Serum and Lymphocytic Neurotrophins Profiles in Systemic Lupus Erythematosus: a Case-Control Study

Abstract

BackgroundNeurotrophins 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.MethodsNeurotrophins 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.FindingsWe 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.ConclusionThis 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.

Peripheral levels of brain-derived neurotrophic factor and S100B in neuropsychiatric systemic lupus erythematous

“…16 Similarly, few reports are available regarding peripheral BDNF levels in SLE and data are conflicting. [32][33][34] BDNF is the most abundant neurotrophin in brain tissue and has been implicated in several neurological and psychiatric disorders. 35 It is difficult to interpret the discrepant data that have suggested both increases and decreases in peripheral BDNF in SLE patients and the association or not with NP manifestation.…”

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients

“…To our knowledge, ours is the first report of PBMC production of neurotrophins in SLE. One other study assessed neurotrophin expression within B and T cells with flow cytometry, measuring the number of neurotrophin-producing cells, without quantifying the actual neurotrophin expression [24]. Our approach to PBMC assessment was also used in other disorders, such as multiple sclerosis [25, 19].…”

“…For instance, NGF was shown to downregulate the monocytic inflammatory response via the trkA receptor [34]. On the other hand, neurotrophin overexpression in B cells of SLE patients was suggested as a hallmark of pathological activation [24]. Interestingly, it was shown that NGF might actually disrupt peripheral tolerance in psoriatic arthritis and rheumatoid arthritis, where it induced T cell proliferation and activation and decreased their sensitivity to TNF-α-induced apoptosis [35].…”

Brain‑derived neurotrophic factor in autoimmune inflammatory diseases (Review)

“…Recently, serum BDNF levels in SLE have been receiving increasing attention ( 54-59 ) and have been linked to various clinical parameters, suggesting the involvement of BDNF in the pathogenesis and progression of SLE. Fauchais et al ( 58 ) indicated that the serum levels of BDNF and the SLE disease activity index (SLEDAI) were not correlated. Although BDNF levels were reduced after treatment, they remained higher in patients with SLE than in healthy controls.…”