IgM Natural Autoantibodies in Physiology and the Treatment of Disease

Fereidan-Esfahani, Mahboobeh; Nayfeh, Tarek; Warrington, Arthur E.; Howe, Charles L.; Rodriguez, Moses

doi:10.1007/978-1-4939-8958-4_3

Cited by 26 publications

(21 citation statements)

References 152 publications

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“…Natural antibody can be produced in germ-free contexts although its composition is shaped by the microbiota. Natural antibody provides a first line of defense against a range of pathogens and, through opsonization, augments the follicular B cell response (Fereidan-Esfahani et al, 2019;Kearney et al, 2015). The natural antibody also contains antibodies against blood group antigens (Nydegger et al, 2005).…”

Section: Natural Antibody and ''Innate Memory''mentioning

confidence: 99%

“…The natural antibody also contains antibodies against blood group antigens (Nydegger et al, 2005). Natural antibodies against oxidized lipids have a protective role in some atherosclerosis models and may be involved in clearance of apoptotic cells (Fereidan-Esfahani et al, 2019;Sage et al, 2019). Neonatal exposure to microbial antigens that stimulate B1 cells leads to life-long changes in the antibody repertoire that may influence the response to future encounters not only with the same microbe but with a range of other microbes and allergens that share glycan determinants (Kearney et al, 2015).…”

Section: Natural Antibody and ''Innate Memory''mentioning

confidence: 99%

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B Cell Responses: Cell Interaction Dynamics and Decisions

Cyster

Allen

2019

Cell

681

634

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B cells and the antibodies they produce have a deeply penetrating influence on human physiology. Here, we review current understanding of how B cell responses are initiated; the different paths to generate short-and long-lived plasma cells, germinal center cells, and memory cells; and how each path impacts antibody diversity, selectivity, and affinity. We discuss how basic research is informing efforts to generate vaccines that induce broadly neutralizing antibodies against viral pathogens, revealing the special features associated with allergen-reactive IgE responses and uncovering the antibody-independent mechanisms by which B cells contribute to health and disease.

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Section: Natural Antibody and ''Innate Memory''mentioning

confidence: 99%

Section: Natural Antibody and ''Innate Memory''mentioning

confidence: 99%

B Cell Responses: Cell Interaction Dynamics and Decisions

Cyster

Allen

2019

Cell

681

634

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“…At least two possible mechanisms could explain remyelination by Myaptavin-3064 (Figure 5). First, it is possible that Myaptavin-3064 binds to an as-yet unidentified membrane receptor on surviving adult OLs inducing conformational changes in OL cell membranes and activating the extracellular signal-regulated kinase (ERK)1/2 pathway to enhance remyelination by inducing plasticity and the extension of processes into lesions [26]. OLs by reducing activation of caspase-3 and caspase-9 and increasing plasticity by activation of the extracellular signal-regulated kinase (ERK)1/2 pathway.…”

Section: Discussionmentioning

confidence: 99%

Remyelination-Promoting DNA Aptamer Conjugate Myaptavin-3064 Binds to Adult Oligodendrocytes In Vitro

