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Results for “Immunoglobulins, Intravenous”

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PubMed1999

Supply, use, and abuse of intravenous immunoglobulin.

Intravenous immunoglobulin is used as a replacement therapy in primary immunodeficiency diseases as well as an immunomodulatory agent in a variety of autoimmune and inflammatory disorders. The mechanisms of intravenous immunoglobulin action are complex and, for some disorders, not well understood. This paper reviews the recent literature and discusses approved, new, and controversial indications for intravenous immunoglobulin therapy, with special emphasis on its mechanism of action.

Autoimmune Diseases↗

PubMed2005

The patient: Emerging clinical applications of intravenous immunoglobulin.

Intravenous immunoglobulin (IGIV) originally was used as prophylactic treatment of infections in patients with primary immunodeficiency disease. Today, administration of IGIV, due in large part to its immunomodulatory activity, has expanded to include a number of other disorders. Available data suggest that the accepted indications for IGIV will continue to expand. As the number of clinical applications for this therapy grows, so will market opportunities; current preparations will be modified and improved and new products introduced. Intravenous immunoglobulin therapy has improved the lives of many patients with immune-related disorders. Future applications will ideally advance this paradigm further.

Autoimmune Diseases↗

PubMed1997

Hemolytic anemia associated with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIg) is a useful tool in the treatment of a variety of neuromuscular disorders. Though IVIg therapy is generally safe, hemolytic anemia is a potentially serious complication that is often overlooked, and is currently not listed in product inserts. We analyzed 45 patients who received IVIg therapy, including 38 consecutive patients who received IVIg over a 13-month period. On 42 patients, direct antiglobulin testing was performed, searching for antibodies to the patients' own blood type. Of these 42 patients, 12 developed passive sensitization with antibodies to their own blood group antigens after receiving IVIg. Of these 12 patients, 11 patients developed hemolysis severe enough to lower the hemoglobin level by at least 1 g/dL. Of these patients, 3 required blood transfusion, and 1 had IVIg therapy truncated because of the hemolysis. Antibodies to blood group antigens are found in all commercial preparations of IVIg. Though most patients do not have clinically significant hemolysis, clinicians should be aware of this potentially serious complication. Careful monitoring of hemoglobin levels during IVIg therapy is recommended.

Anemia, Hemolytic↗

PubMed2005

Immunomodulation of autoimmune and inflammatory diseases with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and secondary antibody deficiencies for over two decades. Since the early 1980s, the therapeutic efficacy of IVIg has been established in idiopathic thrombocytopenic purpura, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, dermatomyositis and Kawasaki syndrome, and the prevention of graft versus host disease in recipients of allogeneic bone marrow transplants. Its use has also been reported in a large number of other autoimmune and systemic inflammatory conditions. In this review, we discuss the mechanisms by which IVIg exerts immunomodulatory effects in immune pathologies.

Antigen-Presenting Cells↗

PubMed2005

Therapeutic intravenous immunoglobulins.

Intravenous immunoglobulins (IVIg) are concentrated formulations of human IgG prepared by industrial fractionation of large pools of individual plasma donations. IVIg were developed 20 years ago for the prophylaxis support of immunodeficient patients. However, IVIg have been increasingly used since 10 years, in the treatment of many autoimmune and inflammatory diseases raising the possibility of product shortages and ever increasing costs in the near future. Surprisingly, the immunomodulatory mechanisms of action of IVIg are unclear because of the diversity and often contradictory Fc, F(ab')(2), and non-IgG-related mechanisms that have been proposed from clinical observations and from results obtained in various in vitro and in vivo experimental models. These concepts are reviewed here and we discuss in more details three areas of active research, namely the mechanisms of IVIg action in Idiopathic Thrombocytopenic Purpura (ITP), the effects of IVIg on activated B lymphocytes and the possible involvement of autoantibodies of IgG isotype (auto-IgG) in the immunomodulatory effects of IVIg. The elucidation of the mechanisms of action of IVIg is crucial for a more rationalized clinical use of IVIg and for developing substitutes for some of the immunomodulatory indications in order to ensure long-term availability of plasma-derived IVIg for immunodeficient patients.

