Peptide reactivity between multiple sclerosis (MS) CSF IgG and recombinant antibodies generated from clonally expanded plasma cells in MS CSF

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system. The cause of MS is not known completely, and pathology is specified by involved demyelinated areas in the white and gray matter of the brain and spinal cord. Inflammation and peripheral tolerance breakdown due to Treg cell defects and/or effector cell resistance are present at all stages of the disease. Several invading peripheral immune cells are included in the process of the disease such as macrophages, CD8+ T cells, CD4+ T cells, B cells, and plasma cells. Trace elements are known as elements found in soil, plants, and living organisms in small quantities. Some of them (e.g., Al, Cu, Zn, Mn, and Se) are essential for the body’s functions like catalysts in enzyme systems, energy metabolism, etc. Al toxicity and Cu, Zn, and Se toxicity and deficiency can affect the immune system and following neuron inflammation and degeneration. These processes may result in MS pathology. Of course, factors such as lifestyle, environment, and industrialization can affect levels of trace elements in the human body.

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Reduced peripheral blood regulatory B cell levels are not associated with the Expanded Disability Status Scale score in multiple sclerosis

Journal of International Medical Research ◽

10.1177/0300060518783083 ◽

2018 ◽

Vol 46 (9) ◽

pp. 3970-3978 ◽

Cited By ~ 4

Author(s):

Shujun Guo ◽

Qingqing Chen ◽

Xiaoli Liang ◽

Mimi Mu ◽

Jing He ◽

...

Keyword(s):

Multiple Sclerosis ◽

B Cells ◽

Peripheral Blood ◽

Plasma Cells ◽

Serum Levels ◽

Memory B Cells ◽

Healthy Controls ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Edss Score

Objective To investigate levels of regulatory B (Breg) cells, plasma cells, and memory B cells in the peripheral blood, and interleukin (IL)-10 in the serum of multiple sclerosis (MS) patients, and to determine the correlation between Breg cell levels and the Expanded Disability Status Scale (EDSS) score. Methods Levels of Breg cells, plasma cells, and memory B cells in the peripheral blood of 12 MS patients were measured using flow cytometry. IL-10 serum levels were measured by enzyme-linked immunosorbent assay. The correlation between Breg cell levels and MS EDSS score was measured using Pearson’s correlation coefficient. Results Compared with healthy controls, MS patients had decreased levels of CD19+CD24hiCD38hi Breg cells in their peripheral blood and reduced serum levels of IL-10; however, the ratios of CD19+CD27hiCD38hi plasma cells and CD19+CD27+CD24hi memory B cells to total B cells did not differ significantly between healthy controls and MS patients. CD19+CD24hiCD38hi Breg cell levels in the peripheral blood of MS patients were not significantly correlated with MS EDSS score. Conclusion Peripheral blood CD19+CD24hiCD38hi Breg cell levels and serum IL-10 levels were reduced in MS patients compared with controls, but Breg cell levels were not correlated with MS EDSS score.

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Results of Expert Council meeting on modern principles of treatment optimization in patients with relapsing-remitting multiple sclerosis using anti-CD20 monoclonal antibody

Neurology neuropsychiatry Psychosomatics ◽

10.14412/2074-2711-2021-3-131-136 ◽

2021 ◽

Vol 13 (3) ◽

pp. 131-136

Author(s):

A. N. Boyko ◽

N. V. Khachanova ◽

D. S. Korobko ◽

D. S. Kasatkin ◽

Ya. V. Vlasov ◽

...

Keyword(s):

Multiple Sclerosis ◽

Plasma Cells ◽

Risk Groups ◽

Response To Therapy ◽

Treatment Optimization ◽

Correct Treatment ◽

Neuron Damage ◽

Single Standard ◽

Anti Cd20 ◽

Myelin Antigens

The article presents the results of the discussion of the use of anti-B-cell therapy in multiple sclerosis (MS). These cells play a significant role in immunoregulation in MS, not only by producing antibodies to myelin antigens after transformation into plasma cells, but also by presenting the antigen to T cells, producing activation cytokines, and forming laminar follicles. The article provides an expert consensus statement on different drugs of this class in the MS treatment. In addition, the possibilities of determining the disease prognosis for the initially correct treatment choice are highlighted. Undoubtedly, there is a need for confirmation of the MS diagnosis, possible stratification of patients into different risk groups, and evaluation of the response to therapy. Potential additional research methods included evoked potentials and optical coherence tomography, baseline vitamin D3 level as a prognostic marker of the disease course, neurofilament levels in serum and cerebrospinal fluid to confirm neuron damage. However, it takes much time to study, determine the methodology, reference values, and develop a single standard approach to identify and implement a biomarker, which should then be implemented in routine clinical practice.

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Self-reactive and polyreactive B cells are generated and selected in the germinal center during γ-herpesvirus infection

International Immunology ◽

10.1093/intimm/dxz057 ◽

2019 ◽

Vol 32 (1) ◽

pp. 27-38 ◽

Cited By ~ 4

Author(s):

Shuhei Sakakibara ◽

Teruhito Yasui ◽

Hideyuki Jinzai ◽

Kristy O’Donnell ◽

Chao-Yuan Tsai ◽

...

