scholarly journals In vitro and in vivo properties differ among liquid intravenous immunoglobulin preparations

Vox Sanguinis ◽  
2012 ◽  
Vol 104 (2) ◽  
pp. 115-126 ◽  
Author(s):  
F. Dhainaut ◽  
P.‐O. Guillaumat ◽  
H. Dib ◽  
G. Perret ◽  
A. Sauger ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Immunoglobulin Preparations

Immunoglobulin M–Enriched Human Intravenous Immunoglobulin Prevents Complement Activation In Vitro and In Vivo in a Rat Model of Acute Inflammation

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 942-951 ◽  
Author(s):  
Robert Rieben ◽  
Anja Roos ◽  
Yvonne Muizert ◽  
Caroline Tinguely ◽  
Arnout F. Gerritsen ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Complement Activation ◽  
Inhibitory Activity ◽  
Solid Phase ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Glomerular Mesangial Cells ◽  
Immunoglobulin Preparations

An important antiinflammatory mechanism of intravenous immunoglobulin preparations (IVIG) is their ability to block complement activation. The purpose of this study was to compare the complement-inhibitory activity of four IVIG preparations differing in isotype composition. The preparations were: (1) IVIgG (48 g/L IgG, 2 g/L IgA; Intraglobin F); (2) Pentaglobin (38 g/L IgG, 6 g/L IgM, 6 g/L IgA); (3) IVIgM (35 g/L IgM, 12 g/L IgA, 3 g/L IgG); and (4) IVIgA (41 g/L IgA, 9 g/L IgG), all from Biotest Pharma GmbH, Dreieich, Germany. Their complement inhibitory activity was assessed in vitro by measurement of the blocking of C1q-, C4-, and C3 deposition on solid-phase aggregated rabbit IgG by enzyme-linked immunosorbent assay (ELISA). Complement inhibition in this ELISA was best for IVIgM, followed by Pentaglobin and IVIgG; IVIgA did not exhibit an inhibitory effect. Control experiments with excess concentrations of C1q as well as with C1q-depleted serum showed that the inhibitory effects of IVIG were not caused by complement activation and thus, consumption, but that C4 and C3 were scavenged by IgM and to a lesser extent by IgG. These results were confirmed in vivo in the rat anti-Thy 1 nephritis model, in which a single dose of 500 mg/kg of IVIgM prevented C3-, C6-, and C5b-9 deposition in the rat glomeruli, whereas the effect of IVIgG was much less pronounced. Reduction of complement deposition was paralleled by a diminished albuminuria, which was completely absent in the IVIgM-treated rats. IVIgM and to a lesser extent IVIgG also prevented rat C3 deposition on cultured rat glomerular mesangial cells in vitro, but did not influence anti-Thy 1 binding. Neither IVIgM nor Pentaglobin nor IVIgG negatively affected in vitro phagocytosis of Escherichia coli (E coli) by human granulocytes. In conclusion, we have shown that IgM enrichment of IVIG preparations enhances their effect to prevent the inflammatory effects of complement activation.

Immunoglobulin M–Enriched Human Intravenous Immunoglobulin Prevents Complement Activation In Vitro and In Vivo in a Rat Model of Acute Inflammation

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 942-951 ◽  
Author(s):  
Robert Rieben ◽  
Anja Roos ◽  
Yvonne Muizert ◽  
Caroline Tinguely ◽  
Arnout F. Gerritsen ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Complement Activation ◽  
Inhibitory Activity ◽  
Solid Phase ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Glomerular Mesangial Cells ◽  
Immunoglobulin Preparations

