RESUMO
Objectives: We investigated whether the positivity of anti-citrullinated peptide antibody (ACPA) is associated with cigarette-smoking status and human T-cell leukaemia virus type 1 (HTLV-1) infection in a general population in Nagasaki, Japan, which is an ageing and HTLV-1-endemic area.Method: Baseline data from community-dwelling people in the Nagasaki Islands Study (NaIS) were included in this cross-sectional analysis. ACPA and HTLV-1 were measured in 3887 subjects without a history of treatment for rheumatoid arthritis. A logistic regression analysis was performed to assess the relationship between ACPA positivity and candidates of correlation with ACPA, i.e. the cigarette-smoking status quantified by Brinkman's index (BI) and HTLV-1 positivity.Results: Fifty-one subjects (1.3%) showed ACPA positivity, and 650 subjects (16.6%) were HTLV-1 carriers. In an age- and gender-adjusted logistic regression analysis, the BI [odds ratio (OR) 1.09, 95% confidence interval (CI)1.02-1.14, p = 0.0031] and a BI value > 500 (OR 3.92, 95% CI 1.72-9.22, p = 0.0014) were each significantly associated with ACPA positivity. HTLV-1 positivity did not show any association with ACPA positivity.Conclusion: A significant effect of cigarette-smoking status on ACPA production was revealed, whereas HTLV-1 positivity was not associated with ACPA production in this general population.
Assuntos
Anticorpos Antiproteína Citrulinada/sangue , Fumar Cigarros/imunologia , Infecções por HTLV-I/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fumar Cigarros/sangue , Estudos Transversais , Feminino , Infecções por HTLV-I/sangue , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Vida Independente , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment.Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation.Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months.Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.
Assuntos
Abatacepte/administração & dosagem , Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/imunologia , Idoso , Anticorpos Antiproteína Citrulinada/imunologia , Antirreumáticos/administração & dosagem , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Japão , Masculino , Estudos Prospectivos , Resultado do Tratamento , UltrassonografiaAssuntos
Artrite Reumatoide/imunologia , Citocinas/imunologia , Febre Familiar do Mediterrâneo/imunologia , Adulto , Idoso , Sedimentação Sanguínea , Proteína C-Reativa/imunologia , Quimiocina CX3CL1/imunologia , Quimiocina CXCL10/imunologia , Feminino , Fator Estimulador de Colônias de Granulócitos/imunologia , Humanos , Inflamação , Interleucina-10/imunologia , Interleucina-17/imunologia , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
OBJECTIVES: Bone oedema is a pathological change in rheumatoid arthritis (RA) that is detectable by magnetic resonance imaging (MRI). Recent histological analyses revealed that a prominent feature of bone oedema is the replacement of adipose tissue with inflammatory cells. Here, we demonstrate the possible roles of mesenchymal stromal cells (MSCs) in bone oedema formation and the pathogenic potential of the cells in RA. METHODS: Adipogenesis of bone marrow-derived human MSCs was induced by a standard adipogenic induction medium in the presence or absence of cytokines. The cytokine productions from MSCs were screened by an antibody array system and confirmed by ELISA. The migration assay was performed to determine the locomotive abilities of undifferentiated MSCs or MSCs after adipogenesis. The expression of α smooth muscle actin (SMA) and F-actin was examined by immunostaining and phalloidin staining, respectively. RESULTS: TNF-α, interleukin (IL)-1ß, IL-6, and TGF-ß clearly inhibited the adipogenesis of MSCs. Production of IL-6 was markedly reduced, and IL-8 secretion was augmented in MSCs after adipogenesis. The mobility of MSCs after adipogenesis was clearly reduced in migration assays compared to that of undifferentiated MSCs. Consistent with these findings, SMA and F-actin expressions were clearly suppressed in MSCs committed to adipogenesis. CONCLUSIONS: Our data suggest that the inflammatory milieu promotes bone oedema by blocking adipogenesis of MSCs. In bone oedema, the enhanced IL-6 production and the increased mobility of MSCs may contribute to the progression of RA. Therefore, bone oedema may be an important target lesion in the treatment of RA.