RESUMO
OBJECTIVES: To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment. METHODS: We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits. RESULTS: The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63). CONCLUSION: IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus.
Assuntos
Interleucina-17/sangue , Lúpus Eritematoso Sistêmico/sangue , Adolescente , Adulto , Idade de Início , Ansiedade/psicologia , Brasil , Estudos de Casos e Controles , Criança , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Família , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/psicologia , Masculino , Nefrite/sangue , Nefrite/complicações , Nefrite/imunologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis.
Assuntos
Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Íons/efeitos adversos , Metais/efeitos adversos , Nefrite/induzido quimicamente , Nefrite/imunologia , Animais , Anticorpos Antinucleares/imunologia , Modelos Animais de Doenças , Imunofluorescência/métodos , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/imunologia , Íons/imunologia , Rim/efeitos dos fármacos , Rim/imunologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/imunologia , Masculino , Metais/imunologia , Proteinúria/imunologia , Ratos , Ratos Long-EvansRESUMO
Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang-(1-7). Most available evidence supports a counter-regulatory role for Ang-(1-7) by opposing many actions of Ang II on AT1 receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang-(1-7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang-(1-7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang-(1-7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang-(1-7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases.
Assuntos
Angiotensina I/metabolismo , Rim/metabolismo , Modelos Biológicos , Nefrite/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Proteínas Proto-Oncogênicas/agonistas , Receptores Acoplados a Proteínas G/agonistas , Transdução de Sinais , Angiotensina I/uso terapêutico , Enzima de Conversão de Angiotensina 2 , Animais , Proliferação de Células/efeitos dos fármacos , Fibrose , Humanos , Rim/efeitos dos fármacos , Rim/imunologia , Rim/patologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/metabolismo , Leucócitos/patologia , Nefrite/imunologia , Nefrite/patologia , Nefrite/terapia , Fragmentos de Peptídeos/uso terapêutico , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/genética , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is a radical effector molecule of the innate immune system that can directly inhibit pathogen replication. In order to study subsequent iNOS kidney expression in experimental leptospirosis, Golden Syrian hamsters and C3H/HeJ mice were infected intraperitoneally with 10(2) or 10(7) virulent Leptospira interrogans serovar Copenhageni (LIC) strain Fiocruz L1-130. Results showed increased levels of iNOS mRNA and protein in kidneys of infected animals when compared to that in mock-infected animals. To get a deeper insight into the role of iNOS in experimental leptospirosis, both subject species were treated or not treated with 4-aminopyridine (4-AP, 0.3mg/kg), an iNOS inhibitor. Treatment of infected hamsters with 4-AP accelerated the mortality rate to 100% by one day and increased the mortality rate from 20 to 60% in mice at 14 days post-infection. In kidney tissues, 4-AP treatment increased the bacterial burden, as demonstrated through leptospiral DNA quantification by real-time PCR, and aggravated tubulointerstitial nephritis. In addition, iNOS inhibition reduced the specific humoral response against LIC when compared to that in untreated infected animals. According to these results, iNOS expression and the resulting NO have an important role in leptospirosis.
Assuntos
Leptospira interrogans/imunologia , Leptospirose/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Animais , Carga Bacteriana , Cricetinae , Modelos Animais de Doenças , Expressão Gênica , Perfilação da Expressão Gênica , Rim/imunologia , Rim/microbiologia , Rim/patologia , Mesocricetus , Camundongos , Camundongos Endogâmicos C3H , Nefrite/imunologia , Nefrite/microbiologia , Nefrite/patologia , Doenças dos Roedores/imunologia , Análise de Sobrevida , Regulação para CimaRESUMO
BACKGROUND: Anti-C1q antibodies have been described in systemic lupus erythematosus (SLE) as well as in other connective tissue diseases. They have been considered as a marker for disease activity and presence of nephritis. OBJECTIVE: The aim of this study was to determine the prevalence of anti-C1q antibodies in Brazilian lupus patients as well as analyze their association with different clinical and serologic parameters. METHODS: Sera from 81 SLE patients, based on the American College of Rheumatology (ACR) criteria, were collected from a lupus referral outpatient clinic in Salvador, Brazil. Antibodies to C1q were detected by an enzyme-linked immunoassay (ELISA) kit and antibodies to other cellular antigens identified by indirect immunofluorescence on HEp-2 cell substrate (ANA), or Crithidia luciliae (dsDNA), and to nucleosome by ELISA. A cutoff of 20 U was established for anti-C1q and anti nucleosome assays. RESULTS: Anti-C1q antibodies were detected in 39.5% (32/81) of SLE sera. The presence of anti-C1q antibodies was associated with proteinuria (P=0.028) but not with other laboratory or clinical features, such as anti nucleosome or anti-dsDNA antibodies, hematuria, urinary casts or renal failure, leukopenia, pericarditis, pleuritis, malar rash, seizures, and psychosis. There was a positive correlation between the titers of anti-C1q antibodies and the systemic lupuis erythematosus disease activity index (SLEDAI) score (r=0.370; P=0.001). CONCLUSION: This study in Brazilian SLE patients confirms previous findings of the association of anti-C1q antibodies with nephritis and disease activity.
