Naturally Occurring Antibodies/Autoantibodies in Polyclonal Immunoglobulin Concentrates

Abstract

It was a long way from the use of hyperimmune animal sera for the treatment of toxin-producing infections to the production of polyclonal, polyspecific human immunoglobulin preparations and the use of NAbs as therapeutic tools for autoimmune and inflammatory diseases. Some highlights of the development of knowledge in blood fractionation techniques, basic science and clinical wisdom are reviewed in this chapter. Proudly we mention the outstanding contribution of Swiss scientists and clinicians in the development of IVIG as clinical tool for some otherwise untreatable diseases or taking advantage of its low adverse event profile in long-term treatment of other chronic autoimmune and inflammatory diseases. This chapter summarizes some of the characteristics and the effects in humans of NAbs which are present in IgG concentrates. We call attention to the fact that the human data remain, at least in part, incomplete, among others because even with the most efficient large-scale techniques available not more than approximately 50% of the total IgG in plasma can be fractionated into an immunoglobulin G concentrate.

On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

“…Three facts have initiated our thinking about possible consequences of removal of histo-blood group A and B reacting antibodies from IgG concentrates. (I) In collaboration with Hans U. Lutz, formerly Biochemistry ETH Zurich, we have observed the non-intended removal of natural anti-C3 autoantibodies regulating complement activation by large-scale immune-affinity adsorption of IgA from an IgG concentrate ( 129 ). Anti-C3 antibodies belong to the family of “NAbs” and have a particular role in homeostasis: they control activation of complement, among others, in the frame of NAb-mediated opsono-phagocytosis of altered or senescent cells, including RBCs ( 130 – 132 ).…”

A glance on recent progresses in diagnosis and treatment of primary immunodeficiencies/ Progrese recente în diagnosticul şi tratamentul imunodeficienţelor primare

“…IgG concentrates derive from the immune system of several thousand healthy donors. Their application in patients results in the desired recognition and subsequent removal of possible pathogens but inevitably also results in the recognition of the recipient's variable-region connected immune network (75) and the recognition of altered or senescent tissue in an alloimmune fashion (76). This type of adverse events, as a consequence, is more patient than product dependent.…”

Encoding the Sequence of Specific Autoantibodies Against beta-Amyloid and alpha-Synuclein in Neurodegenerative Diseases

“…The first involves purification of nAbs from commercially available intravenous class G immunoglobulins (IVIg), which is already being used for a variety of neurological diseases, such as myasthenia gravis and multiple sclerosis (17, 18). However, IVIg is a limited and expensive resource, as its preparation is dependent on blood donations (19). A second possibility is recombinant production.…”