Abstract An important antiinflammatory mechanism of intravenous immunoglobulin preparations (IVIG) is their ability to block complement activation. The purpose of this study was to compare the complement-inhibitory activity of four IVIG preparations differing in isotype composition. The preparations were: (1) IVIgG (48 g/L IgG, 2 g/L IgA; Intraglobin F); (2) Pentaglobin (38 g/L IgG, 6 g/L IgM, 6 g/L IgA); (3) IVIgM (35 g/L IgM, 12 g/L IgA, 3 g/L IgG); and (4) IVIgA (41 g/L IgA, 9 g/L IgG), all from Biotest Pharma GmbH, Dreieich, Germany. Their complement inhibitory activity was assessed in vitro by measurement of the blocking of C1q-, C4-, and C3 deposition on solid-phase aggregated rabbit IgG by enzyme-linked immunosorbent assay (ELISA). Complement inhibition in this ELISA was best for IVIgM, followed by Pentaglobin and IVIgG; IVIgA did not exhibit an inhibitory effect. Control experiments with excess concentrations of C1q as well as with C1q-depleted serum showed that the inhibitory effects of IVIG were not caused by complement activation and thus, consumption, but that C4 and C3 were scavenged by IgM and to a lesser extent by IgG. These results were confirmed in vivo in the rat anti-Thy 1 nephritis model, in which a single dose of 500 mg/kg of IVIgM prevented C3-, C6-, and C5b-9 deposition in the rat glomeruli, whereas the effect of IVIgG was much less pronounced. Reduction of complement deposition was paralleled by a diminished albuminuria, which was completely absent in the IVIgM-treated rats. IVIgM and to a lesser extent IVIgG also prevented rat C3 deposition on cultured rat glomerular mesangial cells in vitro, but did not influence anti-Thy 1 binding. Neither IVIgM nor Pentaglobin nor IVIgG negatively affected in vitro phagocytosis of Escherichia coli (E coli) by human granulocytes. In conclusion, we have shown that IgM enrichment of IVIG preparations enhances their effect to prevent the inflammatory effects of complement activation.

scholarly journals Intravenous immunoglobulin preparations induce mild activation of neutrophils in vivo via triggering of macrophages - studies in a rat model

2001 ◽  
Vol 112 (4) ◽  
pp. 1031-1040 ◽  
Author(s):  
Jessica L. Teeling ◽  
Wim K. Bleeker ◽  
Gemma M. M. Rigter ◽  
Nico Van Rooijen ◽  
Taco W. Kuijpers ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Rat Model ◽  
Immunoglobulin Preparations

Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase

Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1856-1861 ◽  
Author(s):  
Wim K. Bleeker ◽  
Jessica L. Teeling ◽  
Arthur J. Verhoeven ◽  
Gemma M. M. Rigter ◽  
Jacques Agterberg ◽  
...  
Keyword(s):  
Side Effects ◽  
Intravenous Immunoglobulin ◽  
Rat Model ◽  
Platelet Activating Factor ◽  
Human Neutrophils ◽  
Ivig Infusion ◽  
Platelet Activating Factor Acetylhydrolase ◽  
Paf Acetylhydrolase ◽  
Immunoglobulin Preparations

Previously, we observed in a rat model that intravenous administration of intramuscular immunoglobulin preparations induced a long-lasting hypotension, which appeared to be associated with the presence of IgG polymers and dimers in the preparations, but unrelated to complement activation. We found evidence that this hypotensive response is mediated by platelet-activating factor (PAF) produced by macrophages. In this study, we compared the vasoactive effects of 16 intravenous immunoglobulin (IVIG) products from 10 different manufacturers, in anesthetized rats. Eight of the IVIG preparations showed no hypotensive effects (less than 15% decrease), whereas the other 8 had relatively strong effects (15%-50% decrease). The hypotensive effects correlated with the IgG dimer content of the preparations. Pretreatment of the rats with recombinant PAF acetylhydrolase completely prevented the hypotensive reaction on IVIG infusion, and administration after the onset of hypotension resulted in normalization of the blood pressure. We also observed PAF production on in vitro incubation of human neutrophils with IVIG, which could be blocked by anti-Fcγ receptor antibodies. This indicates that induction of PAF generation may also occur in a human system. Our findings support the hypothesis that the clinical side effects of IVIG in patients may be caused by macrophage and neutrophil activation through interaction of IgG dimers with Fcγ receptors. Because phagocyte activation may also lead to the release of other inflammatory mediators, recombinant PAF acetylhydrolase (rPAF-AH) provides a useful tool to determine whether PAF plays a role in the clinical side effects of IVIG. If so, rPAF-AH can be used for the treatment of those adverse reactions.

scholarly journals Intravenous Immunoglobulin and Immunomodulation of B-Cell – in vitro and in vivo Effects

2015 ◽  
Vol 6 ◽  
Author(s):  
Milica Mitrevski ◽  
Ramona Marrapodi ◽  
Alessandro Camponeschi ◽  
Filomena Monica Cavaliere ◽  
Cristina Lazzeri ◽  
...  
Keyword(s):  
B Cell ◽  
Intravenous Immunoglobulin ◽  
In Vivo Effects