Autoantibodies↗

PubMed2004

[Immunomodulatory effects of intravenous immunoglobulins].

Intravenous immunoglobulins (IVIg) are therapeutic preparations of normal human IgG obtained from pools of more than 1000 healthy blood donors. They are currently used in the treatment of a wide range of auto-immune diseases, whether associated with auto-antibodies or auto-reactive T lymphocytes, as well as in the treatment of systemic inflammatory diseases. Several mechanisms of action have been identified during the last 20 years, including: (i) modulation of Fc receptors expression on leukocytes and endothelial cells; (ii) interaction with complement proteins; (iii) modulation of cytokines and chemokines synthesis and release; (iv) modulation of cell proliferation and apoptosis; (v) remyelinisation; (vi) neutralisation of circulating autoantibodies; (vii) selection of repertoires of B and T lymphocytes; (viii) interaction with other cell-surface molecules on lymphocytes and monocytes; (ix) corticosteroid sparing. These mechanisms of action are multiple and often intricate. However, they are still little known and further investigations are warranted.

Apoptosis↗

PubMed2006

[Indications for intravenous immunoglobulins].

Intravenous immunoglobulins (IgIV) are therapeutic preparations of polyclonal human IgG, obtained from a pool of plasma from more than 1000 healthy donors. This article discusses only some of the recognized indications (Group I) and some of those currently under evaluation (Group II) for the treatment of autoimmune and systemic inflammatory diseases. Perspectives for IgIV use are approached through three diseases, each providing a different model of immune system modulation: ocular cicatricial pemphigoid, where an autoimmune reaction is modulated; alloimmunization of chronic hemodialysis patients, where alloreactivity can be modulated; and streptococcal toxic shock, where anti-infectious immunity may be modulated.

Acquired Immunodeficiency Syndrome↗

PubMed2003

[Therapeutic indications of intravenous immunoglobulins].

Intravenous Immunoglobulin (IVIg) provide a wide spectrum of antibody specificities in patients with antibody deficiencies and restore immune homeostasis in patients with auto-immune diseases. Controlled trials have now been performed in a large number of diseases: in primary and secondary antibody deficiencies, auto-immune neurological diseases and various other auto-immune or systemic inflammatory conditions. Mechanisms of action of IVIg are multiple and often associated for a given disease. These mechanisms are however incompletely understood and therapeutic effect of IVIg remains to be investigated in a wide range of diseases.

Antibody Specificity↗

PubMed2003

Prospective audit of adverse reactions occurring in 459 primary antibody-deficient patients receiving intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) is used as the standard replacement therapy for patients with primary antibody deficiencies. A previous study of adverse reactions in patients self-infusing at home over 1 year showed an overall reaction rate of 0.7%. A larger prospective study is reported here, involving a greater number of immunology centres and including children and adults who received infusions from medical or nursing staff as well as those self-infusing. Four hundred and fifty-nine patients were entered into this study and 13 508 infusions were given. The study showed that no severe reactions occurred and the reaction rate was low at 0.8%. This figure could have been lower, 0.5%, if predisposing factors responsible for some reactions had been considered before infusion. In conclusion, the study shows the importance of ongoing training for patients and staff to recognize the predisposing factors to prevent avoidable reactions. Because none of these reactions were graded as severe, the present guidance to prescribe self-injectable adrenaline for patients infusing outside hospital should be reviewed.

Adolescent↗

PubMed1997

Side effects of high-dose intravenous immunoglobulins.

Intravenous immunoglobulins (IVIgs) are used increasingly as therapy for neuroimmunologic and other autoimmune diseases. With broader use, the number of reported side effects also is growing. Here we review the literature on adverse reactions reported after administration of i.v.Igs. Despite a few recent reports about a high frequency of complications of IVIgs, by and large they can be considered as safe. Mild and self-limited side effects may occur, but severe complications are rare and often associated with other risk factors for these complications. A careful screening for preexisting illnesses and monitoring of some laboratory parameters can minimize the risks of IVIg therapy.

Dose-Response Relationship, Drug↗

PubMed2006

Expression of chemokine receptors on peripheral blood mononuclear cells of patients with immune-mediated neuropathies treated with intravenous immunoglobulins.

Intravenous immunoglobulin (IVIg) is an efficacious treatment for immune-mediated neuropathies like Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating neuropathy (CIDP), and multifocal motor neuropathy (MMN). In the pathogenesis of immune-mediated neuropathies chemokines and their receptors play a crucial role. Using flow cytometry we examined whether IVIg modulates chemokine expression repertoires of T cells and monocytes. The expression of inflammatory chemokine receptors CCR1, CCR2, CCR4, CCR5, CCR6 and CXCR3 was investigated on circulating T-cell subsets, and CCR1, CCR2 and CCR5 on circulating monocytes before and after IVIg treatment in patients with immune-mediated neuropathies (MMN, n = 7; GBS, n = 1; CIDP, n = 2). Furthermore, the homing potential of T cells was analyzed by the expression of CCR7, a chemokine receptor known to be utilized by mature T cells to recirculate into secondary lymphoid organs. In contrast to studies in chronic heart failure, no differences in expression patterns before and after IVIg treatment of any of the investigated chemokine receptors were found. Furthermore, the proportion of CD45RO-positive CD4+ or CD8+ T-cell subsets was not changed by IVIg treatment. Thus, we concluded that modulation of the expression of chemokine receptors on circulating leukocytes by IVIg is not a mode of action in immune-mediated neuropathies.

Adult↗

PubMed2005

Comparative analysis of antigen specificities in the monomeric and dimeric fractions of intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) preparations are derived from the pooled plasma of thousands of healthy donors and contain a complex mix of antibodies. Depending on the formulation, IVIG preparations contain variable amounts of monomeric and dimeric IgG. The biological and therapeutic significance of these IVIG fractions is still ill defined. Kinetic analysis of monomeric and dimeric IgG isolated by size-exclusion chromatography revealed a stable monomeric versus an unstable dimeric IgG fraction tending to dissociation. Biochemical analysis by 2D gel electrophoresis and isotype analysis showed no significant differences between the fractions. In contrast, comparative analysis by immunodot, ELISA, FACS, and immunohistology of monomeric and dimeric IgG fractions showed a preferential reactivity of the dimeric IgG on a variety of both self-antigens and exoantigens.

Animals↗

PubMed2005

Facing the enigma of immunomodulatory effects of intravenous immunoglobulin.

Intravenous immunoglobulin (IVIg) is a safe remedy for a number of conditions; it is produced from human plasma of thousands of healthy donors. The therapeutic effect of IVIg lies within its content. IVIg contains natural antibodies, which are more polyreactive than immune antibodies, including immunoglobulin G antibodies against endogenous and exogenous antibodies, immunomodulating peptides, and varies cytokines. Beneficial effects of IVIg have been established in immunodeficiencies, as well as in some autoimmune diseases. Also, numerous therapeutic effects of IVIg have been reported over the years in varies autoimmune diseases, recurrent pregnancy loss, and cancer. Many proposed immunoregulatory mechanisms of action of IVIg have been suggested. Some of them have been proven, others are still an enigma, at least in part. Some of these mechanisms entail (a) Fc-receptor blockade; (b) neutralization of pathogenic autoantibodies via idiotypic and anti-idiotypic antibodies; (c) effects on the Fas apoptotic pathway via agonistic and antagonistic anti-Fas autoantibodies; (d) regulation of complement components; (e) modulation of cytokine secretion; (f) hindrance of natural-killer cell activity; (g) inhibition of matrix metalloproteinase-9; (h) suppression of NFkB activation and IkB degradation; (i) G1 cell cycle arrest; (j) prevention of tumor growth; (k) decrease in leukocyte recruitment; (l) attenuation of T-cell stimulation; (m) effects on antibody kinetics; and (n) effects on dendritic cells. The variant mechanisms of IVIg are believed to cooperate in a synergistic way, which all together point to IVIg as a therapeutic preparation with anti-inflammatory, antiself-reactivity, antimetastatic, and embryo-protective effects. This article reviews several main mechanisms of IVIg in order to shed some light on the set of therapeutic effects of IVIg, which are not yet fully understood.

Animals↗

PubMedDate not supplied

Immunomodulation, part III: intravenous immunoglobulin.

Intravenous immunoglobulin therapy does not appear to be efficacious in the prevention of neonatal sepsis. The value of a 3-4 percent reduction in sepsis or any serious infection without a reduction in mortality must be weighed against the cost of the therapy. The efficacy of IVIG therapy in the treatment of neonatal sepsis remains uncertain. The results of the ongoing International Neonatal Immunotherapy Study should provide definitive answers regarding the effectiveness of this therapy. Long-term follow-up and cost (length of stay) are important components of this study. Ohlsson and Lacy recommend studies evaluating the effectiveness of IVIG preparations with high concentrations of antibodies to common unit- or geography-specific pathogens. The cost-effectiveness of the production and use of such products should be included in study designs. Part IV of this series will explore the use of the amino acid glutamine as an immunomodulating agent in neonates.

Drug Administration Schedule↗

PubMed1999

Successful treatment of severe muscle necrosis with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) is an effective treatment for a range of conditions believed to have an autoimmune basis, including inflammatory muscle disease. We describe a patient with muscle disease characterized by severe necrosis without clinical or biopsy evidence of inflammation or vasculitis, who responded to treatment with IVIG.

Biopsy↗

PubMed2000

[Immunomodulatory effects of intravenous immunoglobulins].

Intravenous immunoglobulin (IVIg) has been used for many years in the treatment of primary and secondary antibody deficiencies. IVIg was first demonstrated to be effective in auto-immune desorders twenty years ago in the treatment of idiopathic thrombocytopenic purpura. The beneficial effect of IVIg has since been established in the Guillain-Barré syndrome, chronic inflammatory demenilating polyneuropathy, myasthenia gravis, dermatomyositis, Kawasaki syndrome and graft versus host disease. The beneficial effect of IVIg has been suggested in a large number of other auto-immune and systemic inflammatory conditions. The mode of action of IVIg is complex, involving Fc receptor blockade, interference with complement activation and the cytokine network, provision of anti-idiotypic antibodies and modulation of T and B cell activation and differentiation. Such a broad range of activities reflects the function of normal circulating immunoglobulins in maintaining tolerance to self in healthy individuals.

Adjuvants, Immunologic↗

PubMedDate not supplied

Home infusion of intravenous immunoglobulin.

Intravenous immunoglobulin (IGIV) is being used extensively in the home-care setting to treat patients with a wide variety of disorders. This therapy can be managed more effectively when the patient and/or caregiver have been educated regarding the therapy. In this article, a therapy education plan, policies, and procedures that address the key components of providing IGIV treatments in the home-care setting will be presented. Instructional information is presented in "patient-friendly terms" that can be readily applied to the nursing care plan. This plan will be applicable for patients who will become independent with the administration of their IGIV as well as for those who will have their IGIV administered by the home-care nurse.

Home Infusion Therapy↗

PubMed1989

Prevention of recurrent spontaneous abortion by intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) treatment was attempted as a novel therapeutic approach for unexplained recurrent spontaneous abortions (RSA) occurring in the first trimester of pregnancy. Twenty women with a history of RSA were treated with IVIG during pregnancy. Therapy was commenced at week 5 of gestation with 1 dose of 0.5-0.6 g IVIG/kg body weight. Infusions were repeated every 3 weeks (0.3-0.4 g/kg) and terminated by week 22 to 24. Of 20 women, 11 delivered healthy infants at term. 5 women are still pregnant, 3 in the third trimester. Only 3 patients suffered abortions and 1 presented with ectopic pregnancy. The overall success rate was 82-86%. Thus, the therapeutic effect of IVIG is comparable to that of the conventional transfusion/vaccination regimen with allogeneic leukocytes, but avoids the risk of transmission of infections and/or HLA immunization, has no major adverse effects and is applicable to 'nonresponders'.

Abortion, Habitual↗