The protective effect of modified intravenous immunoglobulin in LPS sepsis model is associated with an increased IRA B cells response

Djoumerska-Alexieva, Iglika; Pashova, Shina; Vassilev, Tchavdar; Pashov, Anastas

doi:10.1016/j.autrev.2012.10.010

Cited by 13 publications

(9 citation statements)

References 19 publications

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“…tain B cells are thought to play a role in the success of the innate immune response during sepsis [93,94]. Recent animal studies have shown that administration of Ig fractions modified by mild oxidation with ferrous ions improves survival after sepsis [95,96]. Interestingly, several investigators have also observed alterations in humoral responses after sepsis, specifically in terms of antigen-specific immunity (e.g.…”

Section: Altered Effector Cd4 T Cell Phenotype And/or Functionmentioning

confidence: 99%

Impact of sepsis on CD4 T cell immunity

Cabrera-Pérez¹,

Condotta

Badovinac

et al. 2014

Journal of Leukocyte Biology

148

124

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Sepsis remains the primary cause of death from infection in hospital patients, despite improvements in antibiotics and intensive-care practices. Patients who survive severe sepsis can display suppressed immune function, often manifested as an increased susceptibility to (and mortality from) nosocomial infections. Not only is there a significant reduction in the number of various immune cell populations during sepsis, but there is also decreased function in the remaining lymphocytes. Within the immune system, CD4 T cells are important players in the proper development of numerous cellular and humoral immune responses. Despite sufficient clinical evidence of CD4 T cell loss in septic patients of all ages, the impact of sepsis on CD4 T cell responses is not well understood. Recent findings suggest that CD4 T cell impairment is a multipronged problem that results from initial sepsis-induced cell loss. However, the subsequent lymphopenia-induced numerical recovery of the CD4 T cell compartment leads to intrinsic alterations in phenotype and effector function, reduced repertoire diversity, changes in the composition of naive antigen-specific CD4 T cell pools, and changes in the representation of different CD4 T cell subpopulations (e.g., increases in Treg frequency). This review focuses on sepsis-induced alterations within the CD4 T cell compartment that influence the ability of the immune system to control secondary heterologous infections. The understanding of how sepsis affects CD4 T cells through their numerical loss and recovery, as well as function, is important in the development of future treatments designed to restore CD4 T cells to their presepsis state.

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Section: Altered Effector Cd4 T Cell Phenotype And/or Functionmentioning

confidence: 99%

Impact of sepsis on CD4 T cell immunity

Cabrera-Pérez¹,

Condotta

Badovinac

et al. 2014

Journal of Leukocyte Biology

148

124

View full text Add to dashboard Cite

show abstract

“…Murine IRA B cells are considered a transitional B-1a-derived subpopulation of B lymphocytes possibly involved in reducing intestinal infections (LPS sepsis models) [5,6], and pneumonia [8]. However, the function of IRA B cells in humans is not known.…”

Section: Resultsmentioning

confidence: 99%

“…They can be identified by the expression of CD19 + IgM + CD5 + CD43 + and the ability to produce granulocyte–macrophage colony-stimulating factor (GM-CSF). These murine cells represent a transitional B-1a-derived population, reside in peritoneal and pleural cavities during the steady state, respond quickly after infection, and expand in the spleen during sepsis (or LPS stimulation) [5,6] and atherosclerosis [7], and in lung fluid in a lung infection model [8]. …”

Section: Introductionmentioning

confidence: 99%

Innate Response Activator (IRA) B Cells Reside in Human Tonsils and Internalize Bacteria In Vitro

et al. 2015

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Innate response activator (IRA) B cells have been described in mice as a subset of B-1a B cells that produce granulocyte/macrophage colony-stimulating factor (GM-CSF) and have been found in the spleen upon activation. In humans, identification, tissue localization and functionality of these lymphocytes are poorly understood. We hypothesized that IRA B cells could reside in human palatine tonsils, which are a first line of defense from infection of the upper respiratory tract. In the present work, we used flow cytometry and confocal microscopy to identify and characterize human IRA (hIRA) B cells in tonsils. We show that CD19+CD20+GM-CSF+ B cells are present in the tonsils of all the subjects studied at a frequency ranging between ~0.2% and ~0.4% of the conventional CD19+CD20+GM-CSF- B cells. These cells reside within the B cell follicles, are mostly IgM+IgD+, express CD5 and show phagocytic activity. Our results support a role for hIRA B cells in the effector immune response to infections in tonsils.

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“…Innate response activator (IRA) CD19 low CD-5 low CD93 + B cells have been implicated recently in the control of experimental sepsis in mice (35). Indeed, our recent studies show that, unlike native IVIg, ferrous ion-modified IVIg induced in the LPS-injected mice had higher levels of IRA B cells, and the beneficial effect of the treatment on survival correlated with this increase (36).…”

Section: Disclosurementioning

confidence: 97%

Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

Djoumerska-Alexieva

Roumenina

Pashov

et al. 2015

Mol Med

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Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as "genomic storm" in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous "danger" signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. online address: http://www.molmed.org

show abstract

The protective effect of modified intravenous immunoglobulin in LPS sepsis model is associated with an increased IRA B cells response

Cited by 13 publications

References 19 publications

Impact of sepsis on CD4 T cell immunity

Impact of sepsis on CD4 T cell immunity

Innate Response Activator (IRA) B Cells Reside in Human Tonsils and Internalize Bacteria In Vitro

Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

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