Assuntos
Aterosclerose/prevenção & controle , Autoimunidade/imunologia , Linfócitos T CD4-Positivos , Lipoproteínas HDL , Lúpus Eritematoso Sistêmico , Fator de Crescimento Transformador beta1/sangue , Aterosclerose/imunologia , Estudos de Casos e Controles , Proliferação de Células , Humanos , Metabolismo dos LipídeosRESUMO
Inflammation and immune dysfunction have been increasingly recognized as crucial mechanisms in atherogenesis. Modifications in cell lipid metabolism, plasma dyslipidaemia and particularly low high-density lipoprotein (HDL) levels occur both in atherosclerosis and in autoimmune rheumatic diseases (which are strongly associated with an increased risk of atherosclerosis), suggesting the presence of a crucial link. HDL, the plasma lipoprotein responsible for reverse cholesterol transport, is known for its several protective effects in the context of atherosclerosis. Among these, HDL immunomodulatory effects are possibly the less understood. Through the efflux of cholesterol from plasma cell membranes with the consequent disruption of lipid rafts and the interaction with the cholesterol transporters present in the plasma membrane, HDL affects both the innate and adaptive immune responses. Animal and human studies have demonstrated a predominance of HDL anti-inflammatory effects, despite some pro-inflammatory actions having also been reported. The HDL role on the modulation of the immune response is further suggested by the detection of low levels together with a dysfunctional HDL in patients with autoimmune diseases. Here, we review the current knowledge of the immune mechanisms of atherosclerosis and the modulatory effects HDL may have on them.
Assuntos
Aterosclerose/imunologia , Autoimunidade/imunologia , Imunidade/imunologia , Lipoproteínas HDL/imunologia , Animais , Doenças Autoimunes/imunologia , Humanos , Inflamação/imunologiaRESUMO
A 50-year-old man presented with dysphagia and proximal muscle weakness. He was diagnosed with immune-mediated necrotising myopathy associated with antibodies to the signal recognition particle. After an initial response following treatment with high-dose steroids, intravenous immunoglobulin and methotrexate, there was a relapse of the immune condition. The clinical deterioration occurred less than 2 months after disease onset. The refractoriness of this disease was characterised by an increase of the already severe muscle wasting that led to respiratory failure and progressive dysphagia, regardless of the immunosuppressant treatment. At this time the patient was referred to our department. He was restarted on intravenous pulses of methylprednisolone associated with intravenous cyclophosphamide, but with no effect. After 3 weeks, rituximab was started with a dramatic and progressive improvement. There were no complications associated with rituximab/cyclophosphamide treatment and the disease has been kept in remission, for the last 3 years.
Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Doenças Musculares/imunologia , Rituximab/uso terapêutico , Partícula de Reconhecimento de Sinal/imunologia , Doenças Autoimunes/sangue , Doenças Autoimunes/patologia , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Debilidade Muscular/sangue , Debilidade Muscular/tratamento farmacológico , Debilidade Muscular/imunologia , Debilidade Muscular/patologia , Doenças Musculares/sangue , Doenças Musculares/tratamento farmacológico , Doenças Musculares/patologia , NecroseRESUMO
OBJECTIVE: To review the likelihood of very long-term remission in patients with biopsy-proven LN attempting to identify good prognostic features. METHODS: We reviewed patients with LN whose renal biopsies showed World Health Organization (WHO) classes III, IV and V and who had a follow-up of at least 5 years between 1973 and 2008. We analysed demographic, clinical, laboratory and therapeutic parameters comparing those patients with (group A) and without (group B) 5 year remission. RESULTS: Of 191 LN patients followed, 105 patients met the strict inclusion criteria. Ninety-five patients were female. Mean age at diagnosis of lupus was 24.1 years (s.d. 10.7). ean age at diagnosis of LN was 28.4 years (s.d. 11.3). The mean duration of follow-up was 13.7 years (s.d. 14.1). Forty (38%) patients achieved 5 year remission, of whom 17 (16.2%) had remission for ≥15 years. The incidence of flares per year from 5 to 15 years was 7.9%; however, no flares were observed after 15 years of remission. The only distinguishing feature found in this study was the association of WHO class IV on kidney biopsy with LN progression (P = 0.03). CONCLUSION: Renal histology with WHO class IV predicted a poor long-term remission rate. Age, sex, ethnicity, serological parameters and treatment received did not predict long-term remission. Renal flares can occur up to 15 years after a patient has gone into remission.