Fauchais Anne-Laure, Lise Marie-Claude, Marget Pierre, Lapeybie François-Xavier, Bezanahary Holy, Martel Clothilde, Dumonteil Stéphanie, Sparsa Agnès, Lalloué Fabrice, Ly Kim, Essig Marie, Vidal Elisabeth, Jauberteau Marie-Odile
Limoges University Hospital, Equipe Accueil 3842-Clinical Immunology Laboratory, Fr GEIST, Limoges, France ; Department of Internal Medicine, Limoges University Hospital, Limoges, France.
PLoS One. 2013 Nov 1;8(11):e79414. doi: 10.1371/journal.pone.0079414. eCollection 2013.
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.
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.
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.
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.
神经营养因子在神经系统的发育和维持中起核心作用。然而，神经营养因子也可调节B细胞和T细胞的增殖与活化，尤其是通过自分泌环。我们推测，系统性红斑狼疮（SLE）患者血清和淋巴细胞中的神经营养因子水平可能失调，并可能反映该疾病的临床症状。
对26例SLE患者和26例对照者测定血清（ELISA检测）和淋巴细胞（流式细胞术）中的神经营养因子。通过ELISA评估SLE患者和对照者的Th1（干扰素-γ）和Th2（IL-10）谱以及BAFF的血清浓度。
我们已证明，SLE患者的NGF和BDNF血清水平均高于健康对照者（p = 0.003和p <0.001），与Th1或Th2谱无关。仅在严重狼疮发作（即SLEDAI≥10）中发现血清NT-3水平升高（p = 0.003），且与补体激活显著相关（CH 50降低，Γ=-0.28，p = 0.03）。此外，血清NGF水平与循环T调节细胞数量呈负相关（Γ= 0.48，p = 0.01）。在循环B细胞中，SLE患者的NGF和BDNF产生均高于健康对照者。特别是，分泌NGF的B细胞数量与补体水平降低相关（p = 0.05）。SLE发作治疗1个月后，BDNF水平下降；相比之下，NGF和NT-3水平保持不变。
本研究表明，SLE患者血清和B细胞中的NGF和BDNF水平均升高，提示该疾病中神经营养因子产生途径失调。这些结果必须在更大规模的初发SLE患者研究中得到证实，以避免先前免疫调节治疗对神经营养因子水平的潜在混杂影响。
