An Introduction to Intravenous Immunoglobulins and Natural Autoantibody

Human plasma is rich in a variety of antibodies including IgA, IgM, and IgG antibodies. Concentrated antibodies, known as intravenous immunoglobulins (IVIG), can be obtained from plasma by physical separation. IVIG contains a small amount of natural autoantibody.

Natural autoantibody (NAA), is a seminal part of the immune system originating from B1-cells and is mainly of the IgM isotype, with generally low binding affinity. They play important and diverse immunological roles, providing very early innate immune protection, ensuring removal of possible autoantigens by scavenging dead or apoptotic cellular debris, and possibly also improving cardiovascular profile.

This article will briefly introduce the current research and development trend of IVIG and NAA, and the comparisons between them.

The FDA (U.S. Food and Drug Administration) and EMA (European Medicines Agency) have approved IVIG for clinical use. The low dose is indicated for the treatment of people with antibody deficiency, secondary hypovolemia, and recurrent bacterial infections. High doses are indicated for autoimmune diseases and infections, including idiopathic thrombocytopenic purpura, Kawasaki disease, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. In addition, IVIG can be used clinically for more than 70 different disorders, including hematologic, dermatologic, and neuromuscular disorders. Clinical trials have also shown that IVIG may have anti-tumor growth and metastatic effects, and some studies have suggested that IVIG is a potentially useful adjuvant in anticoagulant therapy.

While NAAs are characterized by low affinity, non-specificity, and low chemotaxis. Early recognition of NAA was mainly based on IgM antibodies of ABO blood groups. With the development of science and technology, it has been found that NAAs also include IgG and IgA. Anti-VEGFR natural IgG antibodies have been found to inhibit the growth of cancer cells by inhibiting vascular endothelial growth factor receptor (VEGFR1), including liver cancer, pancreatic cancer, and nasopharyngeal cancer.

The characteristics of IVIG compared to anti-tumor NAA plasma are as follows.

1. They both present the risk of infection with blood diseases as they are derived from human plasma.
2. The affinity and specificity of them are both at a low level, and there are more adverse reactions with IVIG.
3. The batch variability in the production of IVIG and NAA plasma is relatively high.
4. The therapeutic effect of anti-tumor NAA plasma is yet to be evaluated. There is too little information on clinical trials.
5. It is very difficult to screen a large amount of anti-cancer NAAs from plasma as the percentage of people carrying these antibodies is extremely low. The targets currently used are not the most researched mature targets, and it is uncertain whether they will be effective in patients with advanced hepatocellular carcinoma and patients with metastatic tumors.

Over the past two decades, IVIg has become the preferred treatment for Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and Kawasaki disease. While the application of NAA in clinical treatment is still on the way. With the increasing understanding of the physiology of NAAs, scientists are exploring how to harness NAAs as a future therapy for autoimmune disorders.

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