Intravenous immunoglobulin therapy in rheumatic diseases

Abstract

Prepared from the collective plasma of several thousand people, therapeutic intravenous immunoglobulin (IVIg) consists mostly of human polyspecific IgG. In addition to its use in primary and secondary immune deficiencies, IVIg is used in the treatment of several rheumatic conditions, including Kawasaki disease, dermatomyositis and antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. In these diseases, IVIg therapy generally involves the use of 2 g/kg administered over either 2 or 5 consecutive days. However, dosage regimens have not been thoroughly explored, and indications for IVIg in most rheumatic diseases, such as systemic lupus erythematosus, polymyositis and catastrophic antiphospholipid syndrome, derive from its off-label usage. Randomized clinical trials are warranted to support the evidence-based use of IVIg, and to identify the ideal administration protocols to maximize the benefits of what is a limited resource. Further research to improve the therapeutic application of IVIg relies essentially on the conception of next-generation immunoglobulin preparations and optimization of combined therapies with immunomodulatory drugs and biologic agents.

Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity

“…Although efficacious in these diseases, the precise mechanism of action of IVIg is not well-understood. Various studies have documented a series of nonmutually exclusive mechanisms modulating components of the innate and adaptive immune system (4,6). For example, IVIg has been shown to mediate anti-inflammatory responses through its action on dendritic cells, natural killer cells, regulatory T cells, B cells, and the monocyte/macrophage system, and through its suppression or neutralization of soluble factors, such as inflammatory cytokines, chemokines, and pathogenic autoantibodies (5)(6)(7).…”

Intravenous immunoglobulin-mediated expansion of regulatory T cells in autoimmune patients is associated with increased prostaglandin E2 levels in the circulation

“…Currently, high-dose IVIg therapy (1-2 g/kg body weight) is used in the treatment of diverse autoimmune and inflammatory conditions, such as Guillain-Barré syndrome (GBS), Kawasaki disease, idiopathic thrombocytopenic purpura and inflammatory myositis. 1 The beneficial effects of IVIg are mediated by numerous mutually non-exclusive cellular and molecular mechanisms. These mechanisms indirectly suggest the functions of circulating IgG in the maintenance of immune homeostasis.…”

The protective role of immunoglobulins in fungal infections and inflammation

“…However, a recent study suggested that Efungumab potentiation of amphotericin B could be non-specific [108]. Although a status of an orphan drug has been given in USA for this antibody, Initially used for the replacement therapy of primary and secondary immunodeficiencies, high-dose (1-2 g/kg body weight) IVIg is currently used in the therapy of diverse autoimmune and inflammatory diseases such as Kawasaki disease, Guillain-Barré Syndrome, inflammatory myopathies, immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, vasculitis, graft versus host disease, and others as an immunomodulatory agent with no reports of serious side effects [110][111][112][113][114][115]. In addition to invasive disease, fungi species are also associated with several inflammatory conditions such as both IgE and eosinophiliadriven hypersensitivity diseases including severe asthma, allergic bronchopulmonary mycoses, chronic sinusitis, hypersensitivity pneumonitis, atopic eczema/dermatitis syndrome and gut inflammation.…”