RESUMO
Systemic lupus erythematosus (SLE) patients are susceptible to the development of posterior reversible encephalopathy syndrome (PRES). The main theory concerning the physiopathology of PRES suggests that there is brain-blood barrier damage, which is associated with endothelial dysfunction, and characterized by vasogenic oedema. However, current evidence regarding its physiopathogenic mechanisms is quite scant. The aim of this study was to analyse the expression of different serum cytokines, as well as vascular endothelial growth factor (VEGF) and soluble CD40 ligand (sCD40L), in patients with PRES/systemic lupus erythematosus (SLE) and to compare them with levels in SLE patients without PRES and in healthy controls. We performed a transversal study in a tertiary care centre in México City. We included 32 subjects (healthy controls, n = 6; remission SLE, n = 6; active SLE, n = 6 and PRES/SLE patients, n = 14). PRES was defined as reversible neurological manifestations (seizures, visual abnormalities, acute confusional state), associated with compatible changes by magnetic resonance imaging (MRI). Serum samples were obtained during the first 36 h after the PRES episode and were analysed by cytometric bead array, Luminex multiplex assay or enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-6 and IL-10 levels were significantly higher in PRES/SLE patients (P = 0·013 and 0·025, respectively) when compared to the other groups. Furthermore, IL-6 and IL-10 levels displayed a positive correlation (r = 0·686, P = 0·007). There were no differences among groups regarding other cytokines, sCD40L or VEGF levels. A differential serum cytokine profile was found in PRES/SLE patients, with increased IL-6 and IL-10 levels. Our findings, which are similar to those described in other neurological manifestations of SLE, support the fact that PRES should be considered among the SLE-associated neuropsychiatric syndromes.
Assuntos
Citocinas/sangue , Lúpus Eritematoso Sistêmico/sangue , Síndrome da Leucoencefalopatia Posterior/sangue , Adulto , Ligante de CD40/sangue , Estudos de Casos e Controles , Citocinas/genética , Feminino , Humanos , Separação Imunomagnética , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lúpus Eritematoso Sistêmico/complicações , Imageamento por Ressonância Magnética , Síndrome da Leucoencefalopatia Posterior/complicações , Centros de Atenção Terciária , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
The presence of anti-Ro52/tripartite motif 21 (Trim21) autoantibodies has been associated with a distinctive clinical profile and has gained value as a prognostic marker in idiopathic inflammatory myopathies (IIM). The aim of the present work was to analyse Ro52/Trim21 expression in different subsets of peripheral blood mononuclear cells (PBMCs) of patients with IIM, as well as the ubiquitination profile and its association with proinflammatory cytokine production. We included 18 patients with recent-onset IIM and 18 age- and gender-matched healthy donors. PBMCs were isolated and different subsets (CD4+ , CD8+ , CD14+ ) were purified by magnetic selection. The expression of Ro52/Trim21 in different PBMC subsets of patients with IIM and healthy donors was analysed by Western blot. We assessed the presence of myositis-specific and associated autoantibodies by enzyme-linked immunosorbent assay (ELISA). Cytokine levels were measured by cytometric bead array. Patients with IIM showed decreased protein expression of Ro52/Trim21 in comparison to healthy controls in PBMC (0·97 ± 0·60 versus 1·84 ± 0·92, P = 0·016), CD4+ lymphocytes (0·79 ± 0·54 versus 2·41 ± 0·78, P = 0·017), and monocytes (0·87 ± 0·35 versus 1·89 ± 0·20, P < 0·001). There were no significant differences among IIM groups. Also, a lower K48-mediated ubiquitination profile was found, predominantly in CD4+ lymphocytes. Furthermore, after mitogenic stimulation, there was a higher synthesis of proinflammatory cytokines by T cells [interleukin (IL)-17A and tumour necrosis factor (TNF)-α] and monocytes [IL-6 and interferon (IFN)-α] from IIM patients compared with healthy controls. Our data suggest that patients with IIM, mainly DM, are characterized by a deficient expression of Ro52/TRIM21 in different PBMC subsets (CD4+ lymphocytes and monocytes), along with lower K48-mediated ubiquitination, which is associated with a proinflammatory cytokine response.
Assuntos
Citocinas/metabolismo , Expressão Gênica , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Miosite/etiologia , Miosite/metabolismo , Ribonucleoproteínas/deficiência , Adulto , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biomarcadores , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Miosite/diagnóstico , UbiquitinaçãoRESUMO
In order to detect the presence of Hypoderma lineatum stage I larvae within the esophagus of cattle slaughtered in Chihuahua, Chihuahua, Mexico, a total of five samplings were carried out between July and November 2000. In each instance, a random sample was taken from 10% of the animals slaughtered in a single work shift in each of the two slaughterhouses included in this study. The esophagus were cut longitudinally in order to carry out visual inspection and detect the presence of H. lineatum stage I larvae in the submucosa. The larvae were separated and counted. We identified the presence of H. lineatum stage I larvae in the esophagus for all sampling dates, nevertheless, within the last sampling only one esophagus had them. For all sampling dates the prevalence ranged between 11 and 33%; the latter corresponded to the sampling in October. A total of 287 esophagus was inspected of which 54 were positive with one or more larvae (19%); 233 larvae were obtained from these cases. The number of larvae recovered per sampling ranged from 46 to 74 between July and October, the highest number was found in September's sampling. The largest amount of stage I larvae per esophagus was 22 in the months of July and August. Larvae were always located in the submucosa of the esophagus and all were oriented longitudinally.