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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 619-621, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642246

RESUMO

OBJECTIVE: To explore the serum homocysteine (Hcy) level and its influence factors in systemic lupus erythematosus (SLE) patients. METHODS: 90 SLE patients were included in the study. According to the systemic lupus erythematosus disease activity index (SLEDAI) score, 41 patients were in active stage (> 9 scores), 49 patients were in inactive stage (≤9 scores), while 46 healthy individuals were selected as controls. Total cholesterol (TC), triacylglyceride (TG), serum creatinine (Ser), C-reactive protein (CRP), serum cystatin (cystin c, CysC) and Hcy level were measured. Analysis on the relationship between Hcy level and SLEDAI score, as well as serum indicators was conducted. RESULTS: The levels of Hcy, TG, TC, CRP and CysC in SLE patients were higher than healthy controls (P < 0.05), and the serum level in active SLE patients was higher than inactive SLE patients (P < 0.05). There was no significant difference in Ser level among the active SLE patients, inactive SLE patients and healthy controls (P>0.05). There was a positive correlation between Hcy level and SLEDAI score (r=0.698 3, P < 0.01), as well as CysC (r=0.597 5, P < 0.01). There was no significant correlation between Hcy level and CRP, TC, TG and Ser levels (P>0.05). CONCLUSIONS: The Hcy level in SLE patients was higher than healthy controls. The level of Hcy was positively correlated with the degree of disease activity. The Hcy level and SLEDAI score can be used as indicators to evaluate the activity of SLE.


Assuntos
Homocisteína/sangue , Lúpus Eritematoso Sistêmico/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Colesterol/sangue , Creatinina/sangue , Cistatina C/sangue , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Triglicerídeos/sangue
2.
Autoimmun Rev ; 18(11): 102392, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520805

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease where chronic inflammation and tissue or organ damage is observed. Due to various suspected causes, inadequate levels of vitamin D (a steroid hormone with immunomodulatory effects) has been reported in patients with SLE, however, contradictory. AIMS: The aim of this systematic review and meta-analysis was to evaluate the serum levels of vitamin D in patients with SLE in compared to healthy controls. METHODS: PubMed, SCOPUS, ScienceDirect and Google Scholar electronic databases were searched systematically without restricting the languages and year (up to March 2, 2019) and studies were selected based on the inclusion criteria. Mean difference (MD) along with 95% confidence intervals (CI) were used and the analyses were carried out by using a random-effects model. Different subgroup and sensitivity analyses were conducted. Study quality was assessed by the modified Newcastle-Ottawa Scale (NOS) and publication bias was evaluated by a contour-enhanced funnel plot, Begg's and Egger's tests. RESULTS: We included 34 case-control studies (2265 SLE patients and 1846 healthy controls) based on the inclusion criteria. Serum levels of vitamin D was detected significantly lower in the SLE patients than that in the healthy controls (MD: -10.44, 95% CI: -13.85 to -7.03; p < .00001). SLE patients from Asia (MD: -13.75, 95% CI: -21.45 to -6.05; p = .0005), South America (MD: -3.16, 95% CI: -4.62 to -1.70; p < .0001) and Africa (MD: -16.15, 95% CI: -23.73 to -8.56; p < .0001); patients residing below 37° latitude (MD: -11.75, 95% CI: -15.79 to -7.70; p < .00001); serum vitamin D during summer season (MD: -7.89, 95% CI: -11.70 to -4.09; p < .0001), patients without vitamin D supplementation (MD: -15.57, 95% CI: -19.99 to -11.14; p < .00001) or on medications like hydroxychloroquine, corticosteroids or immunosuppressants without vitamin D supplementation (MD: -16.46, 95% CI: -23.86 to -9.05; p < .0001) are in higher risk in presenting inadequate serum levels of vitamin D. The results remained statistically significant from different sensitivity analyses which represented the robustness of this meta-analysis. According to the NOS, 91.2% of the studies were considered as of high methodological quality (low risk of bias). No significant publication bias was detected from contour-enhanced and trim and fill funnel plots or Begg's test. CONCLUSION: Inadequate levels of serum vitamin D is significantly high in patients with SLE compared to healthy subjects, therefore, vitamin D supplementation with regular monitoring should be considered as part of their health management plans.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Vitamina D/sangue , Vitaminas/sangue , Estudos de Casos e Controles , Humanos
3.
Med. clín (Ed. impr.) ; 153(6): 225-231, sept. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-184027

