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Avacopan, a C5a receptor (C5aR) inhibitor, has emerged as a novel treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV), providing an alternative to glucocorticoids (GCs).1 Despite its promising potential, severe liver dysfunction associated with avacopan has been reported in Japan.2,3.
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OBJECTIVE: This study clarifies the involvement of gender and pre-existing diabetes mellitus (DM) in the clinical characteristics of polymyalgia rheumatica (PMR). METHODS: The clinical records of patients diagnosed with PMR in our department between January 2011 and June 2021, especially in terms of gender and DM were retrospectively analysed. RESULTS: We identified 89 patients with the median age of 75.37 cases were men and 52 cases were women. Pre-existing DM was found in 21 patients (23.6%). Male PMR patients exhibited a higher complication rate of pre-existing DM and C-reactive protein (CRP) levels at diagnosis (p = .04 and p < .01, respectively) than female patients, and men were more common in the patient group with pre-existing DM (p = .04). The CRP levels of male PMR patients without pre-existing DM were higher than female PMR patients without pre-existing DM. CONCLUSION: Male PMR patients might have a varying pathophysiology from female patients in terms of high inflammation levels accompanied by a high prevalence rate of pre-existing DM and need a gender-specific approach.
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Diabetes Mellitus , Arterite de Células Gigantes , Polimialgia Reumática , Humanos , Masculino , Feminino , Polimialgia Reumática/complicações , Polimialgia Reumática/epidemiologia , Polimialgia Reumática/diagnóstico , Estudos Retrospectivos , População do Leste Asiático , Arterite de Células Gigantes/complicações , Diabetes Mellitus/epidemiologiaRESUMO
OBJECTIVE: We aimed to compare life prognosis and renal relapse after induction therapy in proliferative (PLN) and pure membranous LN (MLN). METHODS: We retrospectively analysed the cases of 140 of 172 patients with LN who underwent a renal biopsy at our hospital or community hospitals from 1993 to 2016. We determined the complete response (CR) rate at 12 months after the patients had started induction therapy, and we evaluated the predictive factors for CR, life prognosis and renal relapse in PLN and pure MLN. We defined PLN as International Society of Neurology and the Renal Pathology Society (ISN/RPS) Class III or IV and MLN as ISN/RPS Class V. RESULTS: The renal pathology of 99 (70.7%) patients was classified as PLN, and that of the other 41 (29.3%) patients as MLN. Fifty patients (50.5%) with PLN and 22 patients (53.7%) with MLN achieved a CR at 12 months. A multivariate analysis showed that a lower index of chronicity in PLN and a higher total haemolytic complement (CH50) level in MLN were predictive factors for achieving a CR at 12 months. A Kaplan-Meier analysis showed that the life prognosis (P = 0.93) and renal relapse (P = 0.52) were not significantly different between PLN and MLN. CONCLUSIONS: The predictive factors for a CR at 12 months post-induction therapy were index of chronicity in PLN and CH50 level in MLN. There were no significant differences in life prognosis or renal relapse between PLN and MLN in the achievement of a CR at 12 months post-induction therapy.
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Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Quimioterapia de Indução , Nefrite Lúpica/tratamento farmacológico , Adulto , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos RetrospectivosRESUMO
OBJECTIVES: To investigate the utility of 18F-FDG PET/CT in the diagnostic procedure of IgG4-related disease (IgG4-RD), we analysed the association between quantitative method of 18F-FDG PET/CT and histological findings. METHODS: Twenty-one patients with IgG4-RD in whom 18F-FDG PET/CT was performed at the time of diagnosis were enrolled. Tissue biopsy was performed at 24 sites in 21 patients. To perform quantitative analysis of 18F-FDG PET/CT imaging, the highest standardised uptake value (SUV) of the pixels (SUVmax) and the average SUV (SUVmean) within the biopsied lesion were measured. The SUVmean of the liver was also measured as a reference. RESULTS: The mean age at diagnosis was 64.6±11.9 years, and the median serum IgG4 level was 650 mg/dl. Histological findings were consistent with IgG4-RD (histopathology-positive) at 19 out of 24 sites. Although there was no significant difference in the values of SUVmax between histopathology-positive and histopathology-negative tissues, the values of SUVmean were significantly higher in the histopathology-positive tissue (4.98 and 3.54, respectively p<0.05). The values of SUVmean/liver were also higher in the histopathology-positive tissue (2.17 and 1.52, respectively p<0.05). To establish a cut-off value of SUVmean to determine which of multiple lesions should be biopsied, a ROC curve was constructed. ROC curve analysis indicated SUVmean=4.07 or SUVmean/liver=1.66 as a cut-off value. CONCLUSIONS: Our present study suggested that quantitative analysis of 18F-FDG-PET/CT imaging might be useful for selecting the biopsy site in IgG4-RD. The calculation of SUVmean, not of SUVmax, is important for evaluating IgG4-RD-related lesions in 18F-FDG PET/CT imaging.
