RESUMEN
The immunopathological events in the kidneys of lupus nephritis (LN) patients are poorly understood due in part to the difficulty in acquiring serial biopsies and the inherent limitations in their analysis. To identify a means to circumvent these limitations, we investigated whether immune cells of kidney origin are present in patient urine and whether they correlate with kidney pathology. Flow cytometry analysis was performed on peripheral blood and urine cells of 69 SLE patients, of whom 41 were LN patients. In addition, type I IFN (IFNα/ß) levels were determined in plasma and urine by bioassay. Approximately 60% of non-LN patients had urine lymphocytes. In these patients, T cells were always present and predominantly CD8(+), while B cells were either absent or a mixture of naïve and memory B cells. In contrast, >90% of LN patients had urine lymphocytes. In half, the B and T cells resembled those in non-LN patient urine; however, in the remaining patients, the B cells were exclusively Ig-secreting plasmablasts or plasma cells (PB/PCs) and the T cells were predominantly CD4(+). In addition, pDCs and IFNα/ß frequently accompanied PB/PCs. The majority of patients with urine PB/PCs presented with proliferative nephritis and a significant loss of kidney function, which in some cases had progressed to end stage renal disease (ESRD). In conclusion, urine can provide access to cells of kidney resident populations for phenotypic and functional characterization. Analysis of these cells provides insight into the kidney immunopathology and may serve as biomarkers to identify patients at risk for developing LN and progressing to ESRD.
Asunto(s)
Sistema Inmunológico/citología , Interferón Tipo I/inmunología , Riñón/inmunología , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/inmunología , Orina/citología , Adulto , Linfocitos B/inmunología , Linfocitos T CD8-positivos/inmunología , Línea Celular , Células Dendríticas/inmunología , Femenino , Citometría de Flujo , Humanos , Sistema Inmunológico/inmunología , Memoria Inmunológica/inmunología , Interferón Tipo I/sangre , Interferón Tipo I/orina , Interferón-alfa/sangre , Interferón-alfa/inmunología , Interferón-alfa/orina , Interferón beta/sangre , Interferón beta/inmunología , Interferón beta/orina , Riñón/patología , Fallo Renal Crónico/sangre , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/orina , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/orina , Nefritis Lúpica/sangre , Nefritis Lúpica/orina , Masculino , Células Plasmáticas/inmunologíaRESUMEN
The aim of this study was to estimate the frequency of HSV and/or CMV among the pathogens causing intrauterine infections (IUI) and to investigate their impact on the level of proinflammatory cytokines in premature neonatal infants. Examinations were performed in 3 neonatal groups: 1) premature neonates with clinical manifestations of IUI; 2) those without IUI; 3) full-term newborns. In group 1, viral (HSV and/or CMV) and bacterial infections were detectable with the same frequency. Quantitative analysis of plasma IL-6 and IL-8 levels and the induced production of these cytokines by blood cells in vitro showed that in Group 1 neonates, IL-6 and IL-8 concentrations were substantially higher and the induced production of these cytokines was lowerthan those in Group 3. The detection of HSV and/or CMV markers in premature newborn infants was attended by a statistically significant rise in plasma IL-6 levels; the identification of the opportunistic bacterial microflora correlated with the higher concentration of IL-8. In Group 1, wiferon produced an immunomodulatory effect, by lowering IL-8 concentrations to the level observed in Group 3.