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1.
Mod Rheumatol ; 33(1): 182-186, 2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-35134992

RESUMEN

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.


Asunto(s)
Diabetes Mellitus , Arteritis de Células Gigantes , Polimialgia Reumática , Humanos , Masculino , Femenino , Polimialgia Reumática/complicaciones , Polimialgia Reumática/epidemiología , Polimialgia Reumática/diagnóstico , Estudios Retrospectivos , Pueblos del Este de Asia , Arteritis de Células Gigantes/complicaciones , Diabetes Mellitus/epidemiología
2.
Rheumatology (Oxford) ; 60(5): 2333-2341, 2021 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-33166998

RESUMEN

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.


Asunto(s)
Glomerulonefritis Membranosa/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Quimioterapia de Inducción , Nefritis Lúpica/tratamiento farmacológico , Adulto , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Estudios Retrospectivos
3.
Clin Exp Rheumatol ; 39(6): 1338-1344, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33506750

RESUMEN

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.


Asunto(s)
Fluorodesoxiglucosa F18 , Enfermedad Relacionada con Inmunoglobulina G4 , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Radiofármacos
4.
Clin Exp Rheumatol ; 38(6): 1096-1101, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32896260

RESUMEN

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.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Evaluación de la Discapacidad , Progresión de la Enfermedad , Humanos , Japón/epidemiología , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
5.
J Clin Pharm Ther ; 45(5): 1179-1182, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31990069

RESUMEN

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.


Asunto(s)
Antirreumáticos/efectos adversos , Certolizumab Pegol/efectos adversos , Urticaria/inducido químicamente , Vasculitis/inducido químicamente , Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Certolizumab Pegol/administración & dosificación , Femenino , Enfermedades por Deficiencia de Complemento Hereditario/inducido químicamente , Enfermedades por Deficiencia de Complemento Hereditario/diagnóstico , Enfermedades por Deficiencia de Complemento Hereditario/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Prednisolona/administración & dosificación , Urticaria/diagnóstico , Urticaria/tratamiento farmacológico , Vasculitis/diagnóstico , Vasculitis/tratamiento farmacológico
6.
Int Heart J ; 61(2): 404-408, 2020 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-32173704

RESUMEN

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.


Asunto(s)
Transposición Congénitamente Corregida de las Grandes Arterias , Endocarditis/complicaciones , Vasculitis/inmunología , Adulto , Humanos , Inmunoglobulina A , Masculino , Arteria Pulmonar
7.
Mod Rheumatol ; 30(4): 703-707, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31500483

RESUMEN

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.


Asunto(s)
Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Edema/epidemiología , Hipoglucemiantes/efectos adversos , Sinovitis/epidemiología , Anciano , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad
8.
Mod Rheumatol ; 29(6): 1013-1016, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30334628

RESUMEN

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.


Asunto(s)
Artritis/diagnóstico , Articulaciones/patología , Neoplasias/diagnóstico , Polimialgia Reumática/diagnóstico , Anciano , Artritis/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Polimialgia Reumática/complicaciones , Pronóstico
9.
Clin Immunol ; 197: 161-168, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30296591

RESUMEN

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; p = .0267) and FPW (OR = 0.999, 95%CI = 0.997-0.999, p = .0150) were significantly predictive of a complete renal response (CR) at 6 months, while lymphocyte counts (OR = 1.002; 95%CI = 1.001-1.003, p = .0028) and FPW (OR = 0.998, 95%CI = 0.996-0.999, p = .0027) were significantly predictive of CR at 12 months. The cut-off point determined by the Classification and Regression Trees algorithm showed that FPW <908.3 nm provides the best performance for predicting patients who achieve CR at 12 months. A smaller FPW appears to be a predictive factor for CR at 6 and 12 months after induction therapy.


Asunto(s)
Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Podocitos/ultraestructura , Adulto , Creatinina/orina , Ciclofosfamida/uso terapéutico , Ciclosporina/uso terapéutico , Femenino , Humanos , Modelos Logísticos , Nefritis Lúpica/patología , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Análisis Multivariante , Ácido Micofenólico/uso terapéutico , Prednisolona/uso terapéutico , Pronóstico , Proteinuria , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tacrolimus/uso terapéutico
10.
Clin Immunol ; 187: 50-57, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29031579

RESUMEN

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.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Antígeno CD52/inmunología , Quimiocina CCL17/inmunología , Lupus Eritematoso Sistémico/inmunología , Adolescente , Adulto , Anticuerpos Antinucleares/inmunología , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Inmunoglobulina G/inmunología , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Receptores CCR8/inmunología , Índice de Severidad de la Enfermedad , Regulación hacia Arriba , Adulto Joven
11.
Clin Exp Rheumatol ; 36 Suppl 112(3): 51-60, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29600938

RESUMEN

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.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Productos del Gen tax/metabolismo , Proteínas de los Retroviridae/metabolismo , Glándulas Salivales/metabolismo , Síndrome de Sjögren/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Estudios de Casos y Controles , Factores de Transcripción Forkhead/metabolismo , Productos del Gen tax/genética , Humanos , Inmunohistoquímica , Hibridación in Situ , Células Jurkat , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas de los Retroviridae/genética , Glándulas Salivales/inmunología , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/genética , Síndrome de Sjögren/inmunología , Factor de Transcripción ReIA/metabolismo
12.
Int J Mol Sci ; 19(8)2018 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-30103522

RESUMEN

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.