Fereidan-Esfahani

Wilbanks

et al. 2020

Pharmaceuticals

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We previously applied Systematic Evolution of Ligands by EXponential enrichment (SELEX) technology to identify myelin-specific DNA aptamers, using crude mouse central nervous system myelin as bait. This selection identified a 40-nucleotide aptamer (LJM-3064). Multiple biotinylated LJM-3064 molecules were conjugated to a streptavidin core to mimic a multimeric immunoglobulin M (IgM) antibody, generating 3064-BS-streptavidin (Myaptavin-3064). We previously showed that Myaptavin-3064 induces remyelination in the Theiler’s murine encephalomyelitis virus (TMEV) model of chronic spinal cord demyelination. While details of target binding and the mechanism of action remain unclear, we hypothesized that Myaptavin-3064 induces remyelination by binding to oligodendrocytes (OLs). We now report the results of binding assays using the human oligodendroglioma (HOG) cell line, applying both flow cytometry and immunocytochemistry (IC) to assay aptamer conjugate binding to cells. IC assays were applied to compare aptamer conjugate binding to primary embryonic mouse mixed cortical cultures and primary adult rat mixed glial cultures. We show that Myaptavin-3064 binds to HOG cells, with increased binding upon differentiation. In contrast, a negative control aptamer conjugate, 3060-BS, which did not promote central nervous system (CNS) remyelination, does not bind to HOG cells. Myaptavin-3064 did not bind to lung (L2) or kidney (BHK) cell lines. Total internal reflection fluorescence (TIRF) imaging indicates that Myaptavin-3064 binds at the cell membrane of live cells. In addition to HOG cells, Myaptavin-3064 binds to adult rat OLs, but not to embryonic mouse mixed cortical cultures. These data support the hypothesis that Myaptavin-3064 binds to a surface molecule on both rodent and human OLs in a manner that triggers a remyelination signal pathway.

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“…The five isotypes include IgG, IgM, IgA, IgD, and IgE. IgM and IgG in particular are known to fight against infections [9][10]. Autoantibodies are defined as immunoglobulins that attack self-antigens and are a distinguishing factor in autoimmune diseases [9,11].…”

Section: Introductionmentioning

confidence: 99%

The effect of amaranth oil on autoantibodies in lupus prone mice

Martirosyan¹,

Hutcheson²,

Sajitharan³

et al. 2021

Bioactive Compounds in Health and Disease

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Background: Autoimmune diseases, such as systemic lupus erythematosus, can have severe impacts on quality of life. They are one of the leading causes of death for women in the United States. Distinguished by the body damaging its own tissues and organs, they are often classified and diagnosed based on autoantibody levels. Treatments often include immunosuppressant drugs, which can have adverse effects. Aim of Study: Amaranth is a good functional food candidate, possessing antioxidants, bioactive compounds, and a variety of health benefits, such as lowering cholesterol, and aiding diabetes and hypertension. Previous studies have largely focused on the grain or seed, but amaranth oil is less explored. This study examines whether orally administered amaranth oil had any effects on autoantibodies and splenic immune cell populations in murine subjects.Methods: Mice in the experimental group (n = 3) were given 4μl of amaranth oil per gram of mouse weight for 5 days a week over 84 days. Control mice (n = 2) were sham treated on the same schedule with no oil. To determine autoantibody levels, enzyme-linked immunosorbent assays (ELISAs) were first conducted on wells pre-coated with double stranded DNA, single stranded DNA, histones, or double stranded DNA and then histones (nucleosomes). Autoantibody presence was quantified by measuring absorbance at 405nm. Splenic cell populations were examined with flow cytometry and compared using a student’s t-test. Results: Compared to the control group, the mice receiving amaranth oil showed decreased IgG and IgM histone autoantibody absorbance levels throughout the whole study. IgG dsDNA, ssDNA, and nucleosome autoantibody absorbances were lower than that of the control group for the first 42 days. IgM dsDNA, ssDNA, and nucleosome autoantibody absorbances were lower only for the first 14 days. There were no significant differences found amongst splenic immune cell populations between the control and experimental groups.Conclusion: These preliminary data show that amaranth oil may help decrease autoantibody levels in lupus prone murine subjects. However, given the small number of subjects in this study, further research is needed to confirm observed effects and determine the most effective dose and administration schedule. Keywords: autoantibody, IgG, IgM, histone, dsDNA, ssDNA, nucleosome, amaranth oil, immunoglobulin, lupus

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IgM Natural Autoantibodies in Physiology and the Treatment of Disease

Cited by 26 publications

References 152 publications

B Cell Responses: Cell Interaction Dynamics and Decisions

B Cell Responses: Cell Interaction Dynamics and Decisions

Remyelination-Promoting DNA Aptamer Conjugate Myaptavin-3064 Binds to Adult Oligodendrocytes In Vitro

The effect of amaranth oil on autoantibodies in lupus prone mice

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