Neurocognitive Effects of Cocoa and Red-Berries Consumption in Healthy Adults.

In recent decades, the elderly population has increased at higher rates than any other population group, resulting in an increase in age-related diseases such as neurodegenerative and cognitive impairment. To address this global health problem, it is necessary to search for new dietary strategies that can prevent the main neurocognitive problems associated with the ageing process. Therefore, the aim of the present study was to analyze the effect of cocoa flavanols and red berry anthocyanins on brain-derived neurotrophic factor (BDNF) and nerve growth factor receptor (NGF-R) and to stablish the possible improvement in cognitive performance by using a battery of neurocognitive tests that included the Verbal Learning Test Spain-Complutense, the Spatial Recall Test 10/36 BRB-N, the Wechsler Adult Intelligence Scale III and IV, the STROOP Task and the Tower of London Test. A randomized, double-blind, parallel-group study was performed in 60 healthy volunteers between 50 and 75 years old who consumed a cocoa powder, a red berries mixture or a combination of both for 12 weeks. After the intervention, we observed a reduction in the time needed to start (p = 0.031) and finish (p = 0.018) the neurocognitive test known as the Tower of London in all groups, but the decrease in time to finish the task was more pronounced in the intervention with the combination of cocoa-red berries group. We failed to show any significant difference in BDNF and NGF-R sera levels. However we found a negative correlation between BDNF and the number of movements required to finish the TOL in women (p = 0.044). In conclusion, our study showed an improvement in executive function, without any change in neurotrofin levels, for all intervention arms.

Updated overview on interplay between physical exercise, neurotrophins, and cognitive function in humans.

The many important benefits of physical exercise also encompass maintenance or improvement of cognitive functions. Among the various mechanisms underlying the association between physical exercise and brain health, recent evidence attests that neurotrophin receptor signaling may have an important role, because the activation of this pathway leads to growth and differentiation of new neurons and synapses, supports axonal and dendritic growth, fosters synaptic plasticity, and preserves survival of existing neurons. In this review of published evidence, we highlight that a positive relationship exists between physical exercise and circulating brain-derived neurotrophic factor levels and that the postexercise variation of this molecule is associated with improvement of neurocognitive functioning. Less clear evidence has instead been published for other neurotrophins, such as nerve growth factor, neurotrophin-3, and neurotrophin-4. Overall, promotion of adequate volumes and intensities of physical exercise (i.e., approximately 3 months of moderate-intensity aerobic exercise, with 2-3 sessions/week lasting not less than 30 min) may hence be regarded as an inexpensive and safe strategy for boosting brain-derived neurotrophic factor release, thus preserving or restoring cognitive functions.

p75 and neural cell adhesion molecule 1 can identify pathologic Schwann cells in peripheral neuropathies.

OBJECTIVE: Myelinated Schwann cells (SCs) in adult peripheral nerves dedifferentiate into immature cells in demyelinating neuropathies and Wallerian degeneration. This plastic SC change is actively involved in the myelin destruction and clearance as demyelinating SCs (DSCs). In inherited demyelinating neuropathy, pathologically differentiated and dysmyelinated SCs constitute the main nerve pathology. METHODS: We investigated whether this SC plastic status in human neuropathic nerves could be determined by patient sera to develop disease-relevant serum biomarkers. Based on proteomics analysis of the secreted exosomes from immature SCs, we traced p75 neurotrophin receptor (p75) and neural cell adhesion molecule 1 (NCAM) in the sera of patients with peripheral neuropathy. RESULTS: Enzyme-linked immunosorbent assay (ELISA) revealed that p75 and NCAM were subtype-specifically expressed in the sera of patients with peripheral neuropathy. In conjunction with these ELISA data, pathological analyses of animal models and human specimens suggested that the presence of DSCs in inflammatory neuropathy and of supernumerary nonmyelinating or dysmyelinating SCs in inherited neuropathy could potentially be distinguished by comparing the expression profiles of p75 and NCAM. INTERPRETATION: This study indicates that the identification of disease-specific pathological SC stages might be a valuable tool for differential diagnosis of peripheral neuropathies.

Neurotrophin Receptor p75 mRNA Level in Peripheral Blood Cells of Patients with Alzheimer's Disease.