Asunto(s)
Apoptosis , Factor de Crecimiento Epidérmico/inmunología , Glándulas Exocrinas/inmunología , Proteína Ligando Fas/inmunología , Síndrome de Sjögren/inmunología , Receptor fas/inmunología , Animales , Caspasa 9/inmunología , Supervivencia Celular , Glándulas Exocrinas/patología , Humanos , Síndrome de Sjögren/patología , Receptores Toll-Like/inmunología
14.
Mod Rheumatol ; 27(6): 961-966, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28269999

RESUMEN

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.


Asunto(s)
Artritis Reumatoide/diagnóstico por imagen , Huesos/diagnóstico por imagen , Imagen por Resonancia Magnética , Adulto , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Progresión de la Enfermedad , Femenino , Humanos , Articulaciones/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Radiografía
15.
Cytokine ; 79: 31-7, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26745468

RESUMEN

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.


Asunto(s)
Citocinas/líquido cefalorraquídeo , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Vasculitis por Lupus del Sistema Nervioso Central/tratamiento farmacológico , Adulto , Algoritmos , Biomarcadores/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
16.
Clin Exp Rheumatol ; 34(5): 808-812, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27384149

RESUMEN

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.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/diagnóstico , Evaluación de la Discapacidad , Femenino , Estado de Salud , Indicadores de Salud , Humanos , Japón , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Valor Predictivo de las Pruebas , Inducción de Remisión , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento
17.
Mod Rheumatol ; 26(1): 99-104, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-25926385

RESUMEN

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.


Asunto(s)
Apoptosis/inmunología , Glándulas Salivales Menores/metabolismo , Síndrome de Sjögren/metabolismo , Receptor Toll-Like 3/metabolismo , Adulto , Anciano , Línea Celular , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosforilación , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Transducción de Señal/inmunología , Síndrome de Sjögren/inmunología
18.
Mod Rheumatol ; 26(3): 384-90, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26375433

RESUMEN

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.


Asunto(s)
Acuaporina 5/metabolismo , Neuromielitis Óptica/metabolismo , Saliva/metabolismo , Glándulas Salivales Menores/metabolismo , Síndrome de Sjögren/metabolismo , Adulto , Anciano , Acuaporina 4/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Humanos , Inmunohistoquímica , Interleucina-10/farmacología , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/patología , Glándulas Salivales Menores/efectos de los fármacos , Glándulas Salivales Menores/patología , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/patología , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología
19.
Mod Rheumatol ; 26(6): 891-899, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27459020

RESUMEN

OBJECTIVE: To clarify the efficacy and safety of abatacept for secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). METHODS: The primary endpoint of this open-labeled, prospective, observational multicenter study for secondary SS with RA was the remission rate of Simplified Disease Activity Index (SDAI) at 52 weeks after initiation of abatacept. The secondary endpoints included Saxon's test and Schirmer's test. Adverse events and adherence rate during the study period were also analyzed. RESULTS: Thirty-six patients (all females) were enrolled in this study. The mean SDAI decreased significantly from 20.6 ± 11.2 (±SD) at baseline to 10.0 ± 10.5 at 52 weeks (p < 0.05). Patients with SDAI remission increased from 0 (0 week) to 12 patients (33.3%) at 52 weeks. Saliva volume assessed by Saxon's test increased significantly from 2136 ± 1809 (0 week) to 2397 ± 1878 (24 weeks) mg/2 min (n = 34, p < 0.05). Saliva volume increased significantly from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min in 11 patients with Greenspan grade 1 or 2 of labial salivary gland biopsy (p < 0.05), but no change was noted in 18 patients with Greenspan grade 3 or 4. Tear volume by Schirmer's test increased significantly from 4.2 ± 4.8 (0 week) to 6.4 ± 7.8 (24 weeks) mm/5 min (n = 30, p < 0.05). The adherence rate to abatacept was 80.6% (29/36) over the 52-week period. Twelve adverse events occurred in 10 of the 36 patients, and 7 of these events were infections. CONCLUSION: Abatacept seems to be effective for both RA and SS related manifestations.


Asunto(s)
Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Síndrome de Sjögren/tratamiento farmacológico , Abatacept/administración & dosificación , Abatacept/efectos adversos , Adulto , Anciano , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Artritis Reumatoide/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Sjögren/etiología
20.
Mod Rheumatol ; 26(3): 415-420, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26381884

RESUMEN

OBJECTIVES: The aim of this study is to identify variables at diagnosis to predict the subsequent relapse in patients with Takayasu arteritis (TA). METHODS: We retrospectively analyzed 33 patients with TA in our hospitals from April 2000 to July 2015. We collected baseline variables at diagnosis including clinical symptoms and laboratory data using medical records and investigated associations of these indices with subsequent relapses. RESULTS: The patients included two males and 31 females (94%). The median age at diagnosis was 39 years old, and the median follow-up duration was 90 months. Relapse was noted in 18 patients (55%). Only lower total cholesterol (Tcho) [median, 117 mg/dL (relapse) vs. 182 mg/dL (nonrelapse)] was preferentially distributed in the relapse group as compared with the non-relapse group. Multivariable logistic analysis showed that hypocholesterolemia (<150 mg/dL) at diagnosis was the only predictor of subsequent relapse (odds ratio: 5.43, 95% confidence interval: 1.13-30.19; p = 0.035). The nonrelapse survival rate was significantly lower in the group with a Tcho level <150 mg/dL by Kaplan-Meier estimate (p < 0.001). CONCLUSIONS: We found that hypocholesterolemia at diagnosis is a predictor of subsequent relapse in patients with TA.


Asunto(s)
Dislipidemias/complicaciones , Arteritis de Takayasu/complicaciones , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Arteritis de Takayasu/diagnóstico
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