PRIMARY IMMUNODEFICIENCIES

PEDIATRICS ◽  
1971 ◽  
Vol 47 (5) ◽  
pp. 927-946
Author(s):  
H. Fudenberg ◽  
R. A. Good ◽  
H. C. Goodman ◽  
W. Hitzig ◽  
H. G. Kunkel ◽  
...  
Keyword(s):  
Primary Immunodeficiency ◽  
Relative Effectiveness ◽  
Diagnostic Procedures ◽  
Malignant Tumour ◽  
In Vitro Tests ◽  
Cell Mediated Immunity ◽  
Immunoglobulin Preparations ◽  
Pathological Material

1. Two registries are to be established in association with WHO, with the object of gathering and recording information on cases of immunodeficiency from all over the world. One registry will comprise cases of primary immunodeficiency that have received transplants of any immunologically competent organ, cell, or cell product, e.g., bone marrow, thymus, or transfer factor. It will be organized by W. Hitzig and M. Seligmann. The other will comprise cases of malignant tumour found in patients with primary immunodeficiency; it will be organized by R. A. Good, who will also arrange for pathological material to be submitted for study by selected pathologists. The organizers will collate and periodically report on the material in both registries. 2. Standardization of diagnostic procedures and additional studies related to diagnostic tests are required. a. There is a need for standard preparations of antigens for assessing antibody formation as described. A sufficiently large batch of such antigens should be prepared, and aliquots should be sent, on request, for use by clinicians investigating immunodeficiency. b. Methods for measuring serum antibodies need to be standardized, and in vitro tests for the measurement of cell-mediated immunity, such as tests for cytotoxicity and macrophage migration inhibition factors, need to be further developed. 3. Therapeutic procedures should be standardized and assessed. a. Aggregates in immunoglobulin preparations for intramuscular or intravenous injection should be looked for with tests such as those recommended. b. National agencies responsible for immunoglobulin production should develop stable aggregate-free intact IgG, without fragments and with relatively normal in vivo survival, for the treatment of patients with immunodeficiency. c. It would be of value to determine the relative effectiveness of therapy with immunoglobulin and with plasma. Clinical trials might be designed for this purpose. d. Immunoglobulin preparations having high contents of specific antibodies would, if available, be valuable for treatment of patients with specific infections. e. Further research is required to develop new methods of destroying the biological activity of lymphocytes in whole blood. f. Pools of immunoglobulin, prepared as Cohn FII from donors with absence of One genetic allotype, may be valuable for the treatment of patients with immunodeficiency who have anti-allotype antibodies.

scholarly journals A microtubule-associated protein antigen unique to mitotic spindle microtubules in PtK1 cells.

1983 ◽  
Vol 96 (2) ◽  
pp. 424-434 ◽  
Author(s):  
J G Izant ◽  
J A Weatherbee ◽  
J R McIntosh
Keyword(s):  
Mitotic Spindle ◽  
Microtubule Network ◽  
Mitotic Apparatus ◽  
Microtubule Associated Proteins ◽  
Immunoglobulin Preparations ◽  
Rapid Dissolution ◽  
Associated Proteins ◽  
Cultured Human Cells

Microtubule-associated proteins (MAPs) that copurify with tubulin through multiple cycles of in vitro assembly have been implicated as regulatory factors and effectors in the in vivo activity of microtubules. As an approach to the analysis of the functions of these molecules, a collection of lymphocyte hybridoma monoclonal antibodies has been generated using MAPs from HeLa cell microtubule protein as antigen. Two of the hybridoma clones secrete IgGs that bind to distinct sites on what appears to be a 200,000-dalton polypeptide. Both immunoglobulin preparations stain interphase and mitotic apparatus microtubules in cultured human cells. One of the clones (N-3B4.3.10) secretes antibody that reacts only with cells of human origin, while antibody from the other hybridoma (N-2B5.11.2) cross-reacts with BSC and PtK1 cells, but not with 3T3 cells. In PtK1 cells the N-2B5 antigen is associated with the microtubules of the mitotic apparatus, but there is no staining of the interphase microtubule array; rather, the antibody stains an ill-defined juxtanuclear structure. Further, neither antibody stains vinblastine crystals in either human or marsupial cells at any stage of the cell cycle. N-2B5 antibody microinjected into living PtK1 cells binds to the mitotic spindle, but does not cause a rapid dissolution of either mitotic or interphase microtubule structures. When injected before the onset of anaphase, however, the N-2B5 antibody inhibits proper chromosome partition in mitotic PtK1 cells. N-2B5 antibody injected into interphase cells causes a redistribution of MAP antigen onto the microtubule network.

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