Clinical applications of intravenous immunoglobulins (IVIg)--beyond immunodeficiencies and neurology

Abstract

The clinical use of intravenous immunoglobulin (IVIg) has expanded beyond its traditional place in the treatment of patients with primary immunodeficiencies. Due to its multiple anti-inflammatory and immunomodulatory properties, IVIg is used successfully in a wide range of autoimmune and inflammatory conditions. Recognized autoimmune indications include idiopathic thrombocytopenic purpura (ITP), Kawasaki disease, Guillain-Barré syndrome and other autoimmune neuropathies, myasthenia gravis, dermatomyositis and several rare diseases. Several other indications are currently under investigation and require additional studies to establish firmly the benefit of IVIg treatment. Increasing attention is being turned to the use of IVIg in combination with other agents, such as immunosuppressive agents or monoclonal antibodies. For example, recent studies suggest that combination therapy with IVIg and rituximab (an anti-CD20 monoclonal antibody) may be effective for treatment of autoimmune mucocutaneous blistering diseases (AMBDs), with sustained clinical remission. The combination of IVIg and rituximab has also been used in the setting of organ transplantation. Firstly, IVIg +/- rituximab has been administered to highly human leucocyte antigen (HLA)-sensitized patients to reduce anti-HLA antibody levels, thereby allowing transplantation in these patients. Secondly, IVIg in combination with rituximab is effective in the treatment of antibody-mediated rejection following transplantation. Treatment with polyclonal IVIg is a promising adjunctive therapy for severe sepsis and septic shock, but its use remains controversial and further study is needed before it can be recommended routinely. This review covers new developments in these fields and highlights the broad range of potential therapeutic areas in which IVIg may have a clinical impact.

Fig. 1

Panel-reactive antibody titres pre- and post-intravenous immunoglobulin (IVIg) plus rituximab treatment. Individual data from the 20 study patients before the first infusion of IVIg and after the second infusion are shown. The pretreatment and post-treatment means are also shown, as determined with the T cell complement-dependent cytotoxicity panel-reactive antibody assay. The means were significantly different (P < 0·001). Error bars denote standard deviations. Reproduced with permission from Vo et al. 2008 [5].

Fig. 2

Patient and graft survival 2 years post-transplant for 113 highly-sensitized dialysis patients transplanted after desensitization with intravenous immunoglobulin (IVIg) plus rituximab. Patient and graft survival rates were 98% and 93%, respectively.

Fig. 3

Forrest plot showing the overall effect of intravenous immunoglobulin (IVIg) on mortality in adults with sepsis. CI: confidence interval. Reproduced with permission from Laupland et al. 2007 [70].