico/normas , Doenças Reumáticas/sangue , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/tratamento farmacológico , Sensibilidade e Especificidade , Espondilite Anquilosante/sangue , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/tratamento farmacológico
20.
J Interferon Cytokine Res ; 39(9): 572-576, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31347941

RESUMO

Etiopathogenesis of ankylosing spondylitis (AS), a major subtype of a group of chronic inflammatory diseases known as spondyloarthropathies, is not clearly understood yet. In this study, we aimed to investigate the interleukin 23 (IL-23)/interleukin-17 (IL-17) pathway, which is a new cytokine pathway in inflammatory diseases. We evaluated serum IL-17 and IL-23 levels after 1-year follow-up in AS patients using only nonsteroidal anti inflammatory drugs (at need or continue). Forty-four AS patients and 40 healthy controls were included in the study. Clinical evaluations of disease activity were performed. Serum tumor necrosis factor-α (TNF-α), IL-6, IL-17, and IL-23 levels were evaluated. IL-17 and IL-23 levels of the patient group at baseline and 12 months were lower than the control group. There was no significant difference between the baseline and 12th month evaluations of the patient group. TNF-α levels were similar in all groups (in the baseline and 12th month of the patient group and in the control group). Although our results are in contrast to the literature findings, the IL-23/IL-17 pathway is a newly discovered pathway, and there may still be unknowns. New studies involving larger patient groups are needed for the factors affecting serum IL-23/IL-17 levels in patients with AS. We also think that it will be useful to make more comprehensive and long-term studies about which patients will respond well to IL-23/IL-17 blockade.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Interleucina-17/sangue , Interleucina-23/sangue , Espondilite Anquilosante/sangue , Espondilite Anquilosante/tratamento farmacológico , Adulto , Estudos de Coortes , Feminino , Humanos , Interleucina-17/imunologia , Interleucina-23/imunologia , Masculino , Estudos Prospectivos , Espondilite Anquilosante/imunologia
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