RESUMEN
While most of our understanding of immune dysfunction in dialysis patients involves alterations in CD28-CD80/86 signalling, nothing is known of CD46-mediated co-stimulation of T cells in these patients. Because C3b/C4b bind to CD46 and complement activation occurs during haemodialysis (HD), we addressed whether CD46-mediated T cell activation is altered in HD (n = 9), peritoneal dialysis (PD) (n = 10) and predialysis patients (n = 8) compared to healthy controls (HC) (n = 8). T cell surface markers, T cell proliferation and interleukin (IL)-10 production were studied in CD4(+)T cells. In addition, CD46 splice-variants and IL-10 promoter gene polymorphisms were studied by reverse transcription (RT) or amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), respectively. In all uraemic patients, irrespective of the stage of renal insufficiency or dialysis modality, a significant increase in the percentage of CD25 positivity in naive CD4(+)T cells was found (64% +/- 21%versus 23% +/- 18%, P < 0.001). Lymphocytes of HD patients proliferated in greater numbers and produced more IL-10 after co-stimulation with anti-CD46 than after co-stimulation with anti-CD28. This was also found in CD4(+)T cells of PD patients, albeit to a lesser extent. In contrast, with T cells of predialysis patients and of HC, co-stimulation via CD28 was more efficient. The observed alterations in T cell proliferation and IL-10 production were associated neither with CD46 splice variants nor with IL-10 promoter gene polymorphisms. Lymphocytes of HD patients show an increased response on CD46 co-stimulation. These data suggest that ongoing complement activation in HD patients may lead to alterations in acquired immunity.
Asunto(s)
Antígenos CD/inmunología , Linfocitos T CD4-Positivos/inmunología , Activación de Complemento , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/terapia , Glicoproteínas de Membrana/inmunología , Diálisis Renal , Anciano , Anciano de 80 o más Años , Empalme Alternativo , Análisis de Varianza , Antígenos CD/genética , Estudios de Casos y Controles , Proliferación Celular , Femenino , Humanos , Interleucina-10/inmunología , Activación de Linfocitos , Masculino , Proteína Cofactora de Membrana , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Diálisis Peritoneal , Polimorfismo Genético , Regiones Promotoras Genéticas , Estadísticas no ParamétricasRESUMEN
The hypothesis that limiting the knee-flexion range increases the peak hip-extension moment while transferring from sitting to standing was tested by filming (100 fps) ten normal human volunteers. With the knees flexed 105 degrees from full extension (0 degrees) the mean (+/- 1 S.D.) peak hip-extension moment was 142 (+/- 37) Nm. With the knees flexed only 75 degrees subjects threw their arms and trunks forward to a greater extent, with a peak moment of 253 (+/- 65) Nm (p less than 0.0001). If the peak moments rise to a similar degree in patients with arthritis and limited knee-flexion range, they may accelerate hip joint damage or the loosening of hip endoprostheses.