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Fluordesoxiglucose F18 , Doença Relacionada a Imunoglobulina G4 , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos RadiofarmacêuticosRESUMO
OBJECTIVES: To determine prognostic factors for the Health Assessment Questionnaire-Disability Index (HAQ-DI) progression in patients with rheumatoid arthritis (RA) in clinical practice. METHODS: We evaluated 388 biological disease-modifying anti-rheumatic drug (bDMARD)-naïve Japanese patients with RA with moderate to high disease activity at study entry after being treated with conventional synthetic DMARDs. These patients were treated according to a treat-to-target (T2T) strategy for one year. The Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the HAQ-DI were assessed every three months. We also evaluated joint destruction using a modified total Sharp score at baseline and at one year. HAQ-DI progression was defined as the yearly progression of HAQ-DI >0.1. We performed a multiple logistic regression analysis to explore the factors predicting HAQ-DI progression at one year. RESULTS: HAQ-DI progression was observed in 18% of the patients. The multiple logistic regression analysis revealed the independent variables associated with HAQ-DI progression were: DAS28-ESR >5.1 at baseline (odds ratio [OR] 0.31, 95% con dence interval [CI] 0.13-0.74, p=0.0083); HAQ-DI score at baseline <0.5 (OR 2.27, 95% CI 1.22-4.26, p=0.0102); and achievement of low disease activity at 12 weeks (OR 0.42, 95% CI 0.21-0.82, p=0.0112). CONCLUSIONS: Our data suggest that maintaining clinical improvement according to T2T and initiating the treatment at an early stage are important for functional improvement after one year and that patients with low baseline HAQ scores have a higher risk of HAQ disability progression.
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Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Avaliação da Deficiência , Progressão da Doença , Humanos , Japão/epidemiologia , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
WHAT IS KNOWN AND OBJECTIVE: Tumour necrosis factor-α-blocking agents potentially cause vasculitis. However, no study has reported on the association between hypocomplementemic urticarial vasculitis (HUV) and certolizumab pegol (CZP) usage. CASE DESCRIPTION: We present the first case of HUV development during CZP treatment for rheumatoid arthritis. Hypocomplementemic urticarial vasculitis improved after CZP was discontinued and the dose of oral prednisolone was increased. WHAT IS NEW AND CONCLUSION: Clinicians should be aware about the potential development of HUV during CZP treatment, which is presumed to be safe considering its unique structural characteristics that differ from those of other tumour necrosis factor-α-blocking agents.
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Antirreumáticos/efeitos adversos , Certolizumab Pegol/efeitos adversos , Urticária/induzido quimicamente , Vasculite/induzido quimicamente , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Certolizumab Pegol/administração & dosagem , Feminino , Doenças da Deficiência Hereditária de Complemento/induzido quimicamente , Doenças da Deficiência Hereditária de Complemento/diagnóstico , Doenças da Deficiência Hereditária de Complemento/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Urticária/diagnóstico , Urticária/tratamento farmacológico , Vasculite/diagnóstico , Vasculite/tratamento farmacológicoRESUMO
A man in his 40s with a history of congenitally corrected transposition of the great arteries (CCTGA) and closure of ventricular septal defect was referred to our hospital with purpura and hematuria. Presence of purpura, renal damage, and pathological findings on skin biopsy led to the diagnosis of IgA vasculitis (IgAV). Oral prednisolone (PSL) was initiated. However, Streptococcus pseudoporcinus was isolated from blood cultures, and transthoracic echocardiogram revealed vegetation on the pulmonary valve. From these findings, the diagnosis of infective endocarditis (IE) was made. Although the patient's condition improved after PSL interruption and antibiotic administration, his purpura relapsed. PSL readministration improved symptoms, with no further relapse even after gradual PSL dose reduction. The present case raises awareness of the importance of recognizing the occurrence of IE in IgAV patients, especially in those with congenital heart disease. CCTGA should be acknowledged as a risk factor for IE in the right-sided heart.
