RESUMEN
The complement system contributes to the pathogenesis of systemic lupus erythematosus (SLE). Mannose-binding lectin (MBL) is a key molecule of the lectin pathway of complement and seems to be related to the clinical manifestations of this disease. We evaluated the serum levels of MBL and its relationship with disease onset and clinical findings in SLE patients. Serum samples were analysed in 195 patients and 145 healthy controls from southern Brazil. Patients with high MBL levels (above 2000 ng/ml) showed a significant increase in the frequency of thrombocytopaenia ( p = 0.007; OR = 2.71; 95% CI = 1.32-5.55); and seizures ( p = 0.034; OR = 2.61; 95% CI = 1.07-6.37). A positive correlation between disease activity and MBL levels (>2000 ng/ml; p = 0.031, rho = 0.279) as well as of MBL concentration with accumulated organ damage ( p = 0.021; rho = 0.232) was observed. Our results suggest a role for MBL in the development of clinical manifestations such as thrombocytopaenia and seizures in SLE patients. These findings corroborate the participation of the lectin pathway of complement in the pathophysiologic mechanisms underlying clinical manifestations of SLE.
Asunto(s)
Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Lectina de Unión a Manosa/sangre , Convulsiones/sangre , Trombocitopenia/sangre , Adulto , Brasil , Estudios de Casos y Controles , Complemento C3/metabolismo , Complemento C4/metabolismo , Femenino , Humanos , Modelos Logísticos , Masculino , Lectina de Unión a Manosa/genética , Persona de Mediana Edad , Convulsiones/etiología , Índice de Severidad de la Enfermedad , Trombocitopenia/etiologíaRESUMEN
Extracellular vesicles released from pathogens may alter host cell functions. We previously demonstrated the involvement of host cell-derived microvesicles (MVs) during early interaction between Trypanosoma cruzi metacyclic trypomastigote (META) stage and THP-1 cells. Here, we aim to understand the contribution of different parasite stages and their extracellular vesicles in the interaction with host cells. First, we observed that infective host cell-derived trypomastigote (tissue culture-derived trypomastigote [TCT]), META, and noninfective epimastigote (EPI) stages were able to induce different levels of MV release from THP-1 cells; however, only META and TCT could increase host cell invasion. Fluorescence resonance energy transfer microscopy revealed that THP-1-derived MVs can fuse with parasite-derived MVs. Furthermore, MVs derived from the TCT-THP-1 interaction showed a higher fusogenic capacity than those from META- or EPI-THP-1 interaction. However, a higher presence of proteins from META (25%) than TCT (12%) or EPI (5%) was observed in MVs from parasite-THP-1 interaction, as determined by proteomics. Finally, sera from patients with chronic Chagas disease at the indeterminate or cardiac phase differentially recognized antigens in THP-1-derived MVs resulting only from interaction with infective stages. The understanding of intracellular trafficking and the effect of MVs modulating the immune system may provide important clues about Chagas disease pathophysiology.
Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Enfermedad de Chagas/parasitología , Monocitos/parasitología , Trypanosoma cruzi/fisiología , Animales , Antígenos de Protozoos/inmunología , Micropartículas Derivadas de Células/parasitología , Enfermedad de Chagas/inmunología , Enfermedad de Chagas/metabolismo , Chlorocebus aethiops , Interacciones Huésped-Parásitos , Humanos , Fusión de Membrana , Ratones Endogámicos BALB C , Monocitos/metabolismo , Proteoma/metabolismo , Células VeroRESUMEN
The activation of complement on the surface of Leishmania promastigotes appears to be an important factor for parasite infectivity in the mammalian host, allowing their attachment and the invasion of macrophages via complement receptors. Mannose-binding lectin (MBL) is a well-known complement activator and an efficient opsonine. We have investigated here whether serum and purified MBL bind to and promote lysis of live promastigotes of L. braziliensis; and evaluated the deposition of MBL, C1q, C4 and C3 on the parasite surface after interaction with non-immune normal human serum (NHS). We observed that both serum MBL and the purified MBL-MASP complex bind to the surface of L. braziliensis and that this binding occurred via the carbohydrate recognition domains of MBL. The binding of MBL, however, did not affect the lytic effect of complement on the parasites. The deposition of C1q, C4, C3 and parasite lysis was observed after incubation with NHS. EDTA but not EGTA abolished C3 deposition on the parasite surface, indicating the involvement of the alternative pathway in this process. Our results indicate that MBL binds to L. braziliensis and that this is mediated by a specific carbohydrate on the surface of parasites and provides evidence for antibody-independent mechanisms that complement activation on the parasite surface.
