RESUMO
BACKGROUND: Anti-SS-A/Ro antibody (anti-SSA), the diagnostic marker of Sjögren's syndrome (SS), is often detected in systemic sclerosis (SSc). Some patients are diagnosed with SSc/SS overlap syndromes, while there are anti-SSA-positive SSc cases without SS. In this study, we investigated the clinical characteristics of SSc with anti-SSA and clarified the clinical impact of this antibody in SSc. METHODS: A retrospective chart review was conducted of 156 patients with SSc at Yokohama City University Hospital from 2018 to 2021. Clinical data, laboratory data, imaging, and autoantibody positivity status were collected and analysed to assess the association between these variables and anti-SSA using multivariable logistic regression analysis. RESULTS: This cohort included 18 men and 138 women with SSc (median age, 69.0 years). Thirty-nine patients had diffuse cutaneous SSc (dcSSc) (25%), and 117 patients had limited cutaneous SSc (75%). Forty-four patients were anti-SSA-positive. Among them, 24 fulfilled the SS criteria. Multivariable logistic regression revealed that anti-SSA was statistically associated with interstitial lung disease (ILD; odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.14-6.3; P = 0.024). Meanwhile, anti-SSA positivity tended to increase the development of digital ulcer (OR = 2.18; 95% CI, 0.99-4.82, P = 0.054). In the comparative analysis of the autoantibody single-positive and anti-SSA/SSc-specific autoantibody double-positive groups, the anti-SSA single-positive group showed a significantly increased risk of ILD (OR = 12.1; 95% CI, 2.13-140.57; P = 0.003). Furthermore, patients with SSc and anti-SSA indicated that anti-SSA-positive SSc without SS was strongly associated with dcSSc when compared to that in patients with SS (OR = 6.45; 95% CI, 1.23-32.60; P = 0.024). CONCLUSIONS: Anti-SSA positivity increases the risk of organ involvement, such as ILD, in patients with SSc. Additionally, the anti-SSA-positive SSc without SS population may have more severe skin fibrosis than others. Anti-SSA may be a potential marker of ILD and skin severity in SSc.
Assuntos
Anticorpos Antinucleares , Escleroderma Sistêmico , Humanos , Masculino , Feminino , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/sangue , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Anticorpos Antinucleares/imunologia , Anticorpos Antinucleares/sangue , Estudos de Coortes , Adulto , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/diagnóstico , Idoso de 80 Anos ou maisRESUMO
Enhanced circulating blood periostin levels positively correlate with disease severity inãpatients with systemic sclerosis (SSc). Monocytes/macrophages are predominantly associated with the pathogenesis of SSc, but the effect of periostin on immune cells, particularly monocytes and macrophages, still remains to be elucidated. We examined the effect of periostin on monocytes and monocyte-derived macrophages (MDM) in the pathogenesis of SSc. The modified Rodnan total skin thickness score in patients with dcSSc was positively correlated with the proportion of CD80-CD206+ M2 cells. The proportion of M2 macrophages was significantly reduced in rPn-stimulated MDMs of HCs compared to that of SSc patients. The mRNA expression of pro-fibrotic cytokines, chemokines, and ECM proteins was significantly upregulated in rPn-stimulated monocytes and MDMs as compared to that of control monocytes and MDMs. A similar trend was observed for protein expression in the respective MDMs. In addition, the ratio of migrated cells was significantly higher in rPn-stimulated as compared to control monocytes. These results suggest that periostin promotes inflammation and fibrosis in the pathogenesis of SSc by possible modulation of monocytes/macrophages.
Assuntos
Monócitos , Escleroderma Sistêmico , Humanos , Fibrose , Macrófagos/metabolismo , Monócitos/metabolismo , Fenótipo , Escleroderma Sistêmico/patologiaRESUMO
BACKGROUND: Monocytes and macrophages are implicated in inflammation and atherosclerosis, whereas monocytes are involved in psoriasis lesion formation. We previously reported a psoriatic inflammation-associated significant decrease in the membrane protein caveolin-1 (CAV-1) in psoriasis patient monocytes. However, the phenotype of circulating monocytes and their macrophage differentiation in psoriasis patients remain unclear. OBJECTIVE: We sought to clarify circulating monocyte and monocyte-derived macrophage (MDM) phenotypes in psoriasis patients with and without comorbidities. METHODS: Thirty-one patients with psoriasis vulgaris and 28 control subjects were included. Surface macrophage markers and inflammatory status were examined in circulating monocytes and MDMs from both groups. Expression of CD36, which mediates macrophage uptake of oxidized low-density lipoprotein (oxLDL), was evaluated in these cells. CAV-1-silenced monocytes were differentiated into macrophages to investigate the effects of CAV-1 downregulation on psoriatic inflammation and atherosclerosis. RESULTS: Macrophage surface markers were detectable in circulating monocytes. A significant M1 shift was detected in monocytes and MDMs in psoriasis patients, including those without cardiovascular disease risk factors, as compared to controls. MDMs of psoriasis patients had more CD36-expressing cells, which are associated with atherosclerosis risk. Additionally, CAV-1-silencing in monocytes increased the likelihood of M1-biased macrophage differentiation and increased pro-inflammatory cytokine production. CONCLUSIONS: Monocytes from psoriasis patients were more likely to differentiate into M1-dominant macrophages, correlating with inflammatory status and CAV-1 expression. These aberrant inflammatory monocytes not only contribute to psoriatic inflammation by producing psoriatic cytokines, but also have a phenotype that could increase atherosclerosis risk by uptake of oxLDL and formation of foam cells.