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Transposição das Grandes Artérias Corrigida Congenitamente , Endocardite/complicações , Vasculite/imunologia , Adulto , Humanos , Imunoglobulina A , Masculino , Artéria PulmonarRESUMO
Objectives: To analyze the association among remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, diabetes mellitus (DM), and antidiabetic drugs.Methods: We retrospectively analyzed the clinical and serologic manifestations of patients who had RS3PE syndrome with and without pre-existing DM. Then we performed a subanalysis in which patients with pre-existing DM were classified into two groups according to whether they were or were not taking a dipeptidyl peptidase 4 inhibitor (DPP4i), an antidiabetic drug that was suggested to have an association with the pathogenesis of RS3PE syndrome.Results: Pre-existing DM was found in 13 (35.1%) of 37 patients with RS3PE syndrome. No significant differences in age, gender, physical manifestations, and laboratory findings were observed between the patients with DM and those without DM. DPP4i had been administered to 6 of 13 patients with RS3PE and pre-existing DM. We observed no significant differences in manifestations of RS3PE syndrome before treatment; however, one relapse occurred in a patient with poorly controlled DM who had been continuing DPP4i therapy.Conclusion: This study revealed no evidence suggesting an association among RS3PE syndrome, DM, and antidiabetic drugs. DPP4i would be safe for use by most of patients with RS3PE syndrome. However, elderly patients and patients with poorly controlled DM might require careful observation.
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Complicações do Diabetes/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Edema/epidemiologia , Hipoglicemiantes/efeitos adversos , Sinovite/epidemiologia , Idoso , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-IdadeRESUMO
Aim: To analyze the clinical course and prognosis in patients diagnosed with polymyalgia rheumatica (PMR) complicated by the presence of malignancies.Methods: We retrospectively screened the case files of 216 patients hospitalized in our department between 2011 and December 2016 for the results of a thorough physical examination and data on treatment for rheumatic diseases. We identified 53 patients with PMR according to Bird's criteria and 43 patients with 2012 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for PMR, then analyzed the clinical and serologic manifestations of PMR in patients with (n = 6) and without (n = 47 in Bird' criteria, n = 37 in 2012 EULAR/ACR criteria) malignancy.Result: No significant differences in age, gender, smoking, and serum markers were observed between PMR patients with and without malignancy, but there were statistically significant differences in tender joint counts and the presence of swollen joints and peripheral arthritis in both Bird's criteria and 2012 EULAR/ACR criteria.Conclusion: The presence of swollen joints and peripheral arthritis may be useful signs that indicate the coexistence of malignancies in patients with PMR.
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Artrite/diagnóstico , Articulações/patologia , Neoplasias/diagnóstico , Polimialgia Reumática/diagnóstico , Idoso , Artrite/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Polimialgia Reumática/complicações , PrognósticoRESUMO
Morphological change that includes diffuse effacement of podocyte foot processes is correlated with proteinuria in patients with lupus nephritis (LN). We collected the data of clinico-pathological parameters and assessed foot process width (FPW) as an index of podocyte effacement in 73 patients with LN who had undergone renal biopsy. The multivariate analysis revealed that female gender (OR: 5.288; 95%CI: 1.197-37.29; pâ¯=â¯.0267) and FPW (ORâ¯=â¯0.999, 95%CIâ¯=â¯0.997-0.999, pâ¯=â¯.0150) were significantly predictive of a complete renal response (CR) at 6â¯months, while lymphocyte counts (ORâ¯=â¯1.002; 95%CIâ¯=â¯1.001-1.003, pâ¯=â¯.0028) and FPW (ORâ¯=â¯0.998, 95%CIâ¯=â¯0.996-0.999, pâ¯=â¯.0027) were significantly predictive of CR at 12â¯months. The cut-off point determined by the Classification and Regression Trees algorithm showed that FPW <908.3â¯nm provides the best performance for predicting patients who achieve CR at 12â¯months. A smaller FPW appears to be a predictive factor for CR at 6 and 12â¯months after induction therapy.