Assuntos
Autoanticorpos/análise , Complemento C1q/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite/imunologia , Adulto , Brasil , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não ParamétricasRESUMO
The present study investigated the expression of the complement receptor type 1 (CR1) on the membrane of erythrocytes (CR1/E) of patients with systemic lupus erythematosus (SLE) by flow cytometry. We found a significant reduction in CR1/E numbers in SLE patients (n = 52), compared to controls (512 +/- 171 and 689 +/- 146, respectively, P = 0.0001). Reduction was more pronounced in active disease patients. The mean CR1/E number observed in patients with inactive disease was 546 +/- 163 CR1/E, while active SLE patients presented a mean of 385 +/- 133 CR1/E (P = 0.001). Patients with SLE with similar activity indexes tend to have similar CR1/E numbers, irrespective of disease severity. We also observed a trend to CR1/E reduction in severe nephritis patients. A small group of SLE patients with chronic renal failure and inactive disease showed CR1/E numbers nearly identical to controls (689 +/- 146 versus 686 +/- 123, respectively, P = 0.95). This was the only group of SLE patients with normal CR1/E numbers. These results confirm the CR1/E reduction in SLE patients as previously described, and also suggest that this reduction is related to disease activity and not to disease severity.
Assuntos
Eritrócitos/imunologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Receptores de Complemento/sangue , Adolescente , Adulto , Biomarcadores/sangue , População Negra , Doadores de Sangue , Brasil , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Pessoa de Meia-Idade , Nefrite/sangue , Nefrite/imunologia , Valores de Referência , Índice de Gravidade de Doença , População BrancaRESUMO
Treatment with cyclosporin A (CsA) improves proteinuria and reduces renal cellular infiltration in chronic serum sickness (CSS). We examined if these effects were associated with a reduced renal expression of CD54 and its ligands, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and MHC class II molecules. We studied two groups of rats in which CSS was induced by daily injections of ovalbumin (OVA): a group treated with CsA (OVA.CsA group, n = 11) and a group that received no treatment (OVA.CSS group, n = 11). An additional group of five rats (control group) received only phosphate buffer. Immunostaining techniques were used to follow CSS and to study the expression of CD54, CD18, CD11b/c, IFN-gamma, TNF-alpha and MHC class molecules. Proteinuria (mg/24 h) was reduced from 248.2 +/- 73.1 (OVA.CCS group) to 14.5 +/- 13.1 with CsA treatment (P < 0.0001). The renal expression of CD54 and its ligands (CD18 and CD11b/c) was reduced by 50% to 75%. Correspondingly, there was a 60% to 85% reduction in the number of infiltrating leucocytes. The number of cells expressing TNF-alpha, IFN-gamma and MHC II molecules was also reduced. CsA reduces expression of CD54 and its ligands. This effect is associated with a reduction of cellular infiltration, IFN-gamma, TNF-alpha-producing cells and with MHC II expression in the kidney. These findings suggest that expression of adhesion molecules plays a critical role in CSS and underline the importance of cellular immunity in this experimental model.