The neurotrophin receptor p75 (p75NTR) plays important roles in regulating amyloid-beta (Aß) metabolism in the brain. The expression of p75NTR is altered in the brain of patients with Alzheimer's disease (AD). In this study, we aimed to evaluate whether p75NTR mRNA level in the peripheral blood cells is changed among AD patients and its potential to be a biomarker for AD. The study subjects included 26 patients with AD (PiB-PET positive) and 28 cognitively normal controls (PiB-PET negative). RNA was extracted from peripheral blood cells of fast blood. p75NTR mRNA was measured using quantitative real-time PCR assay. p75NTR mRNA levels in blood cells were comparable between AD patients and controls. p75NTR mRNA levels in blood cells were not correlated with MMSE scores, ApoE genotypes, gender, and age. p75NTR mRNA expression in blood cells is not changed in AD patients and is unlikely to be a biomarker for AD.

RNA Sequencing of Peripheral Blood Revealed that the Neurotropic TRK Receptor Signaling Pathway Shows Apparent Correlation in Recovery Following Spinal Cord Injury at Small Cohort.

Spinal cord injury (SCI) can be lethal; however, the precise mechanisms underlying healing are unclear, limiting the development of effective therapies. In this study, the molecular mechanisms involved in SCI were investigated. Clinical peripheral blood samples from normal individuals and patients with incomplete SCI (ISCI) and complete SCI (CSCI) were analyzed by RNA-Seq. The expression levels of EPHA4, CDK16, BAD, MAP2 Normal 2, EGR, and RHOB differed significantly between the SCI group and normal individuals, and these results were verified by q-PCR. A gene ontology (GO) enrichment analysis showed that differentially expressed genes were mostly enriched for the neurotrophin TRK receptor signaling pathway. We verified the expression of neurotrophic factors and found that they were all expressed most highly in the SCI group. The results of this study demonstrate that neurotrophic factors are highly expressed after SCI and the neurotrophin TRK receptor signaling pathway may be involved in the initiation of nerve system regeneration.

ProBDNF/p75NTR/sortilin pathway is activated in peripheral blood of patients with alcohol dependence.

Alcohol dependence is a worldwide problem with a great social and economic burden in many countries. A number of studies have suggested that BDNF (mature BDNF) and its precursor (proBDNF) play important roles in the alcohol dependence. However, what roles of the mBDNF/proBDNF pathways play during the pathological process of alcohol dependence are not clearly understood. In our clinical study, peripheral blood was sampled from 30 male patients with alcohol dependence and 50 healthy males (as control). The protein levels of proBDNF, p75NTR, sortilin, mBDNF, TrkB and mRNA levels of BDNF, p75NTR, sortilin, and TrkB were detected in the peripheral blood in our study. We found that the protein levels of proBDNF and p75NTR were increased, but not the sortilin protein level; while the TrkB protein level was decreased in the alcohol dependence patients compared with healthy controls. Moreover, the mRNA levels of p75NTR and sortilin from the lymphocytes were slightly increased; while BDNF and TrkB were significantly decreased. The ELISA results of mBDNF and TrkB were declined in the alcohol dependence group. The levels of mBDNF and TrkB were negatively correlated with the average amount of daily ethanol consumption, and the levels of proBDNF, p75NTR and sortilin were positively correlated with the average amount of ethanol consumption per day. The ratio of proBDNF to mBDNF was altered in alcohol dependence patients. The balance between the proBDNF/p75NTR and mBDNF/TrkB signalling pathways appeared dysregulated in alcohol dependence. Our results suggested that both pathways may participate in the complex processes of alcohol dependence.

Assessing the serum concentration levels of NT-4/5, GPX-1, TNF-α, and l-arginine as biomediators of depression severity in first depressive episode patients with and without posttraumatic stress disorder.

BACKGROUND: Neurotrophin-4/5 (NT-4/5) and glutathione peroxidase-1 (GPX-1) have been shown to play a major role in neuronal processes including depression and posttraumatic stress disorder (PTSD). They protect the body from oxidative damage by affecting neuronal growth, development and plasticity. The aim of the study was to evaluate the concentrations of NT-4/5, GPX-1, tumor necrosis factor-α (TNF-α), and l-arginine in patients suffering from varying levels of depression severity, PTSD, and depression comorbid with PTSD. METHODS: The study involved 460 participants, 360 of whom were diagnosed with different types of depressive episodes. They included: 60 patients with mild depression (MD), 60 patients with moderate depression (MOD), 60 patients with severe depression (SeD), 60 patients with MD and PTSD (MD+PTSD), 60 patients with MOD and PTSD (MOD+PTSD), 60 patients with SeD and PTSD (SeD+PTSD), and 60 patients with PTSD alone. Each group of 60 subjects comprised 30 females and 30 males. The control group comprised 40 subjects. The 10th revision of the International Statistical Classification of Diseases and Related Health Problems was utilized to diagnose depression and PTSD. At 7a.m. blood samples were collected and serum NT-4/5, GPX-1, TNF-α and l-arginine concentrations were assessed using the ELISA method. RESULTS: Depressive episodes with and without PTSD and PTSD alone became more severe as the levels of TNF-α, l-arginine increased and the levels of NT-4/5, GPX-1 decreased. CONCLUSION: l-arginine, TNF-α, NT-4/5 and GPX-1 can be markers of depression severity in both males and females with first depressive episode with or without posttraumatic stress disorder.