RESUMO

Fundamento y objetivo: Analizar la asociación entre concentraciones de interferón-1alpha (INF1alpha), interleucina 10 (IL-10) y BLyS con la actividad clínica en el lupus eritematoso sistémico (LES). Pacientes y métodos: Estudio observacional transversal de 142 pacientes con LES y 34 controles sanos mediante analítica de sangre y orina y revisión de la historia clínica. La concentración sérica de citocinas se determinó mediante métodos colorimétricos. El análisis bioestadístico se realizó con R (3.3.2). Resultados: El 69% de pacientes mostraron al menos una citocina aumentada. Las tres citocinas están más elevadas en pacientes que en controles (p<0,001, p=0,005 y p=0,043), siendo INF1alpha el más frecuente. Los pacientes fueron categorizados según las concentraciones de las tres citocinas. Encontramos una asociación significativa entre concentraciones elevadas de IL-10/INF1alpha y una mayor actividad clínica según SELENA-SLEDAI (p<0,0001) y, en menor medida, con concentraciones aumentadas de INF1alpha/IL-10/BLyS. Concentraciones elevadas de IL-10/INF1alpha e INF1alpha/IL-10/BLyS se relacionaron con un mayor consumo de C3-C4 (p<0,001 y p=0,001) y títulos elevados de anti-dsDNA (p=0,001 y p=0,002). Concentraciones elevadas de INF1alpha/BLyS se relacionaron con títulos más altos de anti-dsDNA (p=0,004) y positividad ENA (p<0,001). Concentraciones altas de INF1alpha/IL-10/BLyS se relacionaron con la positividad de ANA (p<0,001) y anticuerpos antifosfolípidos (p=0,004). Conclusiones: INF1alpha, IL-10 y BLyS están más elevados en pacientes con LES que en controles sanos. El aumento de IL-10, asociado o no a aumento de BLyS y/o INF1alpha, es la citocina que mejor se ajusta a la actividad clínica del LES medida con métodos clásicos


Background and objective: to analyse the association between interferon-1alpha (INF1alpha), interleukin-10 (IL-10) and BLyS concentrations and clinical activity in systemic lupus erythematosus (SLE). Patients and methods: A cross-sectional, observational study of 142 SLE patients and 34 healthy controls was performed, through a complete blood and urine test and review of their medical history. Serum concentration of INF1alpha, IL-10 and BLyS was determined by colorimetric methods. A biostatistical analysis was performed with R (3.3.2.). Results: 69% of our SLE patients showed at least one cytokine increased. INF1alpha, IL-10 and BLyS are higher in SLE patients than in healthy controls (P<.001, P=.005 and P=.043, respectively), being INF1alpha the most frequent. Patients were categorised according to low or high concentrations of the three cytokines. We found a significant association between increased IL-10/INF1alpha concentrations and a higher clinical activity measured by SELENA-SLEDAI (P<.0001) and, to a lesser extent, an association with increased INF1alpha/IL-10/BLyS concentrations. Elevated levels of IL-10/INF1alpha and INF1alpha/IL-10/BLyS related to increased C3-C4 consumption (P<.001 and P=.001 respectively) and anti-dsDNA titres (P=.001 and P=.002 respectively). Elevated INF1alpha/BLyS related to higher anti-dsDNA titres (P=.004) and ENA positivity (P<.001). Increased levels of INF1alpha/IL-10/BLyS related to positivity of ANAs (P<.001) and APL (P=.004). Conclusions: INF1alpha, IL-10 and BLyS are higher in SLE patients than in healthy controls. Increased IL-10 levels, regardless of whether or not there were also increased levels of BLyS and/or INF1alpha, was the cytokine that best fit with clinical activity in SLE measured with classic methods


Assuntos
Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/sangue , Interferon Tipo I/sangue , Interleucina-10/sangue , Linfócitos B/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Estudos Transversais , Lúpus Eritematoso Sistêmico/urina , Colorimetria/métodos , Bioestatística , Anticorpos Antifosfolipídeos , Inquéritos e Questionários , Ensaio de Imunoadsorção Enzimática , Citocinas/sangue , Citocinas/urina
4.
Medicine (Baltimore) ; 98(33): e16798, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415387

RESUMO

To explore the values of C-reactive protein (CRP) and procalcitonin (PCT) in identifying infection and disease activity in systemic lupus erythematosus (SLE) patients.Patients with SLE and infection from April 2015 to January 2018 were included in this study. We compared the clinical characteristics and biomarkers between different groups and calculated the receiver operating characteristic curve, sensitivity, and specificity of the corresponding biomarkers. Logistic regression analysis was performed on the variables exhibiting significant differences in univariate analysis.A total of 177 SLE patients were retrospectively analyzed. The patients were divided into noninfected-inactive group, noninfected-active group, infected-inactive group, and infected-active group. CRP level of infected-inactive group was significantly higher than noninfected-inactive group (P < .05), but not significantly in infected-active group than noninfected-active group (P > .05). Multivariate analysis showed that CRP (>24.0 mg/L) was the only independent risk factor for SLE infection (odds ratio, OR = 2.896, P = .032). PCT level of infected-active group was significantly higher than infected-inactive group (P < .05), but not significantly in noninfected-active group than noninfected-inactive group (P > .05). SLE active group had shorter disease course, lower infection rate, higher PCT level, and lower platelet count (PLT). Multivariate logistic analysis showed that PCT (>0.048 ng/mL) and PLT (<150 × 10/L) were independent risk factors for SLE activity (OR = 3.498 and 4.391, P = .011 and 0.009), and disease course (>96 months) was independent protective factor (OR = 0.169, P < .001). The area under the curve of the logistic model was significantly larger than any single variable (all P < .05).CRP is the only effective marker for diagnosing infection in SLE patients. Moreover, PCT helps predict SLE activity.


