Properties and action mechanisms of intravenous gammaglobulin

Núria Matamoros Flori

doi:10.11606/issn.2176-7262.v47i1p16-19

Abstract

Intravenous immunoglobulins (IVIG) preparations have been used as a substitutive therapy for primary and secondary immunodeficiencies for many years; now it is well know that IVIG can have two other important and opposite functions: pro and anti-inflammatory, depending on its concentration. Low doses of IVIG exert proinflammatory activities, that require complement activation or binding via Fc fragment of IgG to IgG Fcγ specific receptors present on effector cells of innate immunity. On the other hand, administration of high IVIG doses has anti-inflammatory activity. This manuscript presents a revision of how IVIG IgG mediated this effects, how and upon which cells from the immune system acts, their capacity to scavenging complement fragments, the recently demonstrated anti-inflammatory activity of variable minor sialylated portion of IgG molecules and finally, the importance of genetic variation and expression of Fcγ receptors. To comprehend the mechanism of action of IVIG is fundamental, not only to obtain further improvements on therapeutic effectiveness, but also to discover new and unexpected capacities of this biological bomb known as IVIG.

Highlights

Human immunoglobulin was used for the first time in 1950 as a substitutive therapy in a patient with primary agammaglobulinemia.[1]
Several mechanisms could explain the anti-inflammatory activity of IVIg, but the most relevant contributor to this activities are the Fc fragments of IgG.[5,6]
Recent observations demonstrated the effects of Intravenous immunoglobulins (IVIG) therapy on different cells of the immune system, dendritic cell (DC), monocyte/macrophages, granulocytes, natural killer (NK) and T and B lymphocytes, belongins to adaptive as well as in innate immune responses.[7]

Summary

Introduction

Human immunoglobulin was used for the first time in 1950 as a substitutive therapy in a patient with primary agammaglobulinemia.[1] It was not until the 1980s when improvements on the plasmatic fractioning allow to develop molecules with an intravenous use (IVIG), allowing a much larger amount of infusion and a wider therapeutic role than the IDP, applied, as well, in an important number of autoimmune diseases, inflammatory disorders and a wide range of off-label indications.[2] Gamma globulin is made from human plasma and its production is limited, affecting its price and making it an expensive good. Dra. Núria Matamoros Florí Cap de Servei d’Immunología Hospital Universitari Son Espases. Nowadays we know the importance of pro and anti-inflammatory effects of gammaglobulin depending on the applied use

Activities of IVIG

Impact of IVIG on immune function

Conclusions