Mesangial Cell-Specific Antibodies Are Central to the Pathogenesis of Lupus Nephritis

Not only is nephritis a common complaint in systemic lupus erythematosus, but it is also the most life-threatening complication of the disease. Anti-double-stranded DNA antibodies (Abs), which are found in up to 80% of these patients, might be nephritogenic per se. That is, they may cross-react with mesangial cell (MC) surface proteins, such as alpha-actinin and annexin A2, they may cross-react with mesangial matrix protein such as laminine and fibronectin, or they may recognize chromatin material previously deposited in the glomeruli. The consequence of the binding of anti-MC Abs may be their internalization, which results in activation and proliferation of these MCs. In turn, these activated MCs are suspected of promoting immune complex formation by sequestering and thereby protecting chromatin from degradation. The present paper will explain the mechanisms through which such autoAbs may initiate nephritis

Exploring with [18F]UCB-H the in vivo cariations in SV2A expression through the kainic acid rat model of temporal lobe epilepsy

Purpose The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model. Procedures Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n = 5) or kainic acid (5 mg/kg/injection, epileptic group, n = 15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [F-18]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed. Results Control rats presented a significant increase in [F-18]UCB-H binding at the last two scans, compared with the first ones (p < 0.001). This increase existed but was lower in epileptic animals, producing significant group differences in all the phases of the disease (p < 0.028). Furthermore, the quantification of the SV2A expression in vivo with the [F-18]UCB-H radiotracer or ex vivo with immunofluorescence led to equivalent results, with a positive correlation between both. Conclusions Even if further studies in humans are required, the ability to detect a progressive decrease in SV2A expression during the development of temporal lobe epilepsy supports the use of [F-18]UCB-H as a useful tool to differentiate, in vivo, between healthy and epileptic animals along with the development of the epileptic disease

In vivo exploration of synaptic projections in frontotemporal dementia.

The purpose of this exploratory research is to provide data on synaptopathy in the behavioral variant of frontotemporal dementia (bvFTD). Twelve patients with probable bvFTD were compared to 12 control participants and 12 patients with Alzheimer’s disease (AD). Loss of synaptic projections was assessed with ­[18F]UCBH-PET. Total distribution volume was obtained with Logan method using carotid artery derived input function. Neuroimages were analyzed with SPM12. Verbal fluency, episodic memory and awareness of cognitive impairment were equally impaired in patients groups. Compared to controls, ­[18F]UCBH uptake tended to decrease in the right anterior parahippocampal gyrus of bvFTD patients. Loss of synaptic projections was observed in the right hippocampus of AD participants, but there was no significant difference in ­[18F]UCBH brain uptake between patients groups. Anosognosia for clinical disorder was correlated with synaptic density in the caudate nucleus and the anteromedial prefrontal cortex. This study suggests that synaptopathy in bvFTD targets the temporal social brain and self-referential processes

In vivo imaging of synaptic loss in Alzheimer’s disease with [18F]UCB-H Positron Emission Tomography

IUAP - Interuniversity Attraction Poles Programme (IUAP 7/11); ARC - Actions de recherche concertées (ARC 12/17-01); Special Research Funds classical grant 2016 (Faculty of Medicine, University of Liege, Belgium), FRS-FNR

Homozygous FCGR3A-158F mutation is associated with delayed B-cell depletion following rituximab but with preserved efficacy in a patient with refractory lupus nephri

International audienceRituximab (RTX), an anti-CD20 monoclonal antibody, has shown promising results in a small group of systemic lupus erythematosus (SLE) patients treated for lupus nephritis (LN). However, such observations were not confirmed in the double-blind LUNAR study. Accordingly, the factors associated with the clinical response remain to be characterized. We report the case of a young woman with known LN successfully re-treated with RTX and steroids and homozygous for the low-affinity FCG3RA 158F genotype. Although B-cell depletion was delayed, complete remission with anti-DNA antibody negativity and proteinuria normalization were maintained for 5 years. The implications for disease pathogenesis and clinical monitoring are discussed

Human embryonic kidney cell surface binding characterize patients with active lupus nephritis

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Therapeutic plasma exchange and anti-glomerular basement membrane autoantibodies in Goodpasture syndrome

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Human embryonic kidney cell surface binding characterize patients with active lupus nephritis

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[18F]FMT: a reliable PET tracer for in vivo evaluation of dopaminergic dysfunction in Parkinson’s Disease rat model.

Background: Rat models of Parkinson’s disease (PD), such as lesioned rats with 6-hydroxydopamine (6-OHDA), are useful for studying dopamine (DA)-related functions. 6-[18F]fluoro-m-tyrosine (6-[18F]FMT) is an effective PET tracer to evaluate of DA terminals integrity and L-aromatic amino acid decarboxylase (AAAD) metabolic pathway. However, there are currently no available quantitative PET studies using [18F]FMT in 6-OHDA lesioned rats. In this context, we investigated the feasibility of in vivo PET study using [18F]FMT on 6-OHDA PD’s model. Methods: 10 µg of 6-OHDA were injected into the right medial forebrain bundle (MFB) of male Sprague-Dawley rats (n=8). As control, sham-treated rats (n=8) were injected with vehicle only but otherwise treated identically. Striatal DA presynaptic activity was assessed by dynamic [18F]FMT PET, 30 min after benserazide pretreatment. Structural T2-weighted brain images were acquired on a 9.4T MRI and were used for co-registration. After normalization on a MRI template, kinetic analysis was performed by “Patlak Reference” model, using PMOD software. Results: Striatal accumulation of [18F]FMT was observed in rats pretreated with benserazide, a peripheral AAAD inhibitor. As consequence of the 6-OHDA-lesion, significant decrease of [18F]FMT accumulation was recorded in the striatum ipsilateral to the lesion. Lesioned rats had dramatically reduced uptake constant Ki in the ipsilateral striatum compared to the contralateral striatum (p<0.001) and to the ipsilateral striatum of sham-treated rats (p<0.005). The Ki ratio (Ipsi./Contra.) was equivalent to 94% in the sham group and dropped to 41% in the lesioned group. Conclusions: [18F]FMT PET enables us to quantify loss of DA presynaptic function in unilaterally 6-OHDA lesioned rats. These results encourage us to pursue further investigations in a longitudinal way and to monitor the progression of the dopaminergic dysfunction in more moderate and gradual preclinical PD models