Combined serum levels of multiple proteins in tPA-BDNF pathway may aid the diagnosis of five mental disorders.

Mental disorders are severe, disabling conditions with unknown etiology and are commonly misdiagnosed when clinical symptomology criteria are solely used. Our previous work indicated that combination of serum levels of multiple proteins in tissue plasminogen activator (tPA)-brain-derived neurotrophic factor (BDNF) pathway improved accuracy of diagnosis of major depressive disorder (MDD). Here, we measured serum levels of tPA, plasminogen activator inhibitor-1 (PAI-1), BDNF, precursor-BDNF (proBDNF), tropomyosin-related kinase B (TrkB) and neurotrophin receptor p75 (p75NTR) in patients with paranoid schizophrenia (SZ, n = 34), MDD (n = 30), bipolar mania (BM, n = 30), bipolar depression (BD, n = 22), panic disorder (PD, n = 30), and healthy controls (HCs, n = 30) by Enzyme-linked immunosorbent assay kits. We used receiver operating characteristic (ROC) curve to analyze diagnostic potential of these proteins. We found, compared with HCs, that serum tPA and proBDNF were lower in SZ, BM and BD; TrkB was lower in SZ and BD; and p75NTR was declined in SZ and BM. ROC analysis showed that combined serum level of tPA, PAI-1, BDNF, proBDNF, TrkB and p75NTR was better than any single protein in accuracy of diagnosis and differentiation, suggesting that the combination of multiple serum proteins levels in tPA-BDNF pathway may have a potential for a diagnostic panel in mental disorders.

ß-NGF and ß-NGF receptor upregulation in blood and synovial fluid in osteoarthritis.

Osteoarthritis (OA) of the knee is the most common form of non-traumatic joint disease. Previous studies have shown the involvement of ß-NGF and its receptors TrKA and p75NTR in OA-related pain, but their role in its pathogenesis is still unclear. The aim of our study was to investigate the amount of ß-NGF and the expression levels of its receptors on cells isolated from synovial fluid and blood from OA patients who had undergone total knee arthroplasty, in order to check any possible correlation with the disease staging. Our results show a progressive stage-related increase of ß-NGF and its receptors both in serum and synovial fluid. Furthermore, with respect to control subjects, OA patients show an increased amount of inflammatory monocytes along with an increased expression of ß-NGF, TrKA and p75NTR. In conclusion, our study suggests a stage-related modulation of ß-NGF and its receptors in the inflammatory process of OA.

Changes in Plasma ß-NGF and Its Receptors Expression on Peripheral Blood Monocytes During Alzheimer's Disease Progression.

Alzheimer's disease (AD), the most common cause of dementia, is characterized by the deposition of extracellular amyloid-ß (Aß) plaques and intracellular neurofibrillary tangles, and by neuroinflammation. During the pathogenesis of AD, monocyte-macrophage lineage cells become increasingly ineffective in clearing Aß deposits, less able to differentiate, and shift toward pro-inflammatory processes. Beta-nerve growth factor (ß-NGF) and its receptors, TrKA and p75NTR, produce several biological responses, including cell apoptosis and survival, and inflammation. In the central nervous system, the involvement of these receptors in several critical hallmarks of AD is well known, but their role in circulating monocytes during the progression of dementia is unclear. We investigated the relationship between plasma ß-NGF concentration and TrkA/p75NTR receptor expression in monocytes of patients with mild cognitive impairment (MCI), mild AD, and severe AD. We observed that plasma ß-NGF concentration was increased with a higher expression of TrKA, but not of p75NTR, in monocytes from patients with MCI and mild AD, whereas ß-NGF concentration and TrKA expression were decreased and p75NTR expression was increased, associated with caspase 3-mediated apoptosis, in patients with severe AD. In our study, we show evidence of variation in plasmatic ß-NGF and monocytic TrkA/p75NTR receptor expression during the progression of dementia. These novel findings add evidence to support the hypothesis for the involvement of ß-NGF and its receptors on monocytes during AD progression.

