Intravenous Immunoglobulin: An Update on the Clinical Use and Mechanisms of Action

Negi, Vir-Singh; Elluru, Sri Ramulu; Sibéril, Sophie; Graff‐Dubois, Stéphanie; Mouthon, Luc; Kazatchkine, Michel D.; Lacroix‐Desmazes, Sébastien; Bayry, Jagadeesh; Kaveri, Srini V.

doi:10.1007/s10875-007-9088-9

Cited by 241 publications

(191 citation statements)

References 140 publications

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“…Intravenous immunoglobulin injection to patients at doses of 0.4-2 g/kg generally gives rise to an increase in IgG blood concentration of about 5-10 mg/ml (Morell 1997;Negi et al 2007). Based on our previous observations (de Grandmont et al 2003;Dussault et al 2008), SLE and HC B cells were treated with 10 mg/ml therapeutic immunoglobulin preparation (IVIg) using BSA as the protein supplement control (Fig.…”

Section: Sle B-cell Proliferation and Differentiation Are Both Modulamentioning

confidence: 99%

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

Néron

Boire

Dussault

et al. 2009

Arch. Immunol. Ther. Exp.

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Introduction: Aberrant signaling within and between B and T cells, considered to be central in systemic lupus erythematosus (SLE), could depend on enhanced CD40-CD154 activation. As a result, autoreactive B cells, normally anergic, differentiate and secrete antibodies attacking several normal tissues. Thus restorating B cell homeostasis might help control this disease. In this study, two facets of SLE B cells were investigated, namely their in vitro response to CD40-CD154 and the effect of treatment with human immunoglobulins for intravenous use (IVIg). Materials and Methods: Blood samples from SLE patients and healthy volunteers were obtained and used to isolate B cells, which were activated through CD40 in the presence or absence of IVIg. The phenotype, proliferation, and differentiation of the SLE B cells were determined and compared with those of control B cells using flow cytometry and standard ELISA. Results: In this model, CD40-activated SLE B cells, as control B cells, proliferated and differentiated and were characterized by the emergence of CD19 lo CD38 ++ CD138 + CD27 ++ cells. IVIg treatment of the CD40-activated SLE B cells resulted in higher differentiation, characterized by increased secretion rates of IgG and IgM, as reported previously for control B cells. Conclusions: Taken as a whole, such accelerated differentiation of CD40-activated B cells suggests that IVIg may participate in re-equilibration of the antibody repertoire by replacing pathological antibodies by de novo harmless antibodies.

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Section: Sle B-cell Proliferation and Differentiation Are Both Modulamentioning

confidence: 99%

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

Néron

Boire

Dussault

et al. 2009

Arch. Immunol. Ther. Exp.

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“…These effects enhance the risk of morbidity and mortality, mainly due to infection and relapse in the context of HSCT performed for malignancy. IVIG have been shown to be an effective immunomodulator in many autoimmune diseases 11 and to prevent infections in primary immunodeficiencies. Thus, it was tempting to hypothesize that IVIG might be very attractive in the context of allogeneic HSCT by inhibiting GvHD and preventing infectious diseases.…”

Section: Introductionmentioning

confidence: 99%

Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model

Gregoire-Gauthier

Durrieu

Duval

et al. 2011

Bone Marrow Transplant

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The efficacy of IVIG in preventing GvHD has not been definitely demonstrated clinically. Using a xenogeneic model of GvHD in NOD/SCID/ccÀ (NSG) mice, we showed that weekly administration of IVIG significantly reduced the incidence and associated mortality of GvHD to a degree similar to CsA. Unlike CsA and OKT3, IVIG were not associated with inhibition of human T-cell proliferation in mice. Instead, IVIG significantly inhibited the secretion of human IL-17, IL-2, IFN-c and IL-15 suggesting that IVIG prevented GvHD by immunomodulation. Furthermore, the pattern of modification of the human cytokine storm differed from that observed with CsA and OKT3. Finally, in a humanized mouse model of immune reconstitution, in which NSG mice were engrafted with human CD34 þ stem cells, IVIG transiently inhibited B-cell reconstitution, whereas peripheral T-cell reconstitution and thymopoiesis were unaffected. Together these in vivo data raise debate related to the appropriateness of IVIG in GvHD prophylaxis. In addition, this model provides an opportunity to further elucidate the precise mechanism(s) by which IVIG inhibit GvHD.

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“…21 Augmentation of the cytokine network (decreased proinflammatory and increased anti-inflammatory cytokines), inhibition of cellular activation, differentiation and effector function (antigen presenting cells, B cells and T cells), reduction in complement activation and increased apoptosis of PMNs have all been shown after IVIg administration. 13,64 These effects would provide further biological plausibility for the benefit of IVIg in suppression of overactivated inflammatory cascades in an otherwise competent immune system. However, the immunoregulatory response to IVIg requires specific intact and responsive cellular receptors such as FcgRII, a known negative regulator of inflammation and also downregulated in the leukocytes of very premature neonates.…”

Section: Does Ivig Improve Pmn Function and Sepsis-associated Neutropmentioning

confidence: 99%

“…13 However, immunocompetence requires the presence and concerted effort of multiple immune elements, including immunoglobulin, complement and functional cytotoxic phagocytes. Available evidence indicates that much of this complex system does not function in very premature neonates in the same manner as in more mature neonates, children or adults.…”

Section: Introductionmentioning

confidence: 99%

Does IVIg administration yield improved immune function in very premature neonates?

2010

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Intravenous immunoglobulin (IVIg) has been evaluated as an adjunctive therapy for neonatal sepsis with modest clinical success despite strong biological plausibility. Multiple factors contribute to this outcome, but perhaps none greater than the limited immune system function in newborns, especially in the very premature neonates. For very premature neonates (<30 weeks gestational age), understanding the effects of IVIg on specific immature immune system functions is particularly relevant given their preponderance to develop sepsis and therefore potentially benefit from IVIg-mediated immunoenhancement. Here, we review the available evidence for enhanced immune function after IVIg administration in very premature neonates and highlight areas for future research.

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Intravenous Immunoglobulin: An Update on the Clinical Use and Mechanisms of Action

Cited by 241 publications

References 140 publications

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model

Does IVIg administration yield improved immune function in very premature neonates?

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