RESUMO
Although immunoglobulin (Ig) has been available since the 1950s for replacement therapy in primary immune deficiency, many other effective uses of this class of biologics have been investigated and evolved over recent decades. Ig administration has become common practice in the treatment of the immunocompromised patient and has recently expanded into the treatment of those patients with an inflammatory disease and autoimmune neuropathies per established clinical guidelines. As research into the genetic basis of disease advances, clinicians should better assess complex data surrounding safe and effective uses of Ig to treat patients who present with B-cell and T-cell deficiencies, along with those harboring gene deletions or genetic anomalies who may potentially benefit from Ig therapy. Evidence-based clinical indications for the use of Ig include idiopathic thrombocytopenic purpura, B-cell chronic lymphocytic leukemia, Kawasaki disease, chronic idiopathic demyelinating polyneuropathy, multifocal motor neuropathy, bone marrow transplantation, and pediatric HIV infection, among others, and have evolved over time. Ig is also often tried in refractory cases that might benefit from its anti-inflammatory effects or empirically in off-label situations. Due to its anti-inflammatory effects, high-dose Ig has been used for numerous off-label indications with varying levels of effectiveness and evidence to support its use. A review of all autoimmune conditions for which Ig has been used is beyond the scope of this article and newer treatments are available for many of these disorders. Here the focus will be on selected conditions in which Ig has clear benefit. Because there is a limited supply of Ig and a need for further research into optimal use, it is important for healthcare professionals to better understand current and developing indications and data/levels of evidence to support Ig therapy as its role continues to evolve.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/história , Imunoglobulinas Intravenosas/história , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/história , História do Século XX , História do Século XXIRESUMO
The two main indications for the use of intravenous gammaglobulin--antibody replacement therapy and immunomodulation--are pertinent only for a few scenarios in HIV-1 infection. The role of gammaglobulin in the treatment of HIV-1 infection has changed significantly with the introduction of highly active antiretroviral therapy. Antiretroviral drugs have not only controlled the progression of disease but also had far-reaching effects on HIV-1-induced immunologic aberrations. Complete or partial immunologic reconstitution and prevention of immunologic damage have been the hallmarks of success for highly active antiretroviral therapy. This article addresses the use of gammaglobulin before and after the era of effective antiretroviral therapies.
Assuntos
Infecções por HIV/terapia , HIV-1/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Adulto , Linfócitos B/imunologia , Linfócitos B/metabolismo , Criança , Feminino , Infecções por HIV/imunologia , História do Século XX , História do Século XXI , Humanos , Imunidade Materno-Adquirida , Imunoglobulinas Intravenosas/história , Síndromes de Imunodeficiência/terapia , Recém-Nascido , GravidezRESUMO
The original rationale for the therapeutic application of immunoglobulins was prevention and treatment of infectious diseases. With the description of agammaglobulinemia, substitution therapy became the primary indication for the use of immunoglobulins. Limitations and side effects of the intramuscular administration of immunoglobulins led to the development of preparations for intravenous use (IVIg). In the early 1980s an immunomodulatory effect of IVIg was described. Since then, the efficacy of IVIg has been established in controlled trials for diseases like idiopathic thrombocytopenic purpura, Kawasaki disease, Guillain-Barré syndrome, dermatomyositis, and many others. There is a large body of evidence that IVIg can modulate an immune reaction at the level of T cells, B cells, and macrophages, interferes with antibody production and degradation, modulates the complement cascade, and has effects on the cytokine network. However, the precise mechanism of action is not yet clear.
