Human-derived natural antibodies: biomarkers and potential therapeutics

Xu, Xiaohua; Ng, Sher May; Hassouna, Eamonn; Warrington, Arthur E.; Oh, Sang Hyun; Rodriguez, Moses

doi:10.2217/fnl.14.62

Cited by 19 publications

(20 citation statements)

References 108 publications

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“…The IPA titers in both populations ranged from undetectable levels to tens of thousands of units which as noted above is consistent with broad variations in transmitted founder virus IFN-α resistance55358. Possible IPA origins include exposure to unrelated viruses, sensitization to cross reacting antigens, auto-antibodies, low affinity polyreactive antibody and naturally occurring germ line IgG59606162. Regardless of its origins, IPA offers a potential explanation for the means by which IFN-α can provide a barrier to primary HIV infection78963.…”

Section: Discussionsupporting

confidence: 75%

Naturally Occurring Fc-Dependent Antibody From HIV-Seronegative Individuals Promotes HIV-Induced IFN-α Production

Lum

Green

2016

Sci Rep

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A majority of adults without HIV infection and with a low risk of HIV-exposure have plasma IgG antibodies that enhance the rate and magnitude of HIV-induced interferon alpha (IFN-α) production. Fc-dependent IgG-HIV complexes induce IFN-α rapidly and in high titers in response to HIV concentrations that are too low to otherwise stimulate an effective IFN-α response. IFN-α promoting antibody (IPA) counters HIV-specific inhibition of IFN-α production, and compensates for the inherent delay in IFN-α production common to HIV infection and other viruses. Naturally occurring IPA has the potential to initiate a potent IFN-α response early in the course of HIV mucosal invasion in time to terminate infection prior to the creation of a pool of persistently infected cells. The current study adds IPA as a mediator of an Fc-dependent antiviral state capable of preventing HIV infection.

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Section: Discussionsupporting

confidence: 75%

Naturally Occurring Fc-Dependent Antibody From HIV-Seronegative Individuals Promotes HIV-Induced IFN-α Production

Lum

Green

2016

Sci Rep

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“…Natural IgM responses are produced by B1 cells, either B1a or B1b cells, and/or marginal zone B cells (Rothstein et al 2013). B1 cells are a source of IL-10 producing regulatory B cells and play a key role in innate immune responses by producing natural IgM which may suppress inflammation, autoimmune responses, and oxidative stress toxicity, and are a first line defence against invading pathogens (Grönwall and Silverman 2014;Margry et al 2014;Xu et al 2015).…”

Section: Natural Igm Autoimmune Responsesmentioning

confidence: 99%

Increased Autoimmune Responses to Oxidative Specific Epitopes in Bipolar Disorder Type 1 and Major Depression: Towards A Data-Driven, Mechanistic Model of Mood Disorders

Stoyanov¹,

Leunis²,

Murdjeva³

et al. 2020

Preprint

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Major depression is accompanied by increased IgM-mediated autoimmune responses to oxidative specific epitopes (OSEs). Nevertheless, these responses have not been examined in bipolar disorder type 1 (BP1) and BP2. IgM responses to malondialdehyde (MDA), phosphatidinylinositol, oleic acid, and azelaic acid were determined in 35 healthy controls, and 101 mood disorder patients, namely 47 major depressed (MDD), 29 BP1, and 25 BP2 patients. We also measured serum total peroxides, IgG to oxidized LDL (oxLDL), IgM to nitroso-adducts, and IgM/IgA directed to lipopolysaccharides (LPS). IgM responses to OSEs were significantly higher in MDD and BP1 as compared with controls and higher in MDD than in BP2. Partial Least Squares (PLS) analysis showed that 57.7% of the variance in the clinical phenome of mood disorders was explained by number of episodes, IgM directed to OSEs and nitroso-adducts, IgG to oxLDL, and peroxides. There were significant specific indirect effects of IgA/IgM to LPS on the clinical phenome, which were mediated by peroxides, IgM OSEs, and IgG oxLDL. Using PLS we have constructed a data-driven nomothetic network which ensembled causome (increased plasma LPS load), adverse outcome pathways (namely neuro-affective toxicity), and clinical phenome features of mood disorders in a data-driven model. Based on those feature sets, cluster analysis discovered a new diagnostic class characterized by increased plasma LPS load, peroxides, autoimmune responses to OSEs and nitroso-adducts, and increased phenome scores. Using the new nomothetic network approach, we constructed a mechanistically transdiagnostic diagnostic class indicating neuro-affective toxicity in 74.3% of the mood disorder patients.