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Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Podócitos/ultraestrutura , Adulto , Creatinina/urina , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Feminino , Humanos , Modelos Logísticos , Nefrite Lúpica/patologia , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Ácido Micofenólico/uso terapêutico , Prednisolona/uso terapêutico , Prognóstico , Proteinúria , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença , Tacrolimo/uso terapêuticoRESUMO
The cell-surface glycoprotein CD52 is widely expressed in lymphocytes. CD4+CD52hi T cells are functioning suppressor CD4+T cells. We investigated the role of the immune regulation of CD4+CD52 T cells in systemic lupus erythematosus (SLE). CD4+CD52lo T cells were increased in SLE patients, in positive correlation with SLEDAI, anti-ds-DNA antibody, and IgG concentration. Circulating follicular helper-like T cells (Tfh-like cells) were also increased in SLE, in positive correlation with CD4+CD52lo T cells. Chemokine receptor 8 (CCR8) expression in CD4+CD52lo T cells was increased. In vitro experiments using CD4 T cells of SLE patients showed that thymus and activation-regulated chemokine (TARC), a ligand of CCR8, contributed to the development of CD4+CD52hi T cells into CD4+CD52lo T cells. Our findings suggest that CD4+CD52lo T-cell upregulation is involved in the production of pathogens by autoantibodies, and TARC may contribute to the development of SLE through an aberrant induction of CD4+CD52lo T cells.
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Linfócitos T CD4-Positivos/imunologia , Antígeno CD52/imunologia , Quimiocina CCL17/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Imunoglobulina G/imunologia , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Receptores CCR8/imunologia , Índice de Gravidade de Doença , Regulação para Cima , Adulto JovemRESUMO
OBJECTIVES: To detect HTLV-I bZIP factor (HBZ), tax and relevant molecules in labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS). METHODS: The expressions of HBZ and tax in T cell lines and LSGs were analysed by in situ hybridization (ISH) or real time PCR. The expressions of forkhead box P3 (Foxp3) and p65 in immunohistochemistry were quantified. RESULTS: After specificity of ISH probes was determined in 5 T cell lines, in LSGs from an adult T-cell leukemia (ATL) patient and 3 HTLV-I-associated myelopathy (HAM)-SS patients, both HBZ and tax signals were detected in infiltrating mononuclear cells (MNCs) and ducts, and HBZ and tax were dominantly expressed in MNCs of ATL and HAM-SS, respectively. HBZ was dominantly observed in LSGs from 8 HTLV-I asymptomatic carrier (AC)-SS patients; faint expression of HBZ was observed in LSGs from 5 HTLV-I-seronegative SS patients. No cell adhesion molecule 1(CADM1) expressed in LSGs from the ATL patient. Although Foxp3 expression was observed in LSG MNCs of all of the SS patients, the ATL patient's expression was significantly greater than that of the AC-SS (p<0.01) and HTLV-I-seronegative SS (p<0.01) patients. The Foxp3 expression was similar in ATL and HAMSS, but significantly higher in HAM-SS than AC-SS (p<0.05). p65 was expressed in LSG MNC nuclei from all SS patients and co-expressed with Foxp3. The expressions of Foxp3 in ducts differed according to HTLV-I infection. CONCLUSIONS: These results suggest that HBZ-mediated Foxp3 expression is partly associated with the pathogenesis of HTLV-I-seropositive SS.
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Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Produtos do Gene tax/metabolismo , Proteínas dos Retroviridae/metabolismo , Glândulas Salivares/metabolismo , Síndrome de Sjogren/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Estudos de Casos e Controles , Fatores de Transcrição Forkhead/metabolismo , Produtos do Gene tax/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Células Jurkat , Reação em Cadeia da Polimerase em Tempo Real , Proteínas dos Retroviridae/genética , Glândulas Salivares/imunologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Fator de Transcrição RelA/metabolismoRESUMO
The pathogenesis of Sjögren's syndrome (SS) involves multiple factors including genetic background, cell death, and exocrine dysfunction. We here discuss apoptotic control in exocrine glands in SS by showing various pro- and anti-apoptotic pathways. Although the membrane-bound and soluble form of the Fas/Fas ligand system is a leading player with activation of the death domain and caspase 8/3 cleavage, the role of soluble Fas/FasL (including its polymorphism) in apoptosis is controversial. The tumor necrosis factor related apoptosis-inducing ligand (TRAIL)-mediated apoptosis of salivary gland epithelial cells (SGECs) involves a mitochondrial pathway that includes caspase 9 cleavage. The involvement of innate immunity cells such as toll-like receptors (TLRs) has been investigated; TLR2-4 and TLR7-9 are associated with the induction of inflammation in exocrine glands of SS patients. TLR3 has the potential to induce the apoptosis of SS patients' SGECs. Linkage of epidermal growth factor (EGF) was shown in exocrine glands in SS, and it inhibited the Fas/FasL system with the help of cell-survival factors. TLR3 has dual actions to cause inflammation as well as apoptosis, which are inhibited by EGF. In conclusion, apoptosis in exocrine glands of SS patients is tightly controlled by balance of pro-apoptotic signals and growth factor.
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Apoptose , Fator de Crescimento Epidérmico/imunologia , Glândulas Exócrinas/imunologia , Proteína Ligante Fas/imunologia , Síndrome de Sjogren/imunologia , Receptor fas/imunologia , Animais , Caspase 9/imunologia , Sobrevivência Celular , Glândulas Exócrinas/patologia , Humanos , Síndrome de Sjogren/patologia , Receptores Toll-Like/imunologiaAssuntos
Diabetes Mellitus , Inibidores da Dipeptidil Peptidase IV , Sinovite , Sedimentação Sanguínea , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Dipeptidil Peptidases e Tripeptidil Peptidases , Edema/complicações , Edema/tratamento farmacológico , Humanos , Hipoglicemiantes , Sinovite/complicações , Sinovite/tratamento farmacológicoRESUMO
OBJECTIVE: To examine whether magnetic resonance imaging (MRI) findings at baseline predict radiographic progression in early-stage rheumatoid arthritis (RA) patients who have achieved sustained good clinical response. METHODS: This is a sub-analysis from the one-year observational study of Nagasaki University Early Arthritis Cohort. Definition of 'good clinical response' was a decrement of disease activity score (DAS) 28 ⧠1.2 at three months with achievement of DAS28 remission through 6-12 months. Gd-enhanced MRI of both wrists and finger joints were examined at baseline and scored using rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Annual increment of Genant-modified Sharp score (GSS) > 0 was defined as 'radiographic progression'. Predictors of radiographic progression were determined by logistic regression analysis. RESULTS: Twenty-four subjects were selected in the present study. Each median RAMRIS synovitis, bone edema, bone erosion, and GSS at baseline were 6.5, 0.5, 0, and 0, respectively. Five patients developed radiographic progression at one year. Multivariate logistic regression analysis has shown that RAMRIS bone erosion at baseline is the only independent predictor of radiographic progression at one year (p = .032). CONCLUSIONS: Our data suggest that MRI bone erosion predicts poor radiographic outcome of early-stage RA even if it has been successfully treated.
