Intracellular IL-10 detection in T cells by flowcytometry: the use of protein transport inhibitors revisited.

In the past two decades, interleukin-10 (IL-10) has gained much attention as an important regulatory cytokine involved in self-tolerance. Functional assessment of IL-10 producing immune cells is traditionally done by stimulation and measurement of cytokine production by flowcytometry. Thereby a protein transport inhibitor like monensin is used to accumulate the cytokine of interest intracellularly.

Resting-state fMRI as a biomarker for Alzheimer's disease?

Previous work indicates that resting-state functional magnetic resonance imaging (fMRI) is sensitive to functional brain changes related to Alzheimer's disease (AD) pathology across the clinical spectrum. Cross-sectional studies have found functional connectivity differences in the brain's default mode network in aging, mild cognitive impairment, and AD. In addition, two recent longitudinal studies have shown that functional connectivity changes track AD progression.

Gastrointestinal-associated autoantibodies in different autoimmune diseases.

Background: Gastrointestinal (GI)-related autoantibodies (Abs) are rarely evaluated in autoimmune diseases (AID) other than inflammatory bowel disease, autoimmune hepatitis and celiac disease. Our aim was to determine the prevalence of these antibodies in a wide spectrum of AID.

Methods: We examined 923 serum samples representing 18 AID and compared them with 338 samples from healthy subjects.

Genetic polymorphisms and surface expression of CTLA-4 and PD-1 on T cells of silica-exposed workers.

Exposure to silica dust has been examined as a possible risk factor for autoimmune diseases, including scleroderma, rheumatoid arthritis and systemic lupus erythematosus. Since CTLA-4 [CD152] and PD-1 [CD279] are important for the maintenance of peripheral tolerance by regulating T cell responsiveness, we evaluated the expression of these molecules on the surface of CD4 and CD8 T cells, as well as single nucleotide polymorphisms (SNP) in CTLA-4 and PDCD1 genes, of 70 silica-exposed workers and 30 non-exposed, age-, ethnically- and sex-matched controls. Expression of CTLA-4 was significantly (P<0.

Th17 expansion in MS patients is counterbalanced by an expanded CD39+ regulatory T cell population during remission but not during relapse.

In this study, percentages of CD39(+) Treg and Th17 cells were compared between relapsing-remitting MS patients and controls and were related to the vitamin D status. The Th17 cell population was expanded in about 40% of the MS patients. In MS patients in remission, but not during relapse, a positive association was found between Th17 cell and CD39(+) Treg percentages (r=0.

Angiogenic T-cells and putative endothelial progenitor cells in hypertension-related cerebral small vessel disease.

Background And Purpose: Cerebral small vessel disease (CSVD) may be caused by endothelial dysfunction, whereas endothelial progenitor cells (EPC) may attenuate endothelial dysfunction. Their vitality is lower in CSVD. A subset of lymphocytes, angiogenic T-cells, is capable to stimulate EPC function.

Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naïve/memory Breg ratio during a relapse but not in remission.

In this study, we assessed B cell subsets, including Bregs, during stable and active disease in relapsing remitting multiple sclerosis (RRMS) patients and related B cell subsets to vitamin D status. We report that RRMS patients have a decreased percentage of both memory B cells and Bregs compared to healthy controls. During a relapse, the reduction in Bregs involved in particular naïve Bregs.

Vitamin D in the healthy and inflamed central nervous system: access and function.

High exposure to vitamin D may protect against development and progression of multiple sclerosis (MS), possibly through the immunomodulatory properties of its biologically active metabolite 1,25-dihydroxyvitamin D. So far, most studies on the possible mechanisms for vitamin D involvement in MS have focused on immune modulation outside the central nervous system (CNS). However, vitamin D may also interfere with the pathophysiology of MS within the CNS.

Resting-state fMRI changes in Alzheimer's disease and mild cognitive impairment.

Regional functional connectivity (FC) of 39 patients with Alzheimer's disease (AD), 23 patients with mild cognitive impairment (MCI), and 43 healthy elderly controls was studied using resting-state functional magnetic resonance imaging (rs-fMRI). After a mean follow-up of 2.8 ± 1.

Functional connectivity tracks clinical deterioration in Alzheimer's disease.

While resting state functional connectivity has been shown to decrease in patients with mild and/or moderate Alzheimer's disease, it is not yet known how functional connectivity changes in patients as the disease progresses. Furthermore, it has been noted that the default mode network is not as homogenous as previously assumed and several fractionations of the network have been proposed. Here, we separately investigated the modulation of 3 default mode subnetworks, as identified with group independent component analysis, by comparing Alzheimer's disease patients to healthy controls and by assessing connectivity changes over time.

Neutrophils and T cells: bidirectional effects and functional interferences.

Polymorphonuclear cells (PMN) are widely recognized as sophisticated killers during microbial infections. In recent years, PMN have been shown to interact and functionally interfere with other cells of the immune system. In this study, we investigated PMN-T cell interactions in an in vitro co-culture system.