Asunto(s)
Activación de Complemento , Leishmania braziliensis/inmunología , Lectina de Unión a Manosa/inmunología , Lectina de Unión a Manosa/metabolismo , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Animales , Complemento C1q/metabolismo , Complemento C3/metabolismo , Complemento C4 , Citotoxicidad Inmunológica , Humanos , Inmunohistoquímica , Microscopía Confocal , Unión Proteica , Mapeo de Interacción de Proteínas , Estructura Terciaria de Proteína , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/metabolismoRESUMEN
The coexistence of celiac disease together with a range of autoimmune disorders has already been reported. The aims of this study were to perform a broad spectrum of autoantibodies in celiac patients (N = 56), their first-degree relatives (N = 118), and compare the data with healthy controls (N = 101) and patients with inflammatory bowel disease (N = 42; Crohn's disease, N = 18 and ulcerative colitis, N = 24). All serum samples were tested by indirect immunofluorescence to the anti-endomysium antibodies (EmA), anti-neutrophil cytoplasmic (ANCA), anti-smooth-muscle (SMA), anti-mitochondrial (AMA), anti-nuclear (ANA), anti-liver-kidney microsomal (LKM), anti-gastric parietal cells (GPCA), and anti-thyroid microsome (TMA). EmA were detected in 100% of celiac patients ingesting gluten and in 16.1% of the first-degree relatives, while ANCA were positive only in patients with ulcerative colitis (45.6%) and Crohn's disease (16.5%). Fourteen CD patients (25%) were positive for at least one of the other autoantibodies, with significant prevalence of TMA, ANA, and GPCA, while the relatives showed 17.8% of positivity, with an increased prevalence of ANA and TMA. These results emphasize the value of screening for different autoantibodies in celiac patients and their relatives and corroborate the need for evaluation and follow-up of these individuals.
Asunto(s)
Autoanticuerpos/sangre , Enfermedad Celíaca/inmunología , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Niño , Preescolar , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The aim of this study was to evaluate the complement activation in Brazilian patients with preeclampsia and to correlate it with the severity and clinical outcome of the disease. Plasma levels of C3d, SC5b-9, C3 and C4 were measured in 16 patients with preeclampsia and in 17 normotensive pregnant women. Ten patients developed severe and six mild disease. C3 and C4 levels were determined by turbidimetry using polyclonal specific antisera. C3d concentrations were evaluated through double-decker rocket immunoelectrophoresis and SC5b-9 was assayed by a double-antibody enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody against a neoantigen expressed in the formed complex. The mean levels of all variables were significantly higher in the preeclamptic group (before the delivery) when compared to the normal pregnancies. The complex SC5b-9 followed by C3d showed the most significant results for those comparisons (p < or = 0.00001). The levels of all parameters in the preeclampsia patients decreased significantly after the delivery. Again, the complex SC5b-9 and C3d showed the most significant results (p < or = 0.0004). None of the studied variables showed statistically significant differences regarding the severity of preeclampsia. These results confirm the activation of complement in preeclampsia, suggesting that this activation is related to the disease manifestation. Our findings further emphasize the involvement of complement activation in the pathological manifestations of preeclampsia.
Asunto(s)
Activación de Complemento , Preeclampsia/inmunología , Adolescente , Adulto , Brasil , Activación de Complemento/inmunología , Proteínas del Sistema Complemento/análisis , Femenino , Humanos , Embarazo , Índice de Severidad de la EnfermedadRESUMEN
This study investigated the autoantibody profile of 241 blood samples from 176 Kaingang and 65 Guarani Indians from three populations living on the Rio das Cobras and Ivaí reservations, in the state of Paraná, in southern Brazil. The presence of antimitochondrial, anti-smooth muscle, antinuclear, anti-parietal cell, and anti-liver-kidney microsome antibodies was determined by indirect immunofluorescence. These results were compared with samples from 100 healthy Caucasian individuals from the general population of the state. Total positivity was 9% for the indigenous population and 4% for the control population. The prevalence of anti-smooth muscle antibodies was significantly higher among the Guarani and Kaingang individuals from the Rio das Cobras reservation (P = 0.03). It is likely that the increased exposure that these indigenous Brazilians have to infectious diseases that were previously unknown to them comes from more contact with non-native populations, growing acculturation, and cultural practices that include scarification and tattooing. The presence of auto-antibodies in these Brazilian Indians may be related to mechanisms of molecular mimicry with viral or bacterial antigens.
Asunto(s)
Autoanticuerpos/análisis , Indígenas Sudamericanos , Adolescente , Adulto , Anticuerpos Antinucleares/análisis , Brasil , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This study investigated whether increased plasma levels of terminal complement complex (SC5b-9) or split products correlate with disease activity and clinical manifestations in Brazilian systemic lupus erythematosus (SLE) patients. Comparisons with conventional measurements of complement and other inflammatory markers were also performed. Plasma levels of SC5b-9, C3a desArg, C1rs-C1Inhibitor, C3b(Bb)P, C3, C4, erythrocyte sedimentation rate (ESR) and mucoproteins (MP) were measured in 41 patients with SLE of different disease activity: 10 patients with none, 15 patients with mild, and 16 patients with moderate or severe activity. All parameters, with the exception of C3 and C3b(Bb)P, showed a statistically significant correlation with disease activity. Plasma levels of SC5b-9, C3a desArg, C4, CH50, ESR and MP revealed significant differences between the groups of patients without activity and those with moderate or severe disease. Although none of the variables were able to discriminate between patients without and those with mild activity, SC5b-9, C3a desArg, C4, ESR and mucoproteins showed significant differences between the patients with mild and those with moderate or severe disease. Among all the variables, SC5b-9 levels showed the most significant results and correlated well with the severity of the disease (p < 0.0005). Our data suggest that elevated levels of complement activation products, particularly of SC5b-9 are more sensitive markers in assessing disease activity than conventional laboratory diagnosis. Modern complement diagnosis is therefore recommended for monitoring disease progress in SLE patients.