Assuntos
Infecções Bacterianas/diagnóstico , Proteína C-Reativa/análise , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/microbiologia , Pró-Calcitonina/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
5.
Egypt J Immunol ; 26(1): 31-42, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332994

RESUMO

About 40-50% of all patients with systemic lupus erythematosus (SLE) patients are associated with significant morbidity and a poor prognosis. The transforming growth factor ß-1(TGF-ß1) is a member of cytokines families which has emerged as an important player in the pathogenesis of autoimmune diseases, including SLE. In this study we aimed to evaluate TGF-ß1 as a noninvasive diagnostic test for early diagnosis of LN and to assess the correlations between TGFß-1 and clinic-pathologic characteristics as well as disease activity of SLE. This case-control study included 188 patients with SLE, stratified into two subgroups LN group and Non-LN group. We assessed diseases activity by SLE disease activity index and measured TGEß-1 by using ELISA. Our results showed that LN patients had significant lower values of serum TGF-ß1 compared with non-LN patients (P < 0.001). Moreover, there were significant differences between LN histopathological classes. The lowest levels values of serum TGFß1 was in Class V. There were significant negative correlations between levels of TGF-ß1 and SLEDAI, fever, arthritis, proteinuria, hematuria, serum creatinine, thrombocytopenia, lymphopenia, ESR, ANA, pus cell and cellular cast's, all (P < 0.01). In lupus nephritis patients, TGF-ß1 levels were positively correlated with eGFR, C3 and C4 (P < 0.001). Linear regression analysis revealed that, eGFR, CRP, thrombocytopenia, and serum creatinine were independently correlated with TGF-ß1 among lupus nephritis patients (P < 0.001). According to Receiver Operating Characteristic analysis, the sensitivity and specificity of TGF-ß1 were 91% and 65.5%, respectively in the diagnosis of LN among SLE patients. As LN group had significantly lower values of serum TGFß1 and the values further decreased with more damage of kidney tissues and progression of SLE activity. We conclude that serum TGF- ß1 could be a valuable non-invasive marker for assessment of LN activity and organ damage.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Nefrite Lúpica/sangue , Fator de Crescimento Transformador beta1/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Humanos
6.
Egypt J Immunol ; 26(1): 101-112, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31333000

RESUMO

Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting all organ systems due to alterations of both innate and adaptive immune systems. Given the importance of several factors that may be incriminated in deregulation of immune system in SLE, we aimed to study MTNR1ß gene polymorphisms rs10830963 C/G, serum levels of melatonin and pro-inflammatory cytokines; TNF-α, IL-6, and IL-1ß in SLE patients and the correlation of these parameters to SLE disease activity and damage index at time of study. Subjects were subdivided into 2 groups: group I: 40 SLE patients attending Alexandria main university hospital and outpatient clinic, and group II: 40 control cases of apparently healthy individuals matched for age and sex. For all cases, MTNR1ß gene polymorphism rs10830963 was analyzed by quantitative RT-PCR, serum levels of melatonin, TNF-α, IL-6 and IL-1ß were detected by ELISA. Activity index (SLEDAI) and damage index (SLEDDI) were assessed in SLE patients. MTNR1ß gene polymorphism rs10830963 genotype in SLE patients showed that 50% had GG, 35% CG and 15% CC. The control group had significantly lower ratios, 5% had GG, 15% CG and 80% CC (P < 0.001). Serum melatonin level was decreased in SLE patients (P < 0.001). Serum levels of TNF-α, IL-6, and IL-1ß were increased in SLE patients compared to controls (P < 0.001, P < 0.001, P < 0.001 respectively). There was no correlation between serum melatonin level, TNF-α, IL-6, and IL-1ß with SLEDAI or SLEDDI. In conclusion, MTNR1ß gene polymorphism rs10830963 G allele may contribute in SLE pathogenesis. Inflammatory cytokines; TNF-α, IL-6, IL-1ß may have role in SLE disease manifestations. Targeting immunoregulators as melatonin and proinflammatory cytokines in SLE treatment strategy can be a promising way to SLE cure.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Melatonina/sangue , Polimorfismo Genético , Receptor MT2 de Melatonina/genética , Estudos de Casos e Controles , Egito , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Lúpus Eritematoso Sistêmico/sangue , Fator de Necrose Tumoral alfa/sangue
7.
Nat Commun ; 10(1): 2201, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101814

