RESUMEN
A novel 'multistep molecular mimicry' mechanism for induction of rheumatoid arthritis (RA) by bacterial antigens that activate T lymphocytes previously 'educated' by peptides derived from a class of human histocompatibility antigens is reported here. These antigens have the amino acid sequence QKRAA, which is also present on the Escherichia coli heat-shock protein dnaJ. Synovial fluid cells of early RA patients have strong immune responses to the bacterial antigen, but cells from normal subjects or controls with other autoimmune diseases do not. The activated T cells may cross-react with autologous dnaJ heat-shock proteins that are expressed at synovial sites of inflammation. Our findings may have direct relevance to new strategies for the immune therapy of RA.
Asunto(s)
Artritis Reumatoide/inmunología , Autoinmunidad/inmunología , Proteínas Bacterianas/farmacología , Proteínas de Choque Térmico/farmacología , Secuencia de Aminoácidos , Especificidad de Anticuerpos , Artritis Reumatoide/genética , Autoinmunidad/genética , Escherichia coli/inmunología , Proteínas de Escherichia coli , Femenino , Antígenos HLA/inmunología , Antígenos HLA/metabolismo , Proteínas del Choque Térmico HSP40 , Humanos , Activación de Linfocitos/efectos de los fármacos , Masculino , Datos de Secuencia Molecular , Péptidos/inmunología , Péptidos/metabolismo , Unión Proteica/inmunología , Factores de TiempoRESUMEN
The aim of this study was to assess the accuracy of the copper/zinc ratio (Cu/Zn ratio) in the evaluation of a large group of patients with digestive cancer compared to gender and age-matched control subjects. A total of 282 patients was studied and separated into three groups: group I (n = 75), patients with digestive cancer, group II (n = 112), patients with benign digestive disease, and group III (n = 95), healthy subjects. Serum levels of copper and zinc were measured by atomic absorption spectrophotometry. The results showed that the serum levels of copper (mg/dL) in patients with digestive cancer (91.6 +/- 27.3, p < 0.05) were significantly higher than in patients with benign digestive disease (75.8 +/- 19.8) or healthy subjects (54.4 +/- 8.9) and the serum levels of zinc (mg/dl) were significantly lower (68.7 +/- 21.9, p < 0.05) compared to benign digestive disease patients (80.1 +/- 18.7) or healthy subjects (100 +/- 11.4 mg/dl). The Cu/Zn ratio was also significantly higher in patients with digestive cancer (1.45 +/- .58, p < 0.05) than those with benign digestive disease (0.95 +/- 0.28) or healthy subjects (0.55 +/- 0.13). Considering a cutoff value of 0.87, the sensitivity of the copper/zinc ratio was 82.2%, with a specificity of 65.7%, a positive predictive value of 45.8% and a negative predictive value of 91.3%. In conclusion, Cu/Zn ratio was found to be considerably higher in patients with digestive cancer compared to age- and gender-matched controls, with a sensitivity of 82.2% that might be useful in the evaluation of suspected malignancy.