Detection of circulating tumor cells by p75NTR expression in patients with esophageal cancer.

BACKGROUND: The p75 neurotrophin receptor (p75NTR) is a cancer stem cell (CSC) marker in esophageal squamous cell carcinoma (ESCC). This study aimed to assess the use of p75NTR in detecting circulating tumor cells (CTCs) in ESCC. METHODS: Peripheral blood mononuclear cell expression of epithelial cell adhesion molecule (EpCAM) and p75NTR was detected in 23 ESCC patients (13 received chemo- or chemoradiotherapy and 10 received curative surgery) and 10 healthy controls by flow cytometry. RESULTS: EpCAM+p75NTR+ cell counts (average±SD) were significantly higher in patients (n=23, 16.0±18.3) compared to controls (n=10, 0.4±0.9, p=0.013). The sensitivity and specificity to differentiate ESCC patients from controls were 78.3 and 100% (cut-off value 4.0), respectively. EpCAM+p75NTR+, but not EpCAM+p75NTR- cell counts, correlated with clinically diagnosed distant metastasis (n=13, p=0.006) and pathological venous invasion in resected primary tumors (n=10, p=0.016). Malignant cytology was microscopically confirmed in isolated EpCAM+p75NTR+ cells with immunocytochemical double staining. CONCLUSIONS: p75NTR is suggested to be a useful marker for clinically significant CTCs, which exhibit highly metastatic features in ESCC.

Bone Marrow Stromal Antigen 2 Is a Novel Plasma Biomarker and Prognosticator for Colorectal Carcinoma: A Secretome-Based Verification Study.

BACKGROUND: The cancer cell secretome has been recognized as a valuable reservoir for identifying novel serum/plasma biomarkers for different cancers, including colorectal cancer (CRC). This study aimed to verify four CRC cell-secreted proteins (tumor-associated calcium signal transducer 2/trophoblast cell surface antigen 2 (TACSTD2/TROP2), tetraspanin-6 (TSPAN6), bone marrow stromal antigen 2 (BST2), and tumor necrosis factor receptor superfamily member 16 (NGFR)) as potential plasma CRC biomarkers. METHODS: The study population comprises 152 CRC patients and 152 controls. Target protein levels in plasma and tissue samples were assessed by ELISA and immunohistochemistry, respectively. RESULTS: Among the four candidate proteins examined by ELISA in a small sample set, only BST2 showed significantly elevated plasma levels in CRC patients versus controls. Immunohistochemical analysis revealed the overexpression of BST2 in CRC tissues, and higher BST2 expression levels correlated with poorer 5-year survival (46.47% versus 65.57%; p = 0.044). Further verification confirmed the elevated plasma BST2 levels in CRC patients (2.35 ± 0.13 ng/mL) versus controls (1.04 ± 0.03 ng/mL) (p < 0.01), with an area under the ROC curve (AUC) being 0.858 comparable to that of CEA (0.867). CONCLUSION: BST2, a membrane protein selectively detected in CRC cell secretome, may be a novel plasma biomarker and prognosticator for CRC.

Differential levels of p75NTR ectodomain in CSF and blood in patients with Alzheimer's disease: a novel diagnostic marker.

Alzheimer's disease (AD) is the primary cause of dementia in the elderly. The ectodomain of p75 neurotrophin receptor (p75NTR-ECD) has been suggested to play important roles in regulating beta-amyloid (Aß) deposition and in protecting neurons from the toxicity of soluble Aß. However, whether and how the serum and cerebrospinal fluid (CSF) levels of p75NTR-ECD change in patients with AD are not well documented. In the present study, we determined the concentrations of serum p75NTR-ECD in an AD group, a Parkinson disease group and a stroke group, as well as in a group of elderly controls without neurological disorders (EC). We also determined the levels of CSF p75NTR-ECD in a subset of the AD and EC groups. Our data showed that a distinct p75NTR-ECD profile characterized by a decreased CSF level and an increased serum level was present concomitantly with AD patients but not with other diseases. p75NTR-ECD levels in both the serum and CSF were strongly correlated with Mini-Mental State Examination (MMSE) scores and showed sound differential diagnostic value for AD. Moreover, when combining CSF Aß42, CSF Aß42/40, CSF ptau181 or CSF ptau181/Aß42 with CSF p75NTR-ECD, the area under the receiver operating characteristic curve (AUC) and diagnostic accuracies improved. These findings indicate that p75NTR-ECD can serve as a specific biomarker for AD and the determination of serum and CSF p75NTR-ECD levels is likely to be helpful in monitoring AD progression.

Neurotrophic factors in tension-type headache.

Neurotrophic factors (NF) are involved in pain regulation and a few studies have suggested that they may play a pathophysiological role in primary headaches. The aim of this study was to investigate NF levels in patients with tension type headache (TTH). We carried out a cross sectional study including 48 TTH patients and 48 age and gender matched controls. Beck Depression and Anxiety Inventories, and Headache Impact Test were recorded. Serum levels of NF were determined by ELISA. There were not significant differences between NF levels between TTH patients and controls. Patients with chronic and episodic TTH had not significant differences in NF levels. The presence of headache at the time of evaluation did not significantly alter the levels of NF. Depression and anxiety scores as well as headache impact did not correlate with NF levels. Our study suggest that the serum levels of NF are not altered in TTH.

Neurotrophic factors in tension-type headache / Fatores neurotróficos na cefaleia do tipo tensional

Neurotrophic factors (NF) are involved in pain regulation and a few studies have suggested that they may play a pathophysiological role in primary headaches. The aim of this study was to investigate NF levels in patients with tension type headache (TTH). We carried out a cross sectional study including 48 TTH patients and 48 age and gender matched controls. Beck Depression and Anxiety Inventories, and Headache Impact Test were recorded. Serum levels of NF were determined by ELISA. There were not significant differences between NF levels between TTH patients and controls. Patients with chronic and episodic TTH had not significant differences in NF levels. The presence of headache at the time of evaluation did not significantly alter the levels of NF. Depression and anxiety scores as well as headache impact did not correlate with NF levels. Our study suggest that the serum levels of NF are not altered in TTH.

Os fatores neurotróficos (FN) participam da regulação da dor e podem ter um papel na fisiopatologia das cefaleias peimárias. O objetivo do presente estudo foi avaliar os níveis séricos de FN em pacientes com cefaleia do tipo tensional (CTT). Foi realizado corte transversal com 48 pacientes com CTT e 48 controles pareados por gênero e idade. Os inventários de Beck para depressão e ansiedade, bem como o inventário de impacto da cefaleia foram aplicados. Os níveis séricos de FN foram determinados por ELISA. Não houve diferenças significativas entre níveis de FN entre pacientes com TTH e controles, bem como entre pacientes com TTH episódica e crônica. Presença de cefaleia no momento da avaliação não alterou os níveis séricos de FN. Os escores de depressão, ansiedade e impacto da cefaleia não se correlacionaram com os níveis de FN. Nosso estudo sugere que não há alteração dos níveis de FN na TTH.

Upregulation of blood proBDNF and its receptors in major depression.

BACKGROUND: In recent decades, the role of brain-derived neurotrophic factor (BDNF) in depression has received intensive attention. However, the relationship between proBDNF and depression has not been clearly elucidated. METHODS: Forty drug-free women patients diagnosed with major depression and 50 healthy female controls were enrolled in our study. Peripheral blood was sampled from all the subjects. With the blood samples, we assessed the relationship between BDNF and major depression from following aspects: the levels of BDNF, proBDNF and their receptors in the sera and lymphocytes. The mRNA levels of these factors in lymphocytes were also examined. Furthermore, the correlations between each factor and the severity of major depression were tested. RESULTS: It was found that: (a) the protein and serum levels of proBDNF, sortilin and p75NTR were higher in major depressive patients than in healthy controls while mature BDNF and TrkB levels were lower; (b) the BDNF, TrkB, sortilin and p75NTR mRNA levels changed in line with their protein levels; (c) The levels of mature BDNF and TrkB had negative correlations with the major depression severity, and the levels of proBDNF, p75NTR and sortilin were positively correlated with the scores of HRSD-21; (d) the ratio of proBDNF and mBDNF was imbalanced in major depressive patients. CONCLUSION: The balance between the proBDNF/p75NTR/sortilin and mBDNF/TrkB signaling pathways appears dysregulated in major depression and both pathways should be considered as biomarkers for the major depression LIMITATIONS: More cases on both genders should be enrolled in our study. And further works on the mechanisms of how BDNF and its receptors are regulated in depression should also be carried out.