RESUMO

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Proteínas de Membrana/genética , Quinases da Família src/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Animais , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Núcleo Celular/imunologia , Núcleo Celular/metabolismo , Criança , Modelos Animais de Doenças , Feminino , Frequência do Gene , Células HEK293 , Voluntários Saudáveis , Humanos , Fatores Reguladores de Interferon/imunologia , Fatores Reguladores de Interferon/metabolismo , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação de Sentido Incorreto , Sequenciamento Completo do Exoma , Quinases da Família src/metabolismo
8.
Lupus ; 28(6): 713-721, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31046570

RESUMO

BACKGROUND: Current non-invasive methods of assessing disease activity in systemic lupus erythematosus (SLE) are of limited sensitivity and specificity. Testing includes acute phase markers, autoantibodies and complement levels. Although measurements of dsDNA antibodies and complement C3/C4 levels are routine, they remain of limited value. Improved blood and urine markers may help in early detection of flare, distinction between flare and chronic damage, and monitoring response to therapy. METHODS: A total of 87 patients with SLE were tested for the following cytokines in serum and urine: monocyte chemoattractant protein 1 (MCP-1), regulated upon activation, normal T cell expressed and secreted (RANTES), soluble tumour necrosis factor receptor 1 (sTNF-R1), interferon-inducible protein 10 (IP-10), monocyte inhibitory protein 1α (MIP-1α) and vascular endothelial growth factor (VEGF). Patients attending the Lupus Unit at St Thomas' Hospital, London, UK were divided into active lupus nephritis (LN), inactive LN and non-renal SLE groups based on their renal pathology and SLE disease activity index (SLEDAI). Cytokine testing was performed using the FIDIS multiplex bead assay. RESULTS: The mean level of serum sTNF-R1 was higher in the active LN group compared with both inactive LN and non-renal SLE groups ( p < 0.001). For urine measurements there were significant differences between active LN and non-renal SLE for VEGF ( p = 0.016), after statistical correction for multiple testing. Both urinary and serum sTNF-R1 and IP-10 levels correlated with SLEDAI scores ( p < 0.001), while serum VEGF correlated weakly with SLEDAI ( p = 0.025). The optimum combination for differentiating active from inactive LN patients was serum VEGF, sTNF-R1, MCP-1 and glomerular filtration rate plus urinary sTNF-R1 and protein-creatinine ratio. CONCLUSION: These results indicate that for active LN, sTNF-R1 could be a useful serum cytokine marker, with potential for VEGF in the urine. This study has confirmed the ability of the multiplex bead technique to detect cytokines in a good analytical range, including very low and high levels, in both serum and urine. Combining serum and urine markers provided additional sensitivity in distinguishing active from inactive LN.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Fator A de Crescimento do Endotélio Vascular/urina , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Quimiocina CCL2/sangue , Quimiocina CCL2/urina , Quimiocina CCL3/sangue , Quimiocina CCL3/urina , Quimiocina CCL5/sangue , Quimiocina CCL5/urina , Quimiocina CXCL10/sangue , Quimiocina CXCL10/urina , Estudos Transversais , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Modelos Logísticos , Londres , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/urina , Nefrite Lúpica/sangue , Nefrite Lúpica/urina , Masculino , Pessoa de Meia-Idade , Receptores Tipo I de Fatores de Necrose Tumoral/urina , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/sangue
9.
Clin Exp Rheumatol ; 37(5): 852-854, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31140395

RESUMO

OBJECTIVES: Fatigue remains a debilitating feature of systemic lupus erythematosus (SLE). Although in some cases this may be the result of intercurrent fibromyalgia, mood disorder or untreated metabolic syndrome, in many cases the cause is unclear. The aim of this study was to investigate the relationship between fatigue and red cell distribution width (RDW), a measure of variability in erythrocyte size and volume. METHODS: A total of 225 patients were recruited from three clinics in England and Australia. Patients completed the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score or 12-item Short Form survey (SF-12) to measure fatigue, which was compared with RDW and haemoglobin. In a subgroup of 72 patients, markers of disease activity were also assessed for correlation with fatigue using univariate and multivariate analysis with fatigue as the dependent variable. RESULTS: In all three groups, significant correlations between fatigue and RDW were observed (p<0.001; p=0.02; p<0.001 respectively) and this was preserved in multivariate analysis. There was no correlation between fatigue and haemoglobin in two groups (with the correlation between RDW and fatigue remaining significant in non-anaemic patients in the third group). In subgroup analysis, fatigue was not associated with any measures of disease activity. CONCLUSIONS: We report a reproducible, statistically significant association between RDW and fatigue levels in a diverse population of patients with SLE. The findings of this study raise the possibility of a potential novel biological basis for fatigue in those in whom there is a lack of an alternate explanation.


