1,721,033 research outputs found
IgM responses following SARS-CoV-2 vaccination: insights into protective and pre-existing immunity
No full textPeripheral immune reactions following human traumatic spinal cord injury: the interplay of immune activation and suppression
Full text linkTraumatic spinal cord injury (SCI) damages the nerve tissue of the spinal cord, resulting in loss of motor and/or sensory functions at and below the injury level. SCI provokes a long-lasting immune response that extends beyond the spinal cord and induces changes in the composition and function of the peripheral immune system. Seemingly contradictory findings have been observed, as both systemic immune activation, including inflammation and autoimmunity, and immune suppression have been reported. Differences in the levels and functions of various cell types and components of both the innate and adaptive immune system supporting these changes have been described at (sub)acute and chronic stages post-injury. Further research is needed for a more comprehensive understanding of the peripheral immune reactions following SCI, their possible correlations with clinical characteristics, and how these immune responses could be targeted to facilitate the therapeutic management of SCI. In this review, we provide an overview of the current literature discussing changes in the peripheral immune system and their occurrence over time following a traumatic SCI
The macrophage migration inhibitory factor/CD74 axis in traumatic spinal cord injury: lessons learned from animal and human studies
No full textTraumatic spinal cord injury (SCI) is a severe condition leading to long-term impairment of motor, sensory, and autonomic functions. Following the initial injury, a series of additional events is initiated further damaging the spinal cord. During this secondary injury phase, both an inflammatory and immune modulatory response are triggered that have damaging and anti-inflammatory properties, respectively. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) and its receptor CD74 have been extensively studied in traumatic SCI. MIF expression is increased in spinal cord tissue after experimental SCI, mainly in astrocytes and microglia, as well as in the plasma of SCI patients. Functionally, MIF and CD74 were shown to regulate astrocyte viability, proliferation and cholesterol metabolism, microglia migration, and neuronal viability. Moreover, inhibition of the MIF/CD74 axis improved the functional recovery of SCI animals. We provide a detailed overview of studies analyzing the role of MIF and CD74 in traumatic SCI. We describe results from animal studies, using rat and mouse models for SCI, and human studies. Furthermore, we propose a new path for investigation, focused on B cells, that might lead to a better understanding of how MIF and CD74 contribute to the secondary injury cascade following traumatic SCI.This work was supported by Hasselt University, Belgium, and by a grant from the Wings for Life Spinal Cord Research Foundation (WFL-BE-02/22). Figures were created with BioRender.com
IgD−CD27− double negative (DN) B cells: Origins and functions in health and disease
No full textHuman B cells can be divided into four main subsets based on differential expression of immunoglobulin (Ig)D
and CD27. IgD CD27 double negative (DN) B cells make up a heterogeneous group of B cells that have first
been described in relation to aging and systemic lupus erythematosus but have been mostly disregarded in B cell
research. Over the last few years, DN B cells have gained a lot of interest because of their involvement in
autoimmune and infectious diseases. DN B cells can be divided into different subsets that originate via different
developmental processes and have different functional properties. Further research into the origin and function
of different DN subsets is needed to better understand the role of these B cells in normal immune responses and
how they could be targeted in specific pathologies. In this review, we give an overview of both phenotypic and
functional properties of DN B cells and provide insight into the currently proposed origins of DN B cells.
Moreover, their involvement in normal aging and different pathologies is discusseThis work was supported by Hasselt University, Belgium and the Belgian Charcot Foundation. Fig. 1 was created with BioRender.co
Editorial: New Insights Into B Cell Subsets in Health and Disease
No full textTransplantation and immunomodulatio
Identification of spinal cord injury-induced autoantibodies as prognostic biomarkers using serological antigen selection
No full textSpinal cord injury (SCI) is a devastating condition, leading to sensory and motor function loss. SCI disrupts the blood-spinal cord barrier, releasing SCI-related proteins in the blood stream, triggering autoimmune responses and the production of autoantibodies. Since there are no predictive strategies for the SCI-outcome, these SCI-induced autoantibodies can be valuable as prognostic disease markers, especially in patients with worsening of the SCI. Our aim was to identify a full spectrum of SCI-induced autoantibodies from SCI patients’ plasma using serological antigen selection (SAS).