Assuntos
Ciclosporina/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Imunossupressores/uso terapêutico , Molécula 1 de Adesão Intercelular/biossíntese , Rim/metabolismo , Nefrite/tratamento farmacológico , Doença do Soro/tratamento farmacológico , Animais , Moléculas de Adesão Celular/biossíntese , Moléculas de Adesão Celular/genética , Quimiotaxia de Leucócito , Doença Crônica , Creatinina/sangue , Ciclosporina/farmacologia , Modelos Animais de Doenças , Antígenos de Histocompatibilidade/biossíntese , Antígenos de Histocompatibilidade/genética , Doenças do Complexo Imune/tratamento farmacológico , Doenças do Complexo Imune/etiologia , Imunização , Imunossupressores/farmacologia , Molécula 1 de Adesão Intercelular/genética , Interferon gama/biossíntese , Interferon gama/genética , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Masculino , Microscopia de Fluorescência , Nefrite/etiologia , Nefrite/imunologia , Ovalbumina/imunologia , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Ratos , Ratos Sprague-Dawley , Doença do Soro/imunologia , Doença do Soro/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
Mean platelet survival time in patients with acute poststreptococcal glomerulonephritis (APSGN) is reduced to 50-60% of the control values, and glomerular deposits of platelet factor 4 are found in these patients. In order to investigate further systemic platelet changes of pathogenic, clinical or prognostic significance, we measured the platelet serotonin (5-HT) content and the blood platelet counts during the 1st week of the disease in 27 patients with APSGN. Platelet 5-HT was significantly reduced in patients with APSGN as compared with patients with impetigo without glomerular involvement (785 +/- 54 vs. 1,329 +/- 94 ng 5-HT/10(9) platelets; p < 0.001). Similarly, the mean blood platelet count was reduced to 247 +/- 16 x 10(3) as compared with 303 +/- 14 x 10(3) in the controls (p < 0.05). Thirteen (48%) of these patients had individual values of platelet 5-HT lower than the 95% confidence interval calculated in the control group. No significant correlation was observed between the concentration of 5-HT and either the severity of the disease judged by the amount of urinary protein excretion and the serum creatinine value or the presence of circulating immune complexes. Significant correction of the platelet 5-HT content (to 1,180 +/- 111 ng/10(9) platelets; p < 0.01) and of the platelet counts (to 309 +/- 21 x 10(3); p < 0.01) were observed in the longitudinal study at least 2 weeks later. Platelet activation, with secretion of granular content and increased consumption, may explain these findings. Additionally, the reduced mean age of the circulating platelets could contribute to their decreased 5-HT levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Plaquetas/metabolismo , Nefrite/sangue , Contagem de Plaquetas , Serotonina/sangue , Infecções Estreptocócicas/complicações , Doença Aguda , Adolescente , Adulto , Complexo Antígeno-Anticorpo/sangue , Criança , Pré-Escolar , Creatinina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite/imunologia , Nefrite/microbiologia , Nefrite/urina , Proteinúria/complicaçõesRESUMO
Sera from 210 patients with APSGN, were tested for the presence of ANCA (IgG-isotype). Indirect immunofluorescence (IF) on ethanol fixed human PMNs was used, and for those positive sera, ELISA kits for PR3 (Proteinase 3) and MPO (Myeloperoxidase) was performed. ANCA were detected in 9% (18 out of 210 cases) in a predominantly diffuse cytoplasmic staining pattern in 14 cases (77%), and in a perinuclear pattern in the remaining 4 cases (22%). Anti-MPO was found in 4 cases (C-ANCA 3; P-ANCA 1) and anti-PR3 was always negative. The presence of ANCA was significantly associated with a more severe glomerular disease as assessed by the serum creatinine value and the crescents formation. Longitudinal studies performed in 11 cases have shown that raised levels of these autoantibodies may persist for at least six months, without relationship with disease activity. Further studies are required to dilucidate the specificity of these autoantibodies, and if its presence is either an epiphenomenon of the heterogeneous humoral immune response in streptococcal infection, or they play some pathogenic role in APSGN.
Assuntos
Autoanticorpos/sangue , Imunoglobulina G/sangue , Nefrite/imunologia , Nefrite/microbiologia , Infecções Estreptocócicas/imunologia , Adolescente , Adulto , Idoso , Anticorpos Anticitoplasma de Neutrófilos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Rim/patologia , Masculino , Pessoa de Meia-Idade , Mieloblastina , Nefrite/patologia , Peroxidase/imunologia , Serina Endopeptidases/imunologiaRESUMO
The reversal or inversal reactions, well studied in some research centers, is still imperfectly known, even contested or denied. This lack of knowledge has been one of the hindrances in the understanding of the mechanism of the hansenic neuritis. The evolution of the concepts about this question is studied, starting with Souza Lima and Souza Campos (1950), followed by Tajiri (1955), up to the present "I reaction" of Jopling, involving the "up grading" and "down grading" reactions. An interpretation of the reactional mechanism is given, with better possibilities for the understanding of clinical aspects and for therapy.