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1.
Clin Exp Rheumatol ; 34(6 Suppl 102): S64-S71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27462914

RESUMO

OBJECTIVES: To evaluate the efficacy of tocilizumab (TCZ), a monoclonal antibody against the interleukin (IL)-6 receptor, for refractory adult-onset Still's disease (AOSD) in the Korean population. METHODS: This retrospective study included 22 Korean patients with refractory AOSD who were given TCZ at one of seven university hospital-based clinics for rheumatic disease. Patients were subdivided into groups according to disease course: monocyclic, systemic polycyclic, and chronic articular. Modified Pouchot scores, including laboratory and clinical findings, were analysed at 6 months and 12 months. RESULTS: TCZ was given at 4-8 mg/kg every 4-5 weeks (8 mg/kg every 4-5 weeks in 18 patients, 6 mg/kg every 4 weeks in 2, and 4 mg/kg every 4 weeks in 2) for 7.5 months (median, IQR: 4.0-12.3). A good response (measured as a decrease of >2 in the modified Pouchot score) was achieved in 50.0% of patients (11 of 22) at 6 months and in 64.3% (9 of 14) at 12 months. The dose of corticosteroid dose was reduced from 11.5 mg/day (median, IQR: 10.0-21.3) immediately before TCZ therapy to 7.5 mg/day (median, IQR: 5.0-10.0, p=0.002) at 6 months and finally to 6.3 mg/day (median, IQR: 5.0-7.5, p=0.002) at 12 months. Only one patient discontinued TCZ treatment due to facial swelling accompanied by high blood pressure. In all others, adverse events subsided with delayed TCZ therapy, and TCZ therapy was continued successfully without problems. CONCLUSIONS: TCZ was effective for treating Korean AOSD patients who were refractory to conventional therapy or other anti-cytokine biologics, showing a corticosteroid-sparing effect and an acceptable tolerance profile.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Doença de Still de Início Tardio/tratamento farmacológico , Corticosteroides/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/diagnóstico , Fatores de Tempo , Resultado do Tratamento
2.
Lung ; 194(1): 97-105, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26608346

RESUMO

INTRODUCTION: We aimed to evaluate the association between specific anti-cyclic citrullinated peptide antibody (ACCPA) and pulmonary abnormalities in rheumatoid arthritis (RA) subjects. METHODS: Computed tomography (CT) images of 83 subjects with RA were evaluated in a blind fashion. Enrolled subjects underwent autoantibody testing to determinate titer of ACCPA and rheumatoid factor, and pulmonary function testing. Visual CT assessment included lobar analysis for extent of semi-quantitative total interstitial lung disease score (ILDS) and each airway abnormality score (bronchiectasis, bronchial wall thickening, centrilobular nodules, and expiratory air trapping). Correlation tests, and simple and multiple regression analyses were performed to determine the relationship between the visual CT abnormalities, physiologic parameters, and autoantibody titers. RESULTS: ACCPA-positive subjects had a greater extent and higher prevalence of small airway abnormalities including centrilobular nodules and air trapping compared to ACCPA-negative subjects (all p < 0.05). Bronchiectasis and bronchial wall thickening correlated with the ratio of forced expiratory volume in 1 s and forced vital capacity (FVC) (r = -0.236 and r = -0.329, all p < 0.05), and ILDS correlated with FVC and the diffusing capacity of the lung for carbon monoxide (r = -0.218 and r = -0.366, all p < 0.05). Bronchial wall thickening and air trapping correlated with ACCPA titers (r = 0.235 and r = 0.264, all p < 0.05). Air trapping and bronchial wall thickening were significantly associated with ACCPA titers. CONCLUSION: In ACCPA (+) RA, visual CT assessment of large and small airways beyond RA-ILD, which is attributable to RA-related autoimmunity, can provide valuable information regarding airway abnormalities, regardless of the patients' physiologic airflow limitations.