Assuntos
Anemia , Índices de Eritrócitos , Lúpus Eritematoso Sistêmico , Anemia/sangue , Austrália , Inglaterra , Fadiga , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/terapia , Índice de Gravidade de Doença
10.
Arch Immunol Ther Exp (Warsz) ; 67(3): 161-169, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30944972

RESUMO

The contribution of innate immune cells, including natural killer (NK) and natural killer T (NKT) cells, in systemic lupus erythematosus (SLE) is still unclear. Herein, we examined the frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells in patients with juvenile SLE and their potential relations to SLE-related clinical and laboratory parameters. The study included 35 SLE children and 20 apparently healthy controls. After baseline clinical and lab work, SLE Disease Activity Index (SLEDAI-2K) and Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI) scores were assessed. The frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells was examined using flow cytometry. SLE patients showed significantly lower frequency of NK cells and NKT cells and higher frequency of CD56bright NK cells compared to controls. Disease activity, urea, and creatinine correlated negatively with NK, but positively with CD56bright NK cells. NK and NKT cells exhibited inverse correlation with the renal biopsy activity index; however, CD56bright NK cells showed direct correlations with both activity and chronicity indices. Regarding Ped-SDI, renal, neuropsychiatry disorders, and growth failure correlated inversely with NK but directly with CD56bright NK cells. NKT cell inversely correlated with renal damage and delayed puberty. In conclusion, low frequency of NK and NKT and expansion of CD56bright NK cells are marked in juvenile SLE, particularly with activity. These changes have direct effect on renal impairment and growth failure, reflecting their potential influence on disease progression.


Assuntos
Antígeno CD56/metabolismo , Células Matadoras Naturais/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Células T Matadoras Naturais/imunologia , Adolescente , Antígeno CD56/imunologia , Separação Celular/métodos , Criança , Estudos Transversais , Progressão da Doença , Feminino , Citometria de Fluxo/métodos , Humanos , Imunidade Inata , Células Matadoras Naturais/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Masculino , Células T Matadoras Naturais/metabolismo , Índice de Gravidade de Doença
11.
Medicine (Baltimore) ; 98(14): e15030, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946340

RESUMO

BACKGROUND: Dyslipidemia is a common disorder in systemic lupus erythematosus (SLE) patients. It is still inconclusive whether antimalarial drugs could affect the serum lipids in SLE patients, therefore we conducted a systematic review and meta-analysis of available data to address this issue. METHODS: We comprehensively searched the databases of PubMed, EMBASE and Cochrane Library from date of inception to Sep 2018 for both randomized controlled trials (RCTs) and observational studies. Review Manager 5.3 software was used for analysis. We performed meta-analysis using random-effects model and weighted the mean difference (WMD) and its 95% confidence interval (CI). The Q test was used to assess the presence of heterogeneity and the I index was used to quantify the extent of heterogeneity. RESULTS: In total, 8 studies met our selection criteria including 2 RCTs, 2 cohort studies, and 4 case-control studies. There were 717 patients (336 patients in CQ (chloroquine) or HCQ (hydroxychloroquine) group, and 381 patients in control group (SLE patients without the therapy of AM)). Compared with the control group, TC, TG, LDL-C, VLDL-C were associated with a significant decrease, respectively (WMD = -21.40 mg/dL, 95% CI -27.62 to -15.18, P < .00001), (WMD = -29.07 mg/dL, 95% CI -45.28 to -12.86, P = .0004), (WMD = -16.25 mg/dL, 95% CI -28.82 to -3.68, P = .01), (WMD = -6.41 mg/dL, 95% CI -12.39 to 0.44, P = .04), however the change of HDL-C did not reach statistically significance (WMD = 4.42 mg/dL, 95% CI -1.21 to 10.06, P = .12). CONCLUSIONS: CQ or HCQ can infect the serum lipids in SLE patients. However, these results should be interpreted with cautions since lacking sufficient RCTs.


