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Gut-educated IgA plasma cells defend the meningeal venous sinuses.

ABSTRACT: The central nervous system has historically been viewed as an immune-privileged site, but recent data have shown that the meninges-the membranes that surround the brain and spinal cord-contain a diverse population of immune cells¹. So far, studies have focused on macrophages and T cells, but have not included a detailed analysis of meningeal humoral immunity. Here we show that, during homeostasis, the mouse and human meninges contain IgA-secreting plasma cells. These cells are positioned adjacent to dural venous sinuses: regions of slow blood flow with fenestrations that can potentially permit blood-borne pathogens to access the brain². Peri-sinus IgA plasma cells increased with age and following a breach of the intestinal barrier. Conversely, they were scarce in germ-free mice, but their presence was restored by gut re-colonization. B cell receptor sequencing confirmed that meningeal IgA⁺ cells originated in the intestine. Specific depletion of meningeal plasma cells or IgA deficiency resulted in reduced fungal entrapment in the peri-sinus region and increased spread into the brain following intravenous challenge, showing that meningeal IgA is essential for defending the central nervous system at this vulnerable venous barrier surface.

SUBMITTER: Fitzpatrick Z

PROVIDER: S-EPMC7748383 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Gut-educated IgA plasma cells defend the meningeal venous sinuses.

Fitzpatrick Zachary Z Frazer Gordon G Ferro Ashley A Clare Simon S Bouladoux Nicolas N Ferdinand John J Tuong Zewen Kelvin ZK Negro-Demontel Maria Luciana ML Kumar Nitin N Suchanek Ondrej O Tajsic Tamara T Harcourt Katherine K Scott Kirsten K Bashford-Rogers Rachel R Helmy Adel A Reich Daniel S DS Belkaid Yasmine Y Lawley Trevor D TD McGavern Dorian B DB Clatworthy Menna R MR

Nature 20201104 7834

The central nervous system has historically been viewed as an immune-privileged site, but recent data have shown that the meninges-the membranes that surround the brain and spinal cord-contain a diverse population of immune cells<sup>1</sup>. So far, studies have focused on macrophages and T cells, but have not included a detailed analysis of meningeal humoral immunity. Here we show that, during homeostasis, the mouse and human meninges contain IgA-secreting plasma cells. These cells are positio ...[more]

PMID: 33149302

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Project description:PurposeTo evaluate the alteration of pressure characteristics in the cerebral venous sinuses before and after venous sinus stenting (VSS) using mean sinus pressures (MSPs), sinus pressure gradient (SPG), and sinus pressure pulsatility (SPP) parameters among the idiopathic intracranial hypertension (IIH) patients.Materials and methodsProspective evaluation of 45 consecutive IIH patients who underwent VSS at our institution. A written informed consent approved by the Weill Cornell Institutional Review Board was signed by the study participants. All patients (n = 45) were evaluated for MSPs and SPG. In a subgroup of 12 (n = 12) consecutive patients, SPP was measured. MSP was measured using microcatheter at superior sagittal sinus (SSS), transverse sinus (TS), and sigmoid sinus (SS). SPG was measured as trans-stenotic gradient and trans-torcular gradient. SPP was recorded in the dominant TS with a six French intermediate catheter. Statistical analysis was performed using paired student t-test and two sample t-tests tested for both equal and unequal variances. P values below 0.05 were considered significant.ResultsThe mean age of the study population was 30.6 ± 10 years (7-59 years) and 43 out of 45 are female patients. The mean weight and BMI of the study population were 96 ± 24.7 kg (30.8-144 kg) and 35.6 ± 8.3 kg/M2 (16.4-51.4 kg/M2), respectively. VSS in IIH patients resulted in immediate reduction of MSP in the SSS {Δ Mean: -8.1 mm Hg [95% confidence interval (CI): -5.0-11.7 mm Hg], p < 0.001} and TS [Δ Mean: -11.8 mm Hg (95% CI: -7.5 to 13.4 mm Hg), p < 0.001] and increase of MSP in SS [Δ Mean: 7.5 mm Hg (95% CI: 6-10.1 mm Hg), p < 0.001]. Significant reduction of trans-stenotic SPG reduction [Δ Mean: -15.7 mm Hg (95% CI: -13.6-17.8 mm Hg), p < 0.001] and SPP [Δ Mean: -8 mm Hg (95% CI: -2.5-13.4 mm Hg), p < 0.05] was observed following VSS.ConclusionVSS resulted in immediate alteration of the cerebral venous sinus pressure measurements in patients with IIH.

Project description:PurposeMagnetic resonance venography (MRV) has not been validated in pre-operative planning of the dural venous sinus stenting (VSS) among idiopathic intracranial hypertension (IIH) patients. We aim to prospectively evaluate dural venous sinus measurement in IIH patient population on two-dimensional time-of-flight (2D-TOF) MRV and Three-dimensional contrast-enhanced (3D-CE) MRV acquisitions and compare them against real-time endoluminal measurements with intravascular ultrasound (IVUS), served as the reference.Materials and methodsThe study has been approved by the Weill Cornell Medicine institutional review board. All patients signed written informed consent approved by IRB. Prospective evaluation of forty-five consecutive IIH patients treated with VSS at our institution were evaluated. Patients with pre-stent magnetic resonance venography (MRV) ≤ 6-months of VSS and intravascular ultrasound (IVUS) during VSS constituted the study population. Maximum diameter (in mm), Area (in cm2) and Perimeter (in cm) were measured at posterior 1/3rd of superior sagittal sinus (SSS), proximal transverse sinus (PTS), proximal sigmoid sinus (PSS) and mid sigmoid sinus (MSS) on 2D-TOF-MRV, 3D-CE-MRV and IVUS. Statistical analysis performed using box and whisker plots, Bland-Altman analysis and paired sample t-test.ResultsTwenty (n = 20) patients constituted our study population. The mean age was 30±11 years (7-59 years) and 18 out of 20 were female patients. Mean weight and BMI (range) were 86.3±18.3 kilograms (30.8-107.5 kgs) and 32.9±6.8 kg/M2 (16.4-48.3kg/M2) respectively. The CE-MRV significantly oversized the cerebral venous sinuses compared to TOF-MRV (Dmax: +2.0±1.35 mm, p<0.001; Area: +13.31±10.92 mm2, p<0.001 and Perimeter: +4.79±3.4 mm, p<0.001) and IVUS (Dmax: +1.52±2.16 mm, p<0.001; Area: +10.03±21.5 mm2, p<0.001 and Perimeter: +4.15±3.27 mm, p<0.001). The TOF-MRV sinus measurements were in good agreement with the IVUS measurements with no significant variation (Dmax: +.21±2.23 mm, p = 0.49; Area: +2.51±20.41mm2, p = 0.347 and Perimeter: +.001±1.11 mm, p = 0.991).ConclusionWe report baseline cerebral venous sinus measurements (maximum diameter, area and perimeter) in patients with idiopathic intracranial hypertension. In our experience, TOF-MRV is a reliable representation of endoluminal cerebral venous sinus dimensions, and CE-MRV measurements reflected an overestimation of the endoluminal sinus dimensions when compared against the real time IVUS measurements.

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Gut-educated IgA plasma cells defend the meningeal venous sinuses.

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Gut-educated IgA plasma cells defend the meningeal venous sinuses.

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