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Serum and lymphocytic neurotrophins profiles in systemic lupus erythematosus: a case-control study.

Fauchais AL, Lise MC, Marget P, Lapeybie FX, Bezanahary H, Martel C, Dumonteil S, Sparsa A, Lalloué F, Ly K, Essig M, Vidal E, Jauberteau MO - PLoS ONE (2013)

Bottom Line: 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).In particular, the number of NGF-secreting B cells correlated with decreased complement levels (p=0.05).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.

View Article: PubMed Central - PubMed

Affiliation: Limoges University Hospital, Equipe Accueil 3842-Clinical Immunology Laboratory, Fr GEIST, Limoges, France ; Department of Internal Medicine, Limoges University Hospital, Limoges, France.

ABSTRACT

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.

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Percentage of B lymphocytes (flow cytometry) expressing NGF (A) and BDNF (B) (SLE, grey boxes) and healthy controls (Controls, white boxes).The boxes represent the 50th percentile, the bars outside the boxes show the 10th and 90th percentiles, and the horizontal black lines represent median values. Significant differences were assessed with Mann-Whitney tests.
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pone-0079414-g005: Percentage of B lymphocytes (flow cytometry) expressing NGF (A) and BDNF (B) (SLE, grey boxes) and healthy controls (Controls, white boxes).The boxes represent the 50th percentile, the bars outside the boxes show the 10th and 90th percentiles, and the horizontal black lines represent median values. Significant differences were assessed with Mann-Whitney tests.

Mentions: The numbers of B cells producing NGF and BDF were greater in the SLE group than in healthy controls (NGF, 29.3 ± 31.3 vs 11.3 ± 20.9, p=0.02; BDNF, 71.2 ± 30.9 vs 47.9 ± 27.8, p=0.03, Figure 5). Cell numbers were independent of serum NGF, BDNF and NT-3 concentrations. In contrast, the numbers of NT-3-CD19-positive cells were similar in the two groups (72.4 ± 29.7 vs 64.7 ± 29.1, NS).


Serum and lymphocytic neurotrophins profiles in systemic lupus erythematosus: a case-control study.

Fauchais AL, Lise MC, Marget P, Lapeybie FX, Bezanahary H, Martel C, Dumonteil S, Sparsa A, Lalloué F, Ly K, Essig M, Vidal E, Jauberteau MO - PLoS ONE (2013)

Percentage of B lymphocytes (flow cytometry) expressing NGF (A) and BDNF (B) (SLE, grey boxes) and healthy controls (Controls, white boxes).The boxes represent the 50th percentile, the bars outside the boxes show the 10th and 90th percentiles, and the horizontal black lines represent median values. Significant differences were assessed with Mann-Whitney tests.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815153&req=5

pone-0079414-g005: Percentage of B lymphocytes (flow cytometry) expressing NGF (A) and BDNF (B) (SLE, grey boxes) and healthy controls (Controls, white boxes).The boxes represent the 50th percentile, the bars outside the boxes show the 10th and 90th percentiles, and the horizontal black lines represent median values. Significant differences were assessed with Mann-Whitney tests.
Mentions: The numbers of B cells producing NGF and BDF were greater in the SLE group than in healthy controls (NGF, 29.3 ± 31.3 vs 11.3 ± 20.9, p=0.02; BDNF, 71.2 ± 30.9 vs 47.9 ± 27.8, p=0.03, Figure 5). Cell numbers were independent of serum NGF, BDNF and NT-3 concentrations. In contrast, the numbers of NT-3-CD19-positive cells were similar in the two groups (72.4 ± 29.7 vs 64.7 ± 29.1, NS).

Bottom Line: 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).In particular, the number of NGF-secreting B cells correlated with decreased complement levels (p=0.05).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.

View Article: PubMed Central - PubMed

Affiliation: Limoges University Hospital, Equipe Accueil 3842-Clinical Immunology Laboratory, Fr GEIST, Limoges, France ; Department of Internal Medicine, Limoges University Hospital, Limoges, France.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus