13 research outputs found
Pro-inflammatory monocyte phenotype and cell-specific steroid signaling alterations in unmedicated patients with major depressive disorder
Several lines of evidence have strongly implicated inflammatory processes in the pathobiology of major depressive disorder (MDD). However, the cellular origin of inflammatory signals and their specificity remain unclear. We examined the phenotype and glucocorticoid signaling in key cell populations of the innate immune system (monocytes) vs. adaptive immunity (T cells) in a sample of 35 well-characterized, antidepressant-free patients with MDD and 35 healthy controls individually matched for age, sex, smoking status and body mass index. Monocyte and T cell phenotype was assessed by flow cytometry. Cell-specific steroid signaling was determined by mRNA expression of pre-receptor regulation (11 beta-hydroxysteroid dehydrogenase type 1; 11 beta-HSD1), steroid receptor expression [glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)], and the downstream target glucocorticoid-induced leucine-zipper (GILZ). We also collected salivary cortisol samples (8:00 a.m. and 10:00 p.m.) on two consecutive days. Patients showed a shift toward a pro-inflammatory phenotype characterized by higher frequency and higher absolute numbers of non-classical monocytes. No group differences were observed in major T cell subset frequencies and phenotype. Correspondingly, gene expression indicative of steroid resistance (i.e., lower expression of GR and GILZ) in patients with MDD was specific to monocytes and not observed in T cells. Monocyte phenotype and steroid receptor expression was not related to cortisol levels or serum levels of IL-6, IL-1 beta, or TNF-alpha. Our results thus suggest that in MDD, cells of the innate and adaptive immune system are differentially affected with shifts in monocyte subsets and lower expression of steroid signaling related genes
Pro-inflammatory monocyte phenotype and cell-specific steroid signaling alterations in unmedicated patients with major depressive disorder
Several lines of evidence have strongly implicated inflammatory processes in the pathobiology of major depressive disorder (MDD). However, the cellular origin of inflammatory signals and their specificity remain unclear. We examined the phenotype and glucocorticoid signaling in key cell populations of the innate immune system (monocytes) vs. adaptive immunity (T cells) in a sample of 35 well-characterized, antidepressant-free patients with MDD and 35 healthy controls individually matched for age, sex, smoking status and body mass index. Monocyte and T cell phenotype was assessed by flow cytometry. Cell-specific steroid signaling was determined by mRNA expression of pre-receptor regulation (11 beta-hydroxysteroid dehydrogenase type 1; 11 beta-HSD1), steroid receptor expression [glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)], and the downstream target glucocorticoid-induced leucine-zipper (GILZ). We also collected salivary cortisol samples (8:00 a.m. and 10:00 p.m.) on two consecutive days. Patients showed a shift toward a pro-inflammatory phenotype characterized by higher frequency and higher absolute numbers of non-classical monocytes. No group differences were observed in major T cell subset frequencies and phenotype. Correspondingly, gene expression indicative of steroid resistance (i.e., lower expression of GR and GILZ) in patients with MDD was specific to monocytes and not observed in T cells. Monocyte phenotype and steroid receptor expression was not related to cortisol levels or serum levels of IL-6, IL-1 beta, or TNF-alpha. Our results thus suggest that in MDD, cells of the innate and adaptive immune system are differentially affected with shifts in monocyte subsets and lower expression of steroid signaling related genes
T Cell Phenotype and T Cell Receptor Repertoire in Patients with Major Depressive Disorder
While a link between inflammation and the development of neuropsychiatric
disorders, including major depressive disorder (MDD) is supported by a growing
body of evidence, little is known about the contribution of aberrant adaptive
immunity in this context. Here, we conducted in-depth characterization of T
cell phenotype and T cell receptor (TCR) repertoire in MDD. For this cross-
sectional caseâcontrol study, we recruited antidepressant-free patients with
MDD without any somatic or psychiatric comorbidities (n = 20), who were
individually matched for sex, age, body mass index, and smoking status to a
non-depressed control subject (n = 20). T cell phenotype and repertoire were
interrogated using a combination of flow cytometry, gene expression analysis,
and next generation sequencing. T cells from MDD patients showed significantly
lower surface expression of the chemokine receptors CXCR3 and CCR6, which are
known to be central to T cell differentiation and trafficking. In addition, we
observed a shift within the CD4+ T cell compartment characterized by a higher
frequency of CD4+CD25highCD127low/â cells and higher FOXP3 mRNA expression in
purified CD4+ T cells obtained from patients with MDD. Finally, flow
cytometry-based TCR VÎČ repertoire analysis indicated a less diverse CD4+ T
cell repertoire in MDD, which was corroborated by next generation sequencing
of the TCR ÎČ chain CDR3 region. Overall, these results suggest that T cell
phenotype and TCR utilization are skewed on several levels in patients with
MDD. Our study identifies putative cellular and molecular signatures of
dysregulated adaptive immunity and reinforces the notion that T cells are a
pathophysiologically relevant cell population in this disorder
Pro-inflammatory Monocyte Phenotype and Cell-Specific Steroid Signaling Alterations in Unmedicated Patients With Major Depressive Disorder
Several lines of evidence have strongly implicated inflammatory processes in the pathobiology of major depressive disorder (MDD). However, the cellular origin of inflammatory signals and their specificity remain unclear. We examined the phenotype and glucocorticoid signaling in key cell populations of the innate immune system (monocytes) vs. adaptive immunity (T cells) in a sample of 35 well-characterized, antidepressant-free patients with MDD and 35 healthy controls individually matched for age, sex, smoking status and body mass index. Monocyte and T cell phenotype was assessed by flow cytometry. Cell-specific steroid signaling was determined by mRNA expression of pre-receptor regulation (11ÎČ-hydroxysteroid dehydrogenase type 1; 11ÎČ -HSD1), steroid receptor expression [glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)], and the downstream target glucocorticoid-induced leucine-zipper (GILZ). We also collected salivary cortisol samples (8:00 a.m. and 10:00 p.m.) on two consecutive days. Patients showed a shift toward a pro-inflammatory phenotype characterized by higher frequency and higher absolute numbers of non-classical monocytes. No group differences were observed in major T cell subset frequencies and phenotype. Correspondingly, gene expression indicative of steroid resistance (i.e., lower expression of GR and GILZ) in patients with MDD was specific to monocytes and not observed in T cells. Monocyte phenotype and steroid receptor expression was not related to cortisol levels or serum levels of IL-6, IL-1ÎČ, or TNF-α. Our results thus suggest that in MDD, cells of the innate and adaptive immune system are differentially affected with shifts in monocyte subsets and lower expression of steroid signaling related genes
An Updated Evaluation of Intrathecal IgG Synthesis Markers in Relation to Oligoclonal Bands
The aim was to evaluate the performance of the latest quantitative marker for intrathecal IgG synthesis and to compare it with other established markers used for the same purpose. We retrospectively applied Auerâs and Reiberâs intrathecal IgG synthesis formulae in a cohort of 372 patients under investigation for central nervous system demyelination who had undergone lumbar puncture and oligoclonal bands (OCBs) detection for demonstrating intrathecal IgG synthesis. A ROC analysis revealed Auerâs formula had lower sensitivity (68%) compared to Reiberâs formula (83%) and IgG index (89%), in our cohort of patients that exhibited normal to mildly elevated albumin quotients (4.48 ± 3.93). By excluding possible sources of errors, we assume that Auerâs formula is less sensitive than other established tools for the âpredictionâ of the detection of OCBs in routine cerebrospinal fluid (CSF) analyses due to the mathematical model used. Given the ability of Reiberâs hyperbolic formula to describe the bloodâCSF IgG distribution across a wide range of bloodâbrain barrier functionality, its use and the use of similar formulae are recommended for the discrimination between CNS-derived and blood-derived molecules in clinical laboratories
Seronegative neurobrucellosis-do we need new neurobrucellosis criteria?
Neurobrucellosis presents in various clinical forms and should always be
considered in neurological pa-tients in highly endemic areas such as the
Mediterranean basin. Establishing a diagnosis can be challeng-ing since
serological testing can sometimes yield negative results. We present a
rare case of a seroneg-ative relapse of neurobrucellosis in a patient
who had been successfully treated for systemic brucellosis. Oligoclonal
bands, an agglutination test, and 16S rRNA sequencing of cerebrospinal
fluid proved essential in unmasking a confined central nervous system
relapse. This case reinforces the need for establishing diagnostic
criteria for neurobrucellosis, which could potentially include
oligoclonal bands and an aggluti-nation test on the cerebrospinal fluid.
(c) 2021 The Authors. Published by Elsevier Ltd on behalf of
International Society for Infectious Diseases. This is an open access
article under the CC BY-NC-ND license (
http://creativecommons.org/licenses/by-nc-nd/4.0/
Diagnostic accuracy for major depression in multiple sclerosis using self-report questionnaires
Objective Multiple sclerosis and major depressive disorder frequently co-occur
but depression often remains undiagnosed in this population. Self-rated
depression questionnaires are a good option where clinician-based standardized
diagnostics are not feasible. However, there is a paucity of data on
diagnostic accuracy of self-report measures for depression in multiple
sclerosis (MS). Moreover, head-to-head comparisons of common questionnaires
are largely lacking. This could be particularly relevant for high-risk
patients with depressive symptoms. Here, we compare the diagnostic accuracy of
the Beck Depression Inventory (BDI) and 30-item version of the Inventory of
Depressive Symptomatology Self-Rated (IDS-SR30) for major depressive disorder
(MSS) against diagnosis by a structured clinical interview. Methods Patients
reporting depressive symptoms completed the BDI, the IDS-SR30 and underwent
diagnostic assessment (Mini International Neuropsychiatric Interview,
M.I.N.I.). Receiver-Operating Characteristic analyses were performed,
providing error estimates and false-positive/negative rates of suggested
thresholds. Results Data from n = 31 MS patients were available. BDI and IDS-
SR30 total score were significantly correlated (r = 0.82). The IDS-SR30total
score, cognitive subscore, and BDI showed excellent to good accuracy (area
under the curve (AUC) 0.86, 0.91, and 0.85, respectively). Conclusion Both the
IDS-SR30 and the BDI are useful to quantify depressive symptoms showing good
sensitivity and specificity. The IDS-SR30 cognitive subscale may be useful as
a screening tool and to quantify affective/cognitive depressive
symptomatology
Initial Data and a Clinical Diagnosis Transition for the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) Study
Background and Objectives: This article presents data from the ongoing Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study (ALBION) regarding baseline clinical characterizations and CSF biomarker profiles, as well as preliminary longitudinal data on clinical progression. Materials and Methods: As of March 2022, 138 participants who either were cognitively normal (CN, n = 99) or had a diagnosis of mild cognitive impairment (MCI, n = 39) had been recruited at the specialist cognitive disorders outpatient clinic at Aiginition Hospital. Clinical characteristics at baseline were provided. These patients were followed annually to determine progression from CN to MCI or even dementia. CSF biomarker data (amyloid β1-42, phosphorylated tau at threonine 181, and total tau) collected using automated Elecsys® assays (Roche Diagnostics) were available for 74 patients. These patients were further sorted based on the AT(N) classification model, as determined by CSF Aβ42 (A), CSF pTau (T), and CSF tTau (N). Results: Of the 49 CN patients with CSF biomarker data, 21 (43%) were classified as exhibiting “Alzheimer’s pathologic change” (A+Τ– (Ν)−) and 6 (12%) as having “Alzheimer’s disease” (A+T–(N)+, A+T+(N)–, or A+T+(N)+). Of the 25 MCI patients, 8 (32%) displayed “Alzheimer’s pathologic change”, and 6 (24%) had “Alzheimer’s disease”. A total of 66 individuals had a mean follow-up of 2.1 years (SD = 0.9, min = 0.8, max = 3.9), and 15 of those individuals (22%) showed a clinical progression (defined as a worsening clinical classification, i.e., from CN to MCI or dementia or from MCI to dementia). Overall, participants with the “AD continuum” AT(N) biomarker profile (i.e., A+T–(N)–, A+T–(N)+, A+T+(N)–, and A+T+(N)+) were more likely to clinically progress (p = 0.04). Conclusions: A CSF “AD continuum” AT(N) biomarker profile is associated with an increased risk of future clinical decline in CN or MCI subjects
Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform
International audienceL-Dopa decarboxylase ( DDC ) is the most significantly co-expressed gene with ACE2 , which encodes for the SARS-CoV-2 receptor a ngiotensin- c onverting e nzyme 2 and the interferon-inducible truncated isoform dACE2 . Our group previously showed the importance of DDC in viral infections. We hereby aimed to investigate DDC expression in COVID-19 patients and cultured SARS-CoV-2-infected cells, also in association with ACE2 and dACE2 . We concurrently evaluated the expression of the viral infection- and interferon-stimulated gene ISG56 and the immune-modulatory, hypoxia-regulated gene EPO . Viral load and mRNA levels of DDC , ACE2 , dACE2 , ISG56 and EPO were quantified by RT-qPCR in nasopharyngeal swab samples from COVID-19 patients, showing no or mild symptoms, and from non-infected individuals. Samples from influenza-infected patients were analyzed in comparison. SARS-CoV-2-mediated effects in host gene expression were validated in cultured virus-permissive epithelial cells. We found substantially higher gene expression of DDC in COVID-19 patients (7.6-fold; p = 1.2e-13) but not in influenza-infected ones, compared to non-infected subjects. dACE2 was more elevated (2.9-fold; p = 1.02e-16) than ACE2 (1.7-fold; p = 0.0005) in SARS-CoV-2-infected individuals. ISG56 (2.5-fold; p = 3.01e-6) and EPO (2.6-fold; p = 2.1e-13) were also increased. Detected differences were not attributed to enrichment of specific cell populations in nasopharyngeal tissue. While SARS-CoV-2 virus load was positively associated with ACE2 expression (râ„0.8, p<0.001), it negatively correlated with DDC , dACE2 (râ€â0.7, p<0.001) and EPO (râ€â0.5, p<0.05). Moreover, a statistically significant correlation between DDC and dACE2 expression was observed in nasopharyngeal swab and whole blood samples of both COVID-19 and non-infected individuals (râ„0.7). In VeroE6 cells, SARS-CoV-2 negatively affected DDC , ACE2 , dACE2 and EPO mRNA levels, and induced cell death, while ISG56 was enhanced at early hours post-infection. Thus, the regulation of DDC , dACE2 and EPO expression in the SARS-CoV-2-infected nasopharyngeal tissue is possibly related with an orchestrated antiviral response of the infected host as the virus suppresses these genes to favor its propagation
Impact of Age and Sex on Antibody Response Following the Second Dose of COVID-19 BNT162b2 mRNA Vaccine in Greek Healthcare Workers
International audienceAnti-SARS-CoV-2 spike RBD (receptor-binding domain) IgG antibody levels were monitored in 1643 volunteer healthcare workers of Eginition, Evangelismos, and Konstantopoulio General Hospitals (Athens, Greece), who underwent vaccination with two doses of COVID-19 BNT162b2 mRNA vaccine (Pfizer) and had no history of SARS-CoV-2 infection. Venous blood was collected 20â30 days after the second vaccine dose and anti-RBD IgG levels were determined using CMIA SARS-CoV-2 IgG II Quant (Abbott) on ARCHITECT i System or ADVIA Centaur SARS-CoV-2 IgG (Siemens) on Centaur XP platform. From the total population of 1643 vaccinees (533 M/1110 F; median age = 49; interquartile range-IQR = 40â56), 1636 (99.6%) had anti-SARS-CoV-2 IgG titers above the positivity threshold of the assay used. One-Way ANOVA Kruskal-Wallis H test showed a statistically significant difference in the median of antibody titers between the different age groups (p < 0.0001). Consistently, Spearmanâs correlation coefficient (r) for IgGs and age as continuous variables was â0.2380 (p = 1.98 Ă 10â17). Moreover, antibody titers were slightly higher by 1.2-mean fold (p = 3 Ă 10â6) in the total female population of the three hospitals (median = 1594; IQR = 875â2584) as compared to males (median = 1292; IQR = 671.9â2188). The present study supports that BNT162b2 vaccine is particularly effective in producing high anti-SARS-CoV-2 IgG levels in healthy individuals, and this humoral response is age- and gender-dependent