Assuntos
Artrite Reumatoide/sangue , Autoanticorpos/sangue , Bronquiectasia/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Peptídeos Cíclicos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/complicações , Bronquiectasia/complicações , Bronquiectasia/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/complicações , Capacidade de Difusão Pulmonar , Fator Reumatoide/sangue , Método Simples-Cego , Tomografia por Raios X , Capacidade Vital , Adulto Jovem
3.
Lung ; 194(5): 745-53, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27372294

RESUMO

OBJECTIVE: Lung diseases (LD) are common extra-articular manifestations in rheumatoid arthritis (RA). However, little is known about factors associated with susceptibility to rheumatoid arthritis-related lung diseases (RA-LD). The aim of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) of PADI4 and HLA-DRB1 alleles were associated with RA-LD. METHODS: Blood samples and clinical data were collected from 116 consecutive RA patients who satisfied the 1987 American College of Rheumatology classification criteria. RA-LD was diagnosed using high-resolution computed tomography of the chest. All patients were genotyped for SNPs of PADI4 and HLA-DRB1 alleles and analyzed for full amino acid sequence of the HLA protein corresponding to a 4-digit HLA typing. Data were analyzed by independent t test (or Mann-Whitney test) for continuous variables, Chi-square test (or Fisher's exact test) and trend test for categorical variables, and logistic regression analysis. RESULTS: Ninety-four (81.0 %) RA patients had LD, of which eight (6.9 %) had interstitial lung disease (ILD) and 92 (79.3 %) had airway abnormalities in which 64 (55.2 %) showed bronchiectasis and 47 (40.5 %) revealed bronchial wall thickening. The recessive genotype of padi4_92 was susceptible to airway abnormalities (OR = 2.22, 95 % CI = 1.05-4.49, p = 0.034). Tryptophan at position 9 of HLA-DRB1 sequence was associated with the susceptibility to RA-ILD (OR = 22.89, 95 % CI = 1.20-432.56, p = 0.037). CONCLUSION: PADI4 polymorphisms and HLA-DRB1 alleles could attribute differently to the development of airway abnormalities and ILD, respectively, in RA.


Assuntos
Artrite Reumatoide/complicações , Predisposição Genética para Doença , Cadeias HLA-DRB1/genética , Doenças Pulmonares Intersticiais/genética , Desiminases de Arginina em Proteínas/genética , Anormalidades do Sistema Respiratório/genética , Adulto , Idoso , Brônquios/patologia , Bronquiectasia/etiologia , Feminino , Genótipo , Humanos , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteína-Arginina Desiminase do Tipo 4
4.
Clin Immunol ; 161(2): 157-62, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26385092

RESUMO

Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE.


Assuntos
Predisposição Genética para Doença/genética , Leptina/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Genótipo , Humanos
5.
Autoimmunity ; 50(8): 435-440, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28959900

RESUMO

To investigate the expression patterns of activation-induced cytidine deaminase (AID) variants in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and examine their clinical implications, we isolated PBMCs from healthy controls (HC, n = 33) and patients with AS (n = 62), and measured mRNA expression of AID variants and translesion synthesis (TLS) polymerases using quantitative real-time polymerase chain reaction. The proportion of patients with AS in whom AID splicing variant (sv) 2 was expressed was significantly higher than that of HC (p = .031). 80.7% of AS patients were treated with tumour necrosis factor inhibitor (TNFi). Significantly higher proportion of the TNFi-treated group expressed sv2 compared to the TNF-naïve group (p = .037). And we compared the level of AID variants expression between the TNFi-treated group and the TNF-naïve group. The expression levels of AID full-length (FL) and sv1 were significantly lower in the TNFi-treated group than the TNF-naïve group (FL: p = .002, sv1: p = .045). In addition, we investigated mRNA expression levels of translesion synthesis (TLS) polymerases in PBMCs from patients with AS and HC. The expression level of TLS pol ι was significantly lower in patients with AS than in HC (p = .007). In conclusion, AS patients expressed significantly higher levels of sv2 than HC. TNFi treatment restored the gene expression of the AID variants (FL, sv1, and sv2) in patients with AS. A clear understanding of the underlying cellular and molecular mechanisms will help to identify the pathogenesis of AS better and to develop novel therapeutic targets.


Assuntos
Processamento Alternativo , Citidina Desaminase/genética , Regulação da Expressão Gênica , Espondilite Anquilosante/genética , Adulto , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Razão de Chances , Proteína FUS de Ligação a RNA/genética , Espondilite Anquilosante/diagnóstico , Avaliação de Sintomas , Inibidores do Fator de Necrose Tumoral , Adulto Jovem
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