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


RESULTS
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.


CONCLUSIONS
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.
Limoges University Hospital, Equipe Accueil 3842-Clinical Immunology Laboratory, Fr GEIST, Limoges, France ; Department of Internal Medicine, Limoges University Hospital, Limoges, France.
Anne-Laure
AL
Fauchais
Marie-Claude
MC
Lise
Pierre
P
Marget
François-Xavier
FX
Lapeybie
Holy
H
Bezanahary
Clothilde
C
Martel
Stéphanie
S
Dumonteil
Agnès
A
Sparsa
Fabrice
F
Lalloué
Kim
K
Ly
Marie
M
Essig
Elisabeth
E
Vidal
Marie-Odile
MO
Jauberteau
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology* / Q000628:therapy; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009414:Nerve Growth Factors / Q000097:blood* / Q000378:metabolism; D011788:Quality of Life
D009414:Nerve Growth Factors