Assuntos
Imunoglobulinas Intravenosas/farmacologia , Imunoglobulinas Intravenosas/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/imunologia , História do Século XX , Humanos , Imunoglobulinas Intravenosas/história , Imunoglobulinas Intravenosas/imunologia , Doenças do Sistema Nervoso/imunologiaRESUMO
Intravenous immunoglobulin (IVIgG) has many potential applications in haematology both as antibody replacement therapy and as an immune-modulater in autoimmune disorders. Antibody replacement appears to be of value in the prophylaxis of infection in low-grade B-cell malignancies, in bone marrow transplant recipients and in children with AIDS, although optimal treatment strategies have not been assessed and determining which patients are likely to derive greatest benefit has been problematic. IVIgG appears to be effective in the prevention or amelioration of CMV-related pathology if given frequently and has also dramatically improved the survival of patients with established interstitial pneumonia when used in combination with ganciclovir. Intriguingly, IVIgG appears to moderate the severity of GVHD in adult transplant recipients. IVIgG has short term efficacy in most patients with ITP but, as long term remissions are uncommon, it has become necessary to be more selective in the use of IVIgG in this disorder. The response to IVIgG in other immune-mediated cytopenias is similar with generally transient improvement but also with occasional spectacular cures. The treatment of the acquired haemophilias with IVIgG has yielded in vivo and vitro evidence to support the idiotype-antiidiotype theory of IVIgG immune-modulation and has also demonstrated significant differences in the sensitivity of coagulation factor autoantibodies and alloantibodies to IVIgG therapy. IVIgG has several roles in pregnancy related disorders, including the management of both mother and fetus in ITP during pregnancy, the antenatal and postnatal management of platelet alloimmunisation and also in the management of severe rhesus isoimmunisation. IVIgG is safe and well tolerated. The expense of this therapy should be balanced against the likely gains and the overall costs of alternative approaches.
Assuntos
Doenças Hematológicas/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Fatores de Coagulação Sanguínea/antagonistas & inibidores , Transplante de Medula Óssea/imunologia , Infecções por HIV/terapia , História do Século XIX , História do Século XX , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Imunoglobulinas Intravenosas/história , Neoplasias/imunologia , Neoplasias/terapia , Púrpura Trombocitopênica Idiopática/terapiaRESUMO
The search for preparations of human gammaglobulin that could be administered safely intravenously was driven by the need to better manage immune deficiency states. However, when suitable formulations were developed, it was soon realised that large infusions of immunoglobulin could be used to manipulate the immune system. The production of autoantibodies was minimised or their effects neutralised; T cell effector and regulatory function could be manipulated and cytokine release modified. More than fifty human disease states, many until now lacking safe and effective therapies, can be improved by the administration of intravenous immunoglobulin. Better understanding of the mechanisms involved will not only improve therapy but will provide a better understanding of the immunopathogenic mechanisms responsible.
Assuntos
Autoimunidade/fisiologia , Imunoglobulinas Intravenosas/história , Imunoglobulinas Intravenosas/fisiologia , Autoanticorpos/imunologia , Citocinas/efeitos dos fármacos , História do Século XX , Humanos , Imunização Passiva , Imunoglobulinas Intravenosas/química , Receptores Fc/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
Since 1946 the development of fractionation and purification methods of human plasma led to biologic immunoglobulin for intravenous use (IVIG). In 1980 a child with refractory immune thrombocytopenia (ITP), bleeding and secondary hypogammaglobulinaemia due to long term immunosuppressive treatment got IVIG. His platelet counts dramatically increased. In 13 consecutive children with ITP, but without hypogammaglobulinaemia, similar rapid platelet increases were observed and confirmed in a controlled, multicentre study. During the past three decades this biologic treatment modality evoked clinical and laboratory research on the mechanisms of action and in disorders with similar immune pathogenesis. It was recognised that IVIG modulates the disturbed immune response in multiple, synergistic ways between the different components of the immune system. Beside other immune hematologic disorders other inflammatory and autoimmune diseases, mainly in the field of neurology and dermatology, IVIG showed beneficial effects. The worldwide consumption of IVIG increased from 300 kg per year in 1980 to 100 tonnes per year in 2010. Due to the heterogeneity of immunopathological mechanisms of autoimmune diseases evidence based indications of IVIG remain rare and off label use high. Registries of large numbers of patients and first endpoints of defining less heterogenous subgroups in immune related disorders are the next steps toward establishment of evidence based IVIG indications.