Assuntos
Aterosclerose , Psoríase , Caveolina 1/genética , Caveolina 1/metabolismo , Caveolina 1/farmacologia , Citocinas/metabolismo , Humanos , Inflamação/metabolismo , Lipoproteínas LDL/genética , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacologia , Monócitos/metabolismo , Fenótipo , Psoríase/patologiaRESUMO
Monocytes and macrophages may be involved in the pathogenesis of systemic sclerosis (SSc); however, the etiology and regulation of monocyte and macrophage function in SSc remain unknown. IRF8 is a transcriptional regulator that is essential for the differentiation and function of monocytes and macrophages and thus may be involved in the regulation of macrophage phenotypes in SSc fibrosis. In this study, we measured IRF8 levels in circulating monocytes of 26 patients with SSc (diffuse cutaneous SSc, n = 11; limited cutaneous SSc, n = 15) and 14 healthy controls. IRF8 levels were significantly suppressed in monocytes of patients with diffuse cutaneous SSc and correlated negatively with the modified Rodnan total skin thickness score. Next, we assessed expression levels of cell surface markers, cytokine profiles, and components of extracellular matrix in IRF8-silenced monocyte-derived macrophages. IRF8-silenced monocyte-derived macrophages displayed an M2 phenotype and significantly upregulated mRNA and protein levels of profibrotic factors and extracellular matrix components. Finally, we assessed skin fibrosis in myeloid cell-specific IRF8 conditional knockout (Irf8flox/flox; Lyz2Cre/+) mice and found upregulated mRNA levels of extracellular matrix components and increased bleomycin-induced skin fibrosis. In conclusion, altered IRF8 regulation in monocytes and macrophages may be involved in SSc pathogenesis.
Assuntos
Fatores Reguladores de Interferon/metabolismo , Escleroderma Sistêmico/imunologia , Pele/patologia , Idoso , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Biópsia , Estudos de Casos e Controles , Diferenciação Celular , Células Cultivadas , Regulação para Baixo , Feminino , Fibrose , Voluntários Saudáveis , Humanos , Fatores Reguladores de Interferon/análise , Fatores Reguladores de Interferon/genética , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Cultura Primária de Células , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/patologia , Pele/imunologiaAssuntos
Autoanticorpos/imunologia , Dermatomiosite/complicações , Dermatomiosite/patologia , Fatores de Transcrição/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/etnologia , Estudos de Casos e Controles , Dermatomiosite/sangue , Feminino , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Prevalência , Dermatopatias/epidemiologia , Fatores de Transcrição/genéticaRESUMO
Dermatomyositis (DM) is an autoimmune inflammatory disease characterized by skin eruptions and myositis. Anti-transcriptional intermediary factor 1-γ antibody (anti-TIF1-γ Ab) is one of the most frequently detected myositis-specific autoantibodies and adults positive for anti-TIF1-γ have markedly higher rates of malignancy. Our aim was to determine the clinical associations of anti-TIF1-γ levels in 31 Japanese adult DM patients positive for anti-TIF1-γ. We determined associations between the anti-TIF1-γ index and patient characteristics and disease severities. Sixteen patients with anti-TIF1-γ Ab had concomitant malignancies. A mild positive correlation was found between the levels of serum creatine phosphokinase at the first visit and anti-TIF1-γ levels. In contrast, there was no significant difference in the anti-TIF1-γ Ab index between patients with and without malignancy. Dysphagia tended to be observed in patients with malignancy. On sequential analysis, anti-TIF1-γ levels in patients without malignancy were lower or turned negative after treatment for DM. Ab titers tended to be sustained in patients with stage IV malignancies. Interestingly, a re-increase in the Ab titer was observed on recurrence of malignancy or increase in DM activity. Four patients were completely cured of their malignancies, and anti-TIF1-γ levels in three patients turned negative with the loss of DM activity. These data suggest that higher anti-TIF1-γ titers may not directly indicate the presence of malignancy. Nevertheless, longitudinal changes in the anti-TIF1-γ index in individual patients may partially reflect activities of both DM and malignancy.
Assuntos
Autoanticorpos/sangue , Dermatomiosite/complicações , Doenças Pulmonares Intersticiais/epidemiologia , Neoplasias/epidemiologia , Fatores de Transcrição/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Creatina Quinase/sangue , Dermatomiosite/sangue , Dermatomiosite/diagnóstico , Dermatomiosite/imunologia , Feminino , Humanos , Japão/epidemiologia , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/imunologia , Masculino , Análise de Mediação , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/imunologia , Índice de Gravidade de DoençaRESUMO
Hydroxychloroquine is recommended as the first-line systemic treatment for cutaneous lupus erythematosus (CLE) in Western countries, and it was approved in Japan in 2016. However, the efficacy of hydroxychloroquine in various cutaneous lupus erythematosus subtypes in Japanese patients has not been elucidated to date. Therefore, we investigated the efficacy of hydroxychloroquine for the treatment of cutaneous manifestations according to CLE subtypes in Japanese patients. We enrolled 35 patients (29 diagnosed with systemic lupus erythematosus and six with CLE) in this retrospective study. We analyzed the efficacy of hydroxychloroquine for the treatment of cutaneous manifestations according to cutaneous lupus erythematosus subtypes, time to the first skin improvement, as well as effects on laboratory data and reduction of concomitant immunosuppressive drug administration at 16 and 32 weeks of therapy. Complete improvement was observed at high rates for acute CLE (ACLE); however, partial or non-improvement rates were higher for chronic CLE (CCLE) at 16 weeks. Several patients with alopecia without scarring achieved complete improvement at 32 weeks. CCLE tended to take more time to improve than ACLE. Overall, hydroxychloroquine was highly effective for skin: 87% of patients had at least some beneficial response at 16 weeks. Nevertheless, there were wide variations in complete improvement rates and duration for improvement among CLE subtypes. Our findings suggest that a therapeutic approach considering the subtypes of CLE will improve its management.