Assuntos
Antimaláricos/farmacologia , Lipídeos/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Cloroquina/farmacologia , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/etiologia , Feminino , Humanos , Hidroxicloroquina/farmacologia , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Horm Mol Biol Clin Investig ; 38(3)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943171

RESUMO

Background The importance of vitamin D (VD) in systemic lupus erythematosus (SLE) is being increasingly appreciated, with studies suggesting a relationship between VD deficiency and SLE onset/disease activity. We investigated VD status in SLE patients and its associations with disease activity in a geographical region of India receiving low solar ultraviolet-B (UV-B) index. Materials and methods We enrolled 109 SLE patients along with 109 healthy controls belonging to same ethnicity and localities. Demographic and clinico-laboratory information were recorded. VD status was assessed by estimating serum 25-hydroxyvitamin D (25-OH-D) concentrations (deficient: <20 ng/mL, insufficient: 21-29 ng/mL, and sufficient/normal: ≥30 ng/mL) using an enzyme-linked fluorescent assay (ELFA). The SLE Disease Activity Index (SLEDAI) scoring system was used to evaluate disease activity. The association between VD status and disease activity was assessed by univariate and multivariate approaches. Results Hypovitaminosis D was prevalent in 90.83% SLE patients [vs. 77.98% healthy controls; chi-squared (χ2) = 10.125, df = 2, p < 0.01]. SLEDAI scores and 25-OH-D values were inversely associated, which extended in a two-way manner as revealed by multiple logistic regression models. SLE patients with VD deficiency were more likely to have high/very high disease activity [adjusted odds ratio (OR) = 3.5, 95% confidence intervals (CI): 1.4-8.9]. Conversely, patients with high SLEDAI scores (>10) also had greater risks of being VD deficient (adjusted OR = 3.9, 95% CI: 1.5-10.8). Conclusion VD deficiency is widespread in SLE. The relationship appears to be bidirectional, with VD status associated both as determinant and outcome of disease activity in SLE.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Humanos , Índia , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Prevalência , Deficiência de Vitamina D/sangue
13.
Braz J Med Biol Res ; 52(4): e8131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30994732

RESUMO

The leading cause of death in systemic lupus erythematosus (SLE) patients is infection. The objective of this study was to evaluate the distribution of lymphocyte subsets in untreated SLE patients with infections. This was a cross-sectional study. Data from January 2017 to May 2018 were collected. Flow cytometry was used to measure the peripheral lymphocyte subsets including CD3+T cells, CD4+T cells, CD8+T cells, CD19+B cells, CD3-CD16+CD56NK cells, and CD3+CD16+CD56NKT cells in 25 healthy controls and 52 treatment-naive SLE patients, among whom 13 were complicated with infections. Association between the lymphocyte subsets and infections was further analyzed. SLE patients with infections (n=13) showed a significantly higher incidence rate of fever (84.6 vs 28.2%) and serositis (84.6 vs 23.1%), increased level of erythrocyte sedimentation rate (60.5±30.1 vs 37.4±27.1 mm/h), serum C-reactive protein (CRP) (102.7±94.9 vs 9.4±14.9 mg/L), procalcitonin (PCT) (1.07±0.08 vs 0.16±0.13 µg/L), and lower blood hemoglobin (Hb) (93.0±20.5 vs 110.4±16.0 g/L) level compared with non-infection patients (n=39) (all P<0.05). In comparison with non-infectious SLE patients (387.9±261.6/µL), CD4+T cells count decreased significantly in infectious SLE patients (217.8±150.4/µL) (P<0.05), and it was negatively correlated with infection-related indicators including PCT (r=-0.573, P=0.041) and CRP (r=-0.596, P=0.032) levels. Our findings suggested that abnormalities of peripheral lymphocyte subsets were related to the immune disorder of lupus itself, regardless of immunosuppressive treatment. Monitoring lymphocyte subsets, especially CD4+T cells, may be helpful for identifying the presence of infection in SLE patients.


Assuntos
/sangue , Lúpus Eritematoso Sistêmico/sangue , Subpopulações de Linfócitos , Adulto , Proteína C-Reativa/análise , Estudos de Casos e Controles , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Valores de Referência , Fatores de Risco , Estatísticas não Paramétricas , Adulto Jovem
14.
Mediators Inflamm ; 2019: 8450947, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31007604