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Artrite Reumatoide/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Articulações/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , RadiografiaRESUMO
INTRODUCTION: Neuropsychiatric systemic lupus erythematosus (NPSLE), a serious organ disorder with a variety of symptoms, has diverse therapeutic outcomes because of the variability of NPSLE manifestations. A comprehensive association study of NPSLE among clinical and immunopathogenic aspects and outcomes has not been conducted. METHODS: We analyzed the laboratory data, NPSLE symptoms, and clinical outcomes at 1yr post-treatment and the profiles of 27 cytokines, chemokines and growth factors in cerebrospinal fluid (CSF) samples using the Bio-Plex Human 27-plex panel from 28 NPSLE patients. Univariate and multivariable competing risks regression analyses were used to determine the predictive factors of clinical response. We also tried to predict the outcome of NPSLE by the 27 cytokines/chemokines/growth factors using a weighted-voting (WV) algorithm. RESULTS: Of the two males and 26 females (92.9%), 16 were non-responders at 1yr post-treatment; in the final model, the independent predictors of non-responders were longer disease durations of SLE (odds ratio [OR]: 1.490, 95% confidence interval [CI]: 1.143-2.461, p=0.0003) and patients with more than one NPSLE symptom types (OR: 15.14, 95% CI: 1.227-452.1, p=0.0334). The pretreatment CSF interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels were significantly higher in the non-responders (p=0.0207, p=0.0054, p=0.0242 and p=0.0077, respectively). We identified six "minimum predictive markers:" IL-10, TNF-α, IL-6, IFN-γ, IL-4 and IL-13 by a WV algorithm that showed the highest accuracy (70.83%) and highest Matthews correlation coefficient (54.23%). CONCLUSIONS: We have devised a numerical prediction scoring system that was able to separate the non-responders from responders. The patients with longer disease durations of SLE and those with more than one NPSLE symptom types had poorer outcomes. Our findings may indicate both the importance of making a diagnosis at an earlier phase for better therapeutic response and the usefulness of measuring multiple cytokines to predict NPSLE therapeutic outcomes.
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Citocinas/líquido cefalorraquidiano , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Adulto , Algoritmos , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate whether the Clinical Disease Activity Index (CDAI) at three months predicts a preferable CDAI outcome at one year in patients with active rheumatoid arthritis (RA) treated with tocilizumab (TCZ). METHODS: Seventy-eight RA patients in the Nagasaki Prefecture, Japan, whose disease activities at baseline were moderate to high as estimated by the CDAI and who had received 8 mg/kg of TCZ every four weeks, were consecutively enrolled in this study from April 2008 to March 2011. The association of the CDAI at three months with that at one year was examined by the Cochran-Armitage test. The variables at baseline and at three months that were predictive of remission or low disease activity (LDA) according to the CDAI at one year were assessed by logistic regression analysis. RESULTS: Most of the patients (40 out of 44: 91%), whose CDAI at three months showed remission or LDA continued to show remission or LDA at one year. Disease activity at three months significantly correlated with the frequency of LDA or remission at one year (p<0.0001). Logistic regression analysis revealed that only remission or LDA at three months as determined by the CDAI was predictive of remission or LDA at one year as determined by the CDAI (odds ratio 33.2, p<0.0001). CONCLUSIONS: A preferable clinical outcome as estimated by the CDAI at one year in active RA patients treated with TCZ is predicted by the CDAI at three months, suggesting that the treat-to-target strategy carried out using the CDAI can be used in clinical practice in these patients.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Avaliação da Deficiência , Feminino , Nível de Saúde , Indicadores Básicos de Saúde , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Indução de Remissão , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of this study was to clarify the molecular mechanisms elicited by toll-like receptor (TLR)3 in salivary gland cell death in patients with SS. METHODS: Expression of TLR3 and its downstream molecules was examined by immunohistochemical analysis, immunofluorescence, Western blot (WB), and antibody dot-blot array in labial salivary glands (LSGs), and cultured primary salivary gland epithelial cells (SGECs) obtained from patients with SS. We also investigated the difference of expression between ducts/alveoli of LSGs and cultured SGECs. RESULTS: Phosphorylated Fas-associated protein with death domain (p-FADD) or caspase-8 was not found in ducts or alveoli of LSGs from SS patients and controls. Weak expression of receptor-interacting serine/threonine-protein kinase 3 (RIPK3) was found in SS patients, whereas no staining was observed in LSGs of controls. In contrast to LSGs, stimulation of SGECs with polyinosinic:cytidylic acid (poly I:C) significantly induced the expression of RIPK3, p-FADD, and cleaved caspase-8 by immunofluorescence and RIPK3, p-FADD, and cleaved caspase-3 by WB. However, it was counteracted by epidermal growth factor (EGF). Co-localization of anti-apoptotic molecules hemeoxygenase-2, heat shock protein 27, and p-protein kinase B or p-Akt was induced in EGF-stimulated SGECs. CONCLUSIONS: We observed that poly I:C induced apoptosis of SGECs in vitro compared with a relatively low prevalence of apoptosis found in the ducts and alveoli of LSGs in vivo. Thus, we speculate that other counter-regulatory mechanisms, including those induced by EGF, might exist to protect against TLR3-mediated apoptosis of ductal and acinar epithelial cells in vivo.