Immunoglobulin (Ig)M and IgG levels in SCI patients’ plasma were determined 0-4 days post-injury (DPI) and 20-33 DPI using ELISA. Next, IgM ELISA and SAS procedures were optimised. SAS used a cDNA phage display library expressing spinal cord proteins, which was screened for SCI-induced autoantibody reactivity using pooled plasma of 12 SCI patients with known worsening of the SCI. Phage expressing antigens to which SCI-induced autoantibodies bound were selected. Selected antigenic targets were characterised using colony PCR and DNA fingerprinting.
SCI patients’ total plasma IgM levels were significantly increased (p=0.0491) 20-33 DPI compared to 0-4 DPI, in contrast, IgG levels remained stable (p=0.3474). SAS and phage ELISA data suggested an increased selection of phage expressing antigens with SCI-induced autoantibody reactivity. DNA fingerprinting of the selected clones identified five digestion patterns, confirming enrichment of phage
Circulating immune profile changes reflect memory immune responses in spinal cord injury patients
No full textFollowing a spinal cord injury (SCI), an inflammatory immune reaction is triggered which results in advanced secondary tissue damage. This study aimed to extensively analyse the circulating immune cell composition in traumatic SCI patients. High-dimensional flow cytometry was performed on peripheral blood mononuclear cells of traumatic SCI patients and healthy controls (n=18 each). SCI blood samples were collected at multiple time points in the (sub)acute ((s)aSCI, 0-4 days and 3 weeks post-SCI) and chronic (cSCI, 6, 12, 18 and >18 weeks post-SCI) disease phase up to a total of 46 SCI samples. Total and CD4 + T cell frequencies were increased in cSCI patients. CD4 + T cells and B cells were shifted towards memory phenotypes in (s)aSCI and cSCI patients, respectively. Most profound changes were observed in the B cell compartment. Decreased immunoglobulin (Ig)G + and increased IgM + B cell frequencies reflected disease severity, as these correlated with American Spinal Injury Association (ASIA) impairment scale (AIS) scores. Post-SCI B cell responses consisted of an increased frequency of B cells and B cell subsets expressing the survival receptor CD74. Expression of CD74 was also elevated on B cell subsets of cSCI but not (s)aSCI patients. In conclusion, post-SCI inflammation is driven by memory immune cell subsets. The elevated CD74 expression on B cells of SCI patients suggests the potential involvement of CD74-related pathways in post-SCI B cell responses. Monitoring of circulating IgM + and IgG + B cell levels could aid in the clinical evaluation and prognosis of SCI patients
Circulating immune profile changes reflect memory immune responses in spinal cord injury patients
No full textFollowing a spinal cord injury (SCI), an inflammatory immune reaction is triggered which results in advanced secondary tissue damage. This study aimed to extensively analyse the circulating immune cell composition in traumatic SCI patients. High-dimensional flow cytometry was performed on peripheral blood mononuclear cells of traumatic SCI patients and healthy controls (n=18 each). SCI blood samples were collected at multiple time points in the (sub)acute ((s)aSCI, 0-4 days and 3 weeks post-SCI) and chronic (cSCI, 6, 12, 18 and >18 weeks post-SCI) disease phase up to a total of 46 SCI samples. Total and CD4 + T cell frequencies were increased in cSCI patients. CD4 + T cells and B cells were shifted towards memory phenotypes in (s)aSCI and cSCI patients, respectively. Most profound changes were observed in the B cell compartment. Decreased immunoglobulin (Ig)G + and increased IgM + B cell frequencies reflected disease severity, as these correlated with American Spinal Injury Association (ASIA) impairment scale (AIS) scores. Post-SCI B cell responses consisted of an increased frequency of B cells and B cell subsets expressing the survival receptor CD74. Expression of CD74 was also elevated on B cell subsets of cSCI but not (s)aSCI patients. In conclusion, post-SCI inflammation is driven by memory immune cell subsets. The elevated CD74 expression on B cells of SCI patients suggests the potential involvement of CD74-related pathways in post-SCI B cell responses. Monitoring of circulating IgM + and IgG + B cell levels could aid in the clinical evaluation and prognosis of SCI patients
IgD-CD27-double negative (DN) B cells of multiple sclerosis patients are mature memory cells that can migrate towards pro-inflammatory chemokines
No full textIgD-CD27-double negative (DN) B cells of multiple sclerosis patients are mature memory cells that can migrate towards pro-inflammatory chemokines
No full text- …