RESUMO

Accumulating evidence indicates a critical role for T cells and relevant cytokines in the pathogenesis of systemic lupus erythematosus (SLE). However, the specific contribution of T cells together with the related circulating cytokines in disease pathogenesis and organ involvement is still not clear. In the current study, we investigated relevant molecule expressions and cytokine levels in blood samples from 49 SLE patients and 22 healthy control subjects. The expression of HLA-DR and costimulatory molecules on T cells was evaluated by flow cytometry. Concentrations of serum C-reactive protein, erythrocyte sedimentation rate, anti-double-stranded DNA (anti-dsDNA) antibody, total lgG, complement 3, and complement 4 were measured. Serum cytokines and chemokines were measured by a cytometric bead array assay. Elevated frequencies of HLA-DR+ T cells and ICOS+ T cells were observed in SLE patients with positive anti-dsDNA antibodies compared with those in healthy controls (P < 0.001). The expression of HLA-DR+ T cells was positively correlated with SLEDAI (r = 0.15, P < 0.01). Furthermore, levels of serum IL-6, MCP-1, TNFRI, IL-10, IL-12, and CCL20 were higher in SLE patients compared with healthy controls. In addition, patients with hematologic manifestations displayed elevated frequencies of HLA-DR+ T cells and ICOS+ T cells. Patients with renal manifestations had a decreased frequency of TIGIT+ T cells. These results suggested a dysregulated T cell activity and cytokine expression profiles in SLE subjects. We also developed a chemokine and cytokine profiling strategy to predict the activity of SLE, which has clinical implication for better monitoring the flares and remission during the course of SLE and for assessing therapeutic interventions.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Adulto , Idoso , Proteína C-Reativa/metabolismo , Quimiocina CCL17/sangue , Quimiocina CCL20/sangue , Complemento C3/metabolismo , Complemento C4/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina G/sangue , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Molecules ; 24(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31027344

RESUMO

The objective of this study was to identify novel acetylation (Ac) modifications of the C1-inhibitor (C1-INH) and explain the association of the levels of autoantibodies against acetylated C1-INH peptides with the risk of developing systemic lupus erythematosus (SLE). Ac modifications of the C1-INH were identified and validated through in-gel digestion, nano-liquid chromatography-tandem mass spectrometry, immunoprecipitation, and Western blotting by using serum protein samples obtained from patients with SLE and age-matched healthy controls (HCs). In addition, the levels of serum C1-INH, Ac-protein adducts, and autoantibodies against unmodified and acetylated C1-INH peptides were measured. C1-INH levels in patients with SLE were significantly lower than those in HCs by 1.53-fold (p = 0.0008); however, Ac-protein adduct concentrations in patients with SLE were significantly higher than those in HCs by 1.35-fold (p = 0.0009). Moreover, immunoglobulin M (IgM) anti-C1-INH367-385 Ac and IgA anti-C1-INH367-385 Ac levels in patients with SLE were significantly lower than those in HCs. The low levels of IgM anti-C1-INH367-385 (odds ratio [OR] = 4.725, p < 0.001), IgM anti-C1-INH367-385 Ac (OR = 4.089, p = 0.001), and IgA anti-C1-INH367-385 Ac (OR = 5.566, p < 0.001) indicated increased risks for the development of SLE compared with HCs.


Assuntos
Proteína Inibidora do Complemento C1/imunologia , Imunoglobulina A/imunologia , Imunoglobulina M/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Peptídeos/imunologia , Acetilação , Sequência de Aminoácidos , Autoanticorpos/imunologia , Autoantígenos/imunologia , Proteína Inibidora do Complemento C1/química , Proteína Inibidora do Complemento C1/metabolismo , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Peso Molecular , Peptídeos/química , Ligação Proteica/imunologia , Curva ROC , Taiwan
16.
Lupus ; 28(6): 748-754, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31023128

RESUMO

OBJECTIVE: This study aimed to assess IL-24 levels and their association with clinical manifestations in patients with systemic lupus erythematosus (SLE). METHODS: There were 75 patients with SLE and 58 healthy controls recruited in this study. Serum levels of IL-24 were measured by enzyme-linked immunosorbent assays, and mRNA levels of IL-24 were tested by quantitative real-time polymerase chain reaction . The area under the curve of the receiver operating characteristic (ROC) curve was used for diagnostic ability of the inflammatory cytokine. RESULTS: Serum IL-24 levels were significantly higher in SLE patients than that in healthy controls. SLE patients with nephritis had higher IL-24 levels than those without nephritis. Active SLE patients showed higher expression of IL-24 as compared to less active disease patients. The mRNA levels of IL-24 were much higher in SLE patients. Correlation analysis showed significant correlation between serum IL-24 levels and SLE disease activity index. In addition, ROC analysis may suggest good ability of serum IL-24 in differentiating SLE. CONCLUSION: The inflammatory cytokine correlated with SLE disease activity, and may be involved in this disease pathogenesis.