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Apoptose/imunologia , Glândulas Salivares Menores/metabolismo , Síndrome de Sjogren/metabolismo , Receptor 3 Toll-Like/metabolismo , Adulto , Idoso , Linhagem Celular , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Proteína de Domínio de Morte Associada a Fas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Proteína Serina-Treonina Quinases de Interação com Receptores , Transdução de Sinais/imunologia , Síndrome de Sjogren/imunologiaRESUMO
OBJECTIVE: To investigate whether aquaporins (AQPs) are involved in salivary gland dysfunction in patients with neuromyelitis optica (NMO) complicated with Sjögren's syndrome (SS). METHODS: Eight primary SS (pSS) patients, four NMO spectrum disorder (NMOsd) patients complicated with SS (NMOsd-SS), and three control subjects were enrolled. Immunohistochemistry of labial salivary glands (LSGs) was performed to determine the expressions of AQP4, AQP5, and tumor necrosis factor-alpha (TNF-α). In vitro expression of AQP5 was examined by Western blotting in cultured primary salivary gland epithelial cells (SGECs). RESULTS: No expression of AQP4 was shown in all LSGs. AQP5 was clearly expressed in the all acini, but the predominant localization of AQP5 in the apical side was diminished in the patients with pSS or NMOsd-SS compared with the controls and tended to be even lower in NMOsd-SS than pSS. The abnormal localization of AQP5 was associated with poor saliva secretion. No difference was found in TNF-α expression in the LSGs between patients with pSS and NMOsd-SS. AQP5 expression of SGECs in vitro was not changed by TNF-α or interleukin-10. CONCLUSIONS: Our results suggest that AQP5 but not AQP4 contributes to salivary secretion in patients with SS including those with NMO complicated with SS.
Assuntos
Aquaporina 5/metabolismo , Neuromielite Óptica/metabolismo , Saliva/metabolismo , Glândulas Salivares Menores/metabolismo , Síndrome de Sjogren/metabolismo , Adulto , Idoso , Aquaporina 4/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Interleucina-10/farmacologia , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/complicações , Neuromielite Óptica/patologia , Glândulas Salivares Menores/efeitos dos fármacos , Glândulas Salivares Menores/patologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/patologia , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
OBJECTIVE: To evaluate the efficacy of switching the route from intravenous tocilizumab (TCZ) infusion (TCZ-IV) to subcutaneous TCZ injection (TCZ-SC) in a real-world setting through a comparison of the clinical response. METHODS: Fifty-eight rheumatoid arthritis (RA) patients, for whom TCZ-SC was initiated following TCZ-IV between June 2013 and August 2014, were consecutively enrolled. Disease activity score (DAS)28-ESR, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were examined at baseline and after switching from TCZ-IV to TCZ-SC for 3 months. We investigated whether body weight and body mass index (BMI) affected the efficacy of TCZ-SC. RESULTS: Most of the patients had achieved remission or low disease activity at baseline (77.6% examined by DAS28). Fifty-seven patients (98%) continued the TCZ-SC treatment, and the disease activity was well controlled after 3 months. ΔDAS28 tended to be worsened after switching to TCZ-SC in the high-body-weight groups (≥60 kg) as compared with the groups with body weight <60 kg, although no statistical significance was found. BMI did not affect the efficacy of TCZ-SC. CONCLUSIONS: Caution should be exercised in the high-body-weight subjects, but these data indicate that TCZ-SC maintains the favorable RA disease activity established using TCZ-IV.