The Clinical Translation of Intravenous Immunoglobulin from Substitution to Immunomodulation

Abstract

This introductory chapter describes how the training of young investigators by experienced mentors can lead to translation of chance observations within practical clinical science. Substitutive administration of a new concentrate of a human immunoglobulin (IgG) preparation resulted in regular minimal platelet increases in a child with a primary immunodeficiency and low platelet counts despite normal platelet production. The investigators concluded that this phenomenon might also be possible in children with immune thrombocytopenia (ITP). This translation became a reality, first by a pilot study comparing children with ITP versus aplastic anemia with disturbed platelet production, followed by a confirmatory study, where children with newly diagnosed or chronic ITP consecutively showed dramatic platelet increase by IgG administration, and, later, by a controlled randomized cooperative study in children with ITP. Since the pathophysiology of ITP is similar to many other autoimmune or chronic inflammatory disorders, the new therapeutic phenomenon evoked worldwide clinical and laboratory research. The story is presented with citations of the first publication.