Assuntos
Interleucinas/sangue , Lúpus Eritematoso Sistêmico/sangue , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Predisposição Genética para Doença , Humanos , Interleucinas/genética , Lúpus Eritematoso Sistêmico/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença
17.
Chem Biol Interact ; 306: 110-116, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30991045

RESUMO

MicroRNAs (miRNAs) have been implicated in both biological and pathological processes in patients with systemic lupus erythematosus (SLE). Previous studies have demonstrated dysregulated expression of miR-199-3p, interleukin (IL)-10, and poly (ADP-ribose) polymerase-1 (PARP-1) in SLE. However, the underlying mechanisms of these aberrations have not been fully elucidated. In this study, we investigated the mechanism through which miR-199-3p dysregulation contributed to the pathogenesis of SLE. Altered gene expression was assessed by ChIP analysis. We then silenced the expression of candidate genes using siRNA for functional analysis; mRNA expression, protein levels, and protein expression were determined by qRT-PCR, ELISA, and western blotting, respectively. According to ChIP and qRT-PCR results, miR-199-3p was up-regulated in SLE patients. Moreover, IL-10 was found to be highly expressed in SLE patients by ELISA. Further, PARP1 was significantly down-regulated in SLE patients based on western blotting. Our results also indicated that miR-199-3p inhibits PARP1 expression by activating the ERK1/2 pathway, thereby increasing IL-10 expression. Significantly up-regulated miR-199-3p was inversely related to PARP-1 expression and positively correlated with IL-10 levels in SLE. As miR-199-3p was shown to target PARP-1 to activate the ERK1/2 pathway and promote IL-10 production, restoring physiological miR-199-3p levels could represent a potential therapeutic strategy for SLE treatment.


Assuntos
Interleucina-10/biossíntese , Lúpus Eritematoso Sistêmico/metabolismo , MicroRNAs/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Adulto , Feminino , Células HEK293 , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Mediators Inflamm ; 2019: 2473164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944545

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.


Assuntos
Linfócitos B/metabolismo , Linfócitos B/patologia , Plaquetas/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Adulto , Ligante de CD40/sangue , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade
19.
Lupus ; 28(4): 565-568, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30862250

RESUMO

Organizing pneumonia is an inflammatory lung entity that presents with a huge variety of clinical, radiological and pathological patterns. Organizing pneumonia can be idiopathic or secondary to other diseases. Corticosteroid therapy is usually the first-line treatment showing clinical improvement in most cases. This report presents the case of a 56-year-old woman with systemic lupus erythematosus who was diagnosed with an organizing pneumonia and showed a poor response to steroid and azathioprine treatment. We considered the use of belimumab, which resulted in excellent clinical and radiological outcomes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Bronquiolite Obliterante/tratamento farmacológico , Bronquiolite Obliterante/etiologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Anticorpos Antinucleares/sangue , Anticorpos Monoclonais Humanizados/administração & dosagem , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Bronquiolite Obliterante/sangue , Progressão da Doença , Tolerância a Medicamentos , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Leucocitose/sangue , Pulmão/diagnóstico por imagem , Pulmão/patologia , Lúpus Eritematoso Sistêmico/sangue , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Testes de Função Respiratória , Tomógrafos Computadorizados , Resultado do Tratamento
20.
Lupus ; 28(4): 520-528, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30871426

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are possible biomarkers for many diseases, but the knowledge of circRNAs in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) remains limited. This study aimed to assess the expression of circRNAs in PBMCs from patients with SLE and healthy individuals by RNA sequencing (RNA-seq). METHODS: In total, 128 circRNAs were significantly differentially expressed including 39 upregulated and 89 downregulated circRNAs in four new-onset SLE patients compared with three healthy controls. After verification of the four candidate circRNAs in 49 patients with SLE and 37 controls using quantitative real-time polymerase chain reaction (qRT-PCR) assays, a previously undescribed circRNA with potential translation activity, circPTPN22, was selected to confirm its clinical significance. RESULTS: Bioinformatics analysis demonstrated that the parent gene of circPTPN22 was protein tyrosine phosphatase non-receptor type 22 (PTPN22), a potent regulator of T cell activation. The downregulation of circPTPN22 in patients with SLE was strongly negatively correlated with their Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. circRNA-miRNA-mRNA co-expression network analysis indicated a correlation between circPTPN22 and the miRNAs and mRNAs related to immunological regulation including the development of SLE. Patients with higher SLEDAI scores had lower circPTPN22 expression levels, and long-term hormone treatment significantly increased circPTPN22 levels. Receiver operating characteristic curve analysis indicated that circPTPN22 has good diagnostic value for SLE. CONCLUSION: Our data demonstrated the aberrant expression of circRNAs in patients with SLE compared with healthy controls; circPTPN22 might function as a diagnostic and disease severity indicator in SLE.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , RNA/sangue , Adulto , Biomarcadores/sangue , China , Biologia Computacional , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Hospitais Universitários , Humanos , Leucócitos Mononucleares/imunologia , Lúpus Eritematoso Sistêmico/sangue , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA/genética , RNA Mensageiro/genética , Curva ROC , Análise de Sequência de RNA , Transcrição Genética , Regulação para Cima , Adulto Jovem
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