Effect of vitamin D(3) supplementation on peripheral B cell differentiation and isotype switching in patients with multiple sclerosis.

Background: Vitamin D has been proposed as a promoter of immune homeostasis in multiple sclerosis (MS). During the past decade, the focus of the effects of vitamin D has been on dendritic cells and on T cells. Since there is an increasing interest in the role of B cells in the pathophysiology of MS, we studied the role of vitamin D on B cells in vivo in patients with MS.

Infectious serologies and autoantibodies in hepatitis C and autoimmune disease-associated mixed cryoglobulinemia.

Mixed cryoglobulinemia (MC) syndrome is an immune complex-mediated vasculitis characterized by the clinical triad of purpura, weakness, and arthralgias, the morbidity of which is mainly related to kidney and peripheral nervous system dysfunction as well as to the development of a secondary lymphoma (Ferri et al. Autoimmun Rev 7:114-120, 2007, Lidar et al. Ann N Y Acad Sci 1173:649-657, 2009, Trejo et al.

Effects of vitamin D on the peripheral adaptive immune system: a review.

Epidemiological studies have shown that a poor vitamin D status is associated with an increased risk of several diseases, including autoimmune diseases. The immune regulatory function of vitamin D is thought to have an important role in these associations. Cells of the adaptive immune system have shown to be direct targets of the vitamin D metabolites.

Vascular inflammation in cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is considered to be caused by an increased permeability of the blood-brain barrier and results in enlargement of Virchow Robin spaces (VRs), white matter lesions, brain microbleeds, and lacunar infarcts. The increased permeability of the blood-brain barrier may relate to endothelial cell activation and activated monocytes/macrophages. Therefore, we hypothesized that plasma markers of endothelial activation (adhesion molecules) and monocyte/macrophage activation (neopterin) relate to CSVD manifestations.

Performance evaluation of a novel chemiluminescence assay for detection of anti-GBM antibodies: an international multicenter study.

Background: Autoantibodies to the non-collagen region (NC1) of the alpha-3 subunit of collagen IV represent a serological hallmark in the diagnosis of Goodpasture's syndrome (GPS). The objective of our study was to carefully analyze the performance characteristics of a novel anti-glomerular basement membrane (GBM) chemiluminescence immunoassay (CIA).

Methods: Sera from patients with GPS (n = 90) were collected from four clinical centers.

Vitamin D-related gene expression profiles in immune cells of patients with relapsing remitting multiple sclerosis.

An impaired vitamin D (vit-D) processing by immune cells of relapsing remitting multiple sclerosis (RRMS) patients may increase their vulnerability for a poor vit-D status. We assessed with qPCR the expression of vit-D related genes in PBMC and CD4+ T-cells. Gene expression profiles of vit-D receptor (VDR), CYP27B1 and CYP24A1 did not differ between RRMS patients and healthy controls.

Vitamin D as a T-cell modulator in multiple sclerosis.

Vitamin D is a potent immune modulator, keeping the T-cell compartment in a more tolerogenic state. Multiple sclerosis (MS), a disease in which an autoreactive T-cell response contributes to inflammation in the central nervous system, has been associated with vitamin D deficiency. The effects of vitamin D on the immune system are believed to be an important driver of this association.

Abdominal fat mass is associated with adaptive immune activation: the CODAM Study.

Abdominal fat-related activation of the innate immune system and insulin resistance (IR) are implicated in the pathogenesis of cardiovascular diseases. Recent data support an important role of the adaptive immune system as well. In this study, we investigate the association between waist circumference and markers of systemic adaptive immune activation, and the potential mediating role of innate immune activation and/or IR herein.

Geographical differences in autoantibodies and anti-infectious agents antibodies among healthy adults.

Much is known about the geoepidemiology of defined autoimmune diseases (AD); however, there is currently limited data regarding the prevalence of autoantibodies among healthy populations of different geographical areas. The aim of this study was to evaluate a large profile of autoantibodies in healthy adults from distinct global regions as well as the prevalence of anti-infectious agents antibodies in those regions. Sera samples from 557 healthy donors were obtained at six centers located in different countries (i.

Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis.

Background: A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures.

Loss of 'small-world' networks in Alzheimer's disease: graph analysis of FMRI resting-state functional connectivity.

Background: Local network connectivity disruptions in Alzheimer's disease patients have been found using graph analysis in BOLD fMRI. Other studies using MEG and cortical thickness measures, however, show more global long distance connectivity changes, both in functional and structural imaging data. The form and role of functional connectivity changes thus remains ambiguous.

Autoantibodies against oxidized low-density lipoprotein in cerebral small vessel disease.

Background And Purpose: Oxidized low-density lipoprotein (oxLDL) induces endothelial dysfunction and antibody formation. Because endothelial dysfunction is involved in cerebral small vessel disease (CSVD) (dilated Virchow Robin spaces, lacunar infarcts, and white matter lesions), oxLDL antibodies could play a role in CSVD pathogenesis. Therefore, we studied oxLDL antibodies in patients with high prevalence of CSVD: lacunar stroke patients and essential hypertensive patients.