Keyword(s):

B Cells ◽

Immune Responses ◽

Germinal Center ◽

Plasma Cells ◽

Somatic Hypermutation ◽

Recombinant Antibodies ◽

The Self ◽

Herpesvirus Infection ◽

A Minor ◽

Auto Antibody

Abstract Immune responses against certain viruses are accompanied by auto-antibody production although the origin of these infection-associated auto-antibodies is unclear. Here, we report that murine γ-herpesvirus 68 (MHV68)-induced auto-antibodies are derived from polyreactive B cells in the germinal center (GC) through the activity of short-lived plasmablasts. The analysis of recombinant antibodies from MHV68-infected mice revealed that about 40% of IgG+ GC B cells were self-reactive, with about half of them being polyreactive. On the other hand, virion-reactive clones accounted for only a minor proportion of IgG+ GC B cells, half of which also reacted with self-antigens. The self-reactivity of most polyreactive clones was dependent on somatic hypermutation (SHM), but this was dispensable for the reactivity of virus mono-specific clones. Furthermore, both virus-mono-specific and polyreactive clones were selected to differentiate to B220lo CD138+ plasma cells (PCs). However, the representation of GC-derived polyreactive clones was reduced and that of virus-mono-specific clones was markedly increased in terminally differentiated PCs as compared to transient plasmablasts. Collectively, our findings demonstrate that, during acute MHV68 infection, self-reactive B cells are generated through SHM and selected for further differentiation to short-lived plasmablasts but not terminally differentiated PCs.

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A pathogenic and clonally expanded B cell transcriptome in active multiple sclerosis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2008523117 ◽

2020 ◽

Vol 117 (37) ◽

pp. 22932-22943 ◽

Cited By ~ 5

Author(s):

Akshaya Ramesh ◽

Ryan D. Schubert ◽

Ariele L. Greenfield ◽

Ravi Dandekar ◽

Rita Loudermilk ◽

...

Keyword(s):

Multiple Sclerosis ◽

B Cells ◽

B Cell ◽

Single Cell ◽

Rna Sequencing ◽

Chemokine Receptors ◽

Plasma Cells ◽

Cholesterol Biosynthesis ◽

Memory B Cells ◽

Cell Phenotype

Central nervous system B cells have several potential roles in multiple sclerosis (MS): secretors of proinflammatory cytokines and chemokines, presenters of autoantigens to T cells, producers of pathogenic antibodies, and reservoirs for viruses that trigger demyelination. To interrogate these roles, single-cell RNA sequencing (scRNA-Seq) was performed on paired cerebrospinal fluid (CSF) and blood from subjects with relapsing-remitting MS (RRMS; n = 12), other neurologic diseases (ONDs; n = 1), and healthy controls (HCs; n = 3). Single-cell immunoglobulin sequencing (scIg-Seq) was performed on a subset of these subjects and additional RRMS (n = 4), clinically isolated syndrome (n = 2), and OND (n = 2) subjects. Further, paired CSF and blood B cell subsets (RRMS; n = 7) were isolated using fluorescence activated cell sorting for bulk RNA sequencing (RNA-Seq). Independent analyses across technologies demonstrated that nuclear factor kappa B (NF-κB) and cholesterol biosynthesis pathways were activated, and specific cytokine and chemokine receptors were up-regulated in CSF memory B cells. Further, SMAD/TGF-β1 signaling was down-regulated in CSF plasmablasts/plasma cells. Clonally expanded, somatically hypermutated IgM+ and IgG1+ CSF B cells were associated with inflammation, blood–brain barrier breakdown, and intrathecal Ig synthesis. While we identified memory B cells and plasmablast/plasma cells with highly similar Ig heavy-chain sequences across MS subjects, similarities were also identified with ONDs and HCs. No viral transcripts, including from Epstein–Barr virus, were detected. Our findings support the hypothesis that in MS, CSF B cells are driven to an inflammatory and clonally expanded memory and plasmablast/plasma cell phenotype.

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Initial Immunopathogenesis of Multiple Sclerosis: Innate Immune Response

Clinical and Developmental Immunology ◽

10.1155/2013/413465 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 43

Author(s):

Norma Y. Hernández-Pedro ◽

Guillermo Espinosa-Ramirez ◽

Verónica Pérez de la Cruz ◽

Benjamín Pineda ◽

Julio Sotelo

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Plasma Cells ◽

Molecular Mimicry ◽

Innate Immune ◽

Perivascular Spaces ◽

Tissue Destruction ◽

Complex Interactions ◽

The Central Nervous System ◽

Mononuclear Cell Infiltrates

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The hallmark to MS is the demyelinated plaque, which consists of a well-demarcated hypocellular area characterized by the loss of myelin, the formation of astrocytic scars, and the mononuclear cell infiltrates concentrated in perivascular spaces composed of T cells, B lymphocytes, plasma cells, and macrophages. Activation of resident cells initiates an inflammatory cascade, leading to tissue destruction, demyelination, and neurological deficit. The immunological phenomena that lead to the activation of autoreactive T cells to myelin sheath components are the result of multiple and complex interactions between environment and genetic background conferring individual susceptibility. Within the CNS, an increase of TLR expression during MS is observed, even in the absence of any apparent microbial involvement. In the present review, we focus on the role of the innate immune system, the first line of defense of the organism, as promoter and mediator of cross reactions that generate molecular mimicry triggering the inflammatory response through an adaptive cytotoxic response in MS.

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