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“…Natural Abs represent the first line of defense against pathogens; they are usually present in human serum as IgG3, IgM, and IgA and are generated in the absence of previous immune activation ( 44 , 45 ).…”

Section: Mechanism Of Generation Of Anti-self Antibodies (Abs)mentioning

confidence: 99%

“…It has been established that, in human, B cells are able to proliferate and to secrete Abs after exposure to lipopolysaccharide (LPS) from the Gram-negative bacteria membrane independent to the specific B-cell receptor (BCR) ( 48 ). Nevertheless, natural human Abs can also cross-react with microbial antigens, thus allowing host protection to pathogen independent of the previous microbial invasion ( 44 ).…”

Section: Mechanism Of Generation Of Anti-self Antibodies (Abs)mentioning

confidence: 99%

“…The partial differentiation of B-1 cells and their ability to respond rapidly are fundamental for the Abs production to elucidate host protection to pathogens infection via mucosal surfaces and blood. In fact, the production of natural IgM at a steady state by B-1 cells represents a relevant protection against pathogen replication before the development of the antigen-specific response ( 40 , 44 , 45 , 51 , 52 ).…”

Section: Mechanism Of Generation Of Anti-self Antibodies (Abs)mentioning

confidence: 99%

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The Role of Natural Antibodies to CC Chemokine Receptor 5 in HIV Infection

2017

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The CC chemokine receptor 5 (CCR5) is responsible for immune and inflammatory responses by mediation of chemotactic activity in leukocytes, although it is expressed on different cell types. It has been shown to act as co-receptor for the human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV). Natural reactive antibodies (Abs) recognizing first loop (ECL1) of CCR5 have been detected in several pools of immunoglobulins from healthy donors and from several cohorts of either HIV-exposed but uninfected subjects (ESN) or HIV-infected individuals who control disease progression (LTNP) as well. The reason of development of anti-CCR5 Abs in the absence of autoimmune disease is still unknown; however, the presence of these Abs specific for CCR5 or for other immune receptors and mediators probably is related to homeostasis maintenance. The majority of anti-CCR5 Abs is directed to HIV binding site (N-terminus and ECL2) of the receptor. Conversely, it is well known that ECL1 of CCR5 does not bind HIV; thus, the anti-CCR5 Abs directed to ECL1 elicit a long-lasting internalization of CCR5 but not interfere with HIV binding directly; these Abs block HIV infection in either epithelial cells or CD4+ T lymphocytes and the mechanism differs from those ones described for all other CCR5-specific ligands. The Ab-mediated CCR5 internalization allows the formation of a stable signalosome by interaction of CCR5, β-arrestin2 and ERK1 proteins. The signalosome degradation and the subsequent de novo proteins synthesis determine the CCR5 reappearance on the cell membrane with a very long-lasting kinetics (8 days). The use of monoclonal Abs to CCR5 with particular characteristics and mode of action may represent a novel mode to fight viral infection in either vaccinal or therapeutic strategies.

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Human-derived natural antibodies: biomarkers and potential therapeutics

Cited by 19 publications

References 108 publications

Naturally Occurring Fc-Dependent Antibody From HIV-Seronegative Individuals Promotes HIV-Induced IFN-α Production

Naturally Occurring Fc-Dependent Antibody From HIV-Seronegative Individuals Promotes HIV-Induced IFN-α Production

Increased Autoimmune Responses to Oxidative Specific Epitopes in Bipolar Disorder Type 1 and Major Depression: Towards A Data-Driven, Mechanistic Model of Mood Disorders

The Role of Natural Antibodies to CC Chemokine Receptor 5 in HIV Infection

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