Neurotrophin serum concentrations and polymorphisms of neurotrophins and their receptors in children with asthma.

BACKGROUND: In the recent years numerous studies have analysed the effects of neurotrophins on allergic inflammation in airway diseases reporting increased neurotrophin levels locally in the airways as well as in serum of asthmatic patients. We aimed to investigate if levels of neurotrophins in serum of asthmatic children are influenced by the genotype of functional variants within genes encoding analysed neurotrophins and their specific receptors. METHODS: In the study we included 98 children diagnosed with asthma. Genotyping of 9 polymorphisms located in neurotrophins genes and their receptors genes was done with use of TaqMan SNP genotyping assays or PCR-RFLP. The serum levels of four neurotrophins (BDNF, NGF, NTF3, NTF4) were analysed during exacerbation of asthma symptoms with use of DuoSet ELISA Development Kit (R&D). RESULTS: The two patients with the genetic variant A/A of NTRK1 (rs6334) showed significantly higher NGF serum concentrations (113.4 and 218.1 pg/mL) as compared to the mean NGF serum concentrations in the total group of patients (34.8 pg/mL). We also observed a significant epistatic interactions between variants of NGF rs6330 and NTRK1 rs6334 that influenced NGF serum level (P = 0.0004). Analysis of four neurotrophins serum levels in relation to different genotypes of analysed neurotrophins genes showed no significant differences among analysed asthmatic children. CONCLUSIONS: Our results suggest that, among analysed neurotrophins, NGF serum levels may be influenced by the genotype of NTRK1 gene individually as well as in the interaction with NGF functional genetic variant suggesting their involvement in allergic inflammation in asthma. Serum levels of the other neurotrophins do not seem to be affected by the variants in the analysed genes.

Immune cell NT-3 expression is associated with brain atrophy in multiple sclerosis patients.

While neurotrophins mediate cell survival and proliferation in the nervous system, they are also expressed within peripheral blood mononuclear cells (PBMCs) of the immunological system. In multiple sclerosis (MS) neurotrophins released from PBMCs might play a neuroprotective role, delaying neurodegeneration within central nervous system. We aimed for identifying the link between neurotrophins' PBMCs expression and brain atrophy markers in relapsing-remitting MS (RRMS) patients. We have found that neurotrophin-3 PBMCs concentration is strongly correlated with brain-parenchymal fraction and corpus callosum cross-sectional area, which are well-established brain atrophy measures. Thus, PBMC-derived neurotrophin-3 might exert a direct or indirect neuroprotective effect in MS.

Serum immune-activation potency and response to anti-TNF-α therapy in Crohn's disease.

AIM: To study whether immune-activation stage in serum of adult Crohn's disease (CD) patients correlates with disease activity and with treatment response to anti-tumor necrosis factor-α (TNF-α) therapy. METHODS: Serum samples were obtained from 15 adult CD patients introduced to anti-TNF-α therapy. The individual stage of immune activation was studied applying our new in vitro assay, in which target cells (donor derived peripheral blood mononuclear cells) were cultured with patient serum and the T-cell activation induced by the patient serum was studied using a panel of markers for effector [interferon γ (IFNγ), interleukin (IL)-5] and regulatory T-cells [forkhead transcription factor 3 (FOXP3) and glucocorticoid-induced tumour necrosis factor receptor (GITR)]. The endoscopic disease activity was assessed with the Crohn's disease endoscopic index of severity (CDEIS) before and 3 mo after therapy with an anti-TNF-α agent. RESULTS: Low induction of FOXP3 and GITR in target cells cultured in the presence of patient serum was associated with high disease activity i.e. CDEIS assessed before therapy (r = -0.621, P = 0.013 and r = -0.625, P = 0.013, respectively). FOXP3 expression correlated inversely with pre-treatment erythrocyte sedimentation rate (r = -0.548, P = 0.034). Low serum induced FOXP3 (r = -0.600, P = 0.018) and GITR (r = -0.589, P = 0.021) expression and low IFNγ secretion from target cells (r = -0.538, P = 0.039) associated with treatment response detected as a decrease in CDEIS. CONCLUSION: The immune-activation potency in the patient serum prior to anti-TNF-α therapy reflected intestinal inflammation and the therapeutic response.