RESUMEN
BACKGROUND: Neurotrophins play a central role in the development and maintenance of the nervous system. However, neurotrophins can also modulate B and T cell proliferation and activation, especially via autocrine loops. We hypothesized that both serum and lymphocytic neurotrophin levels may be deregulated in systemic Lupus erythematosus (SLE) and may reflect clinical symptoms of the disease. METHODS: Neurotrophins in the serum (ELISA tests) and lymphocytes (flow cytometry) were measured in 26 SLE patients and 26 control subjects. Th1 (interferon-γ) and Th2 (IL-10) profiles and serum concentration of BAFF were assessed by ELISA in the SLE and control subjects. FINDINGS: We have demonstrated that both NGF and BDNF serum levels are higher in SLE patients than healthy controls (p=0.003 and p<0.001), independently of Th1 or Th2 profiles. Enhanced serum NT-3 levels (p=0.003) were only found in severe lupus flares (i.e. SLEDAI ≥ 10) and significantly correlated with complement activation (decreased CH 50, Γ=-0.28, p=0.03). Furthermore, there was a negative correlation between serum NGF levels and the number of circulating T regulatory cells (Γ=0.48, p=0.01). In circulating B cells, production of both NGF and BDNF was greater in SLE patients than in healthy controls. In particular, the number of NGF-secreting B cells correlated with decreased complement levels (p=0.05). One month after SLE flare treatment, BDNF levels decreased; in contrast, NGF and NT-3 levels remained unchanged. CONCLUSION: This study demonstrates that serum and B cell levels of both NGF and BDNF are increased in SLE, suggesting that the neurotrophin production pathway is deregulated in this disease. These results must be confirmed in a larger study with naive SLE patients, in order to avoid the potential confounding influence of prior immune-modulating treatments on neurotrophin levels.
Asunto(s)
Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Linfocitos/metabolismo , Factores de Crecimiento Nervioso/sangre , Adulto , Linfocitos B/inmunología , Linfocitos B/metabolismo , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Humanos , Lupus Eritematoso Sistémico/terapia , Linfocitos/inmunología , Masculino , Factores de Crecimiento Nervioso/metabolismo , Calidad de VidaRESUMEN
Neurotensin, a neuropeptide growth factor, and its two specific neurotensin receptors, NTSR1 and NTSR2, were shown to be expressed by human B cell lines. Another NTSR, sortilin, which is common to neurotensin and neurotrophins, was also detected as we have previously described. Neurotensin was functional in B cell lines; it induced their proliferation and inhibited apoptosis induced by serum deprivation or Fas activation. Quantitative study of gene expression in two malignant B cell diseases showed that NTSR2 was overexpressed, NTSR1 decreased, and neurotensin was unexpressed in B cell leukemia patient's cells, as compared with healthy B cells. However, these expressions did not significantly change in large diffuse B cell lymphoma lymph nodes compared with benign ones. This study points out that neurotensin and its two specific receptors are expressed in human B lymphocytes. Such expressions were not described, and their relationship in B cell diseases, especially in chronic B cell leukemia, needs to be considered further in regard to these findings.