Chapter Details

Pub Date: 16 Apr 2012
Pages: 12
Chapter Category: Autoimmunity
Taken from the Book: Naturally Occurring Antibodies (NAbs)
Book Series: Special Books
Edited by: Hans U. Lutz

Download PDF

All chapters PDFs are available for free under an Open Access license.

Naturally Occurring Antibodies as Therapeutics for Neurologic Disease:
Can Human Monoclonal IgMs Replace the Limited Resource IVIG?

Arthur E. Warrington, Virginia Van Keulen, Larry R. Pease and Moses Rodriguez

About this Chapter

Naturally occurring autoantibodies (NAbs) are common in normal humans. The majority of NAbs are IgMs, but a small proportion are IgGs. Therefore a certain portion of pooled whole human IgG (IVIG) can be considered NAbs. While the applications of IVIG to modulate human disease have increased dramatically, the use of IgMs as drugs has lagged. In fact, much of the contaminating IgM component of IVIG is disposed of as waste. However, a number of model studies, including those targeting Alzheimer and multiple sclerosis (MS) suggest that IgMs may better modulate disease at much lower doses than IVIG. Our own studies in a model of MS show that polyclonal human IgM promotes better remyelination than IVIG and that monoclonal IgMs promote greater remyelination than monoclonal IgGs containing identical variable region sequences. We propose that this difference is due to the ability of IgM to cross link cell surface antigens better than IgGs and induce signals in nervous system cells. Monoclonal antibodies (mAbs) that promote remyelination induce a transient Ca2+ influx in myelin forming cells, whereas IgGs with identical variable sequences do not. MAbs that promote remyelination were identified in human serum and in EBV‑immortalized human B‑cell lines obtained from normal adults, fetal cord blood, and rheumatoid arthritis and MS patients. Therefore therapeutic mAbs are present and common in normal circulation. All therapeutic mAbs were IgMs and bound to nervous system cells, however, the tissue binding patterns suggest that binding any one of multiple antigens induces repair. An expression vector was constructed that can manufacture gram quantities of recombinant monoclonal human IgM. Therefore the technology exists to determine whether human monoclonal NAbs can modulate human disease. IVIG can modulate neurologic disease, but using IVIG to treat these chronic diseases is unsustainable. A long‑term solution is to identify the functional component of IVIG and test whether a recombinant human monoclonal can replicate its efficacy.

More chapters from the book

Ischemia and reperfusion events within the heart and brain and similar trauma‑induced ischemia/reperfusion events lead to significant morbidity and mortali...

Polyspecificity (polyreactivity) is currently considered an intrinsic property of a subset of antibodies, primarily of naturally occurring autoantibodies. Po...

Germline‑encoded naturally occurring autoantibodies (NAbs) developed about 400 to 450 million years ago to provide specificity for clearance of body waste ...

Subsets of IgM naturally occurring autoantibodies (NAbs) bind to the cell surface membranes of dying cells. The antibodies predominantly have specificities a...

Naturally occurring autoantibodies (NAbs) are common in normal humans. The majority of NAbs are IgMs, but a small proportion are IgGs. Therefore a certain po...

Healthy persons carry within their pool of circulating antibodies immunoglobulins preferentially of IgM isotype, which are directed against a variety of tumo...

Naturally occurring antibodies (NAbs) have specificity for both microbial and self antigens, which allows them to act in the first line defense against invad...

Programmed cell death (PCD) plays a central role in the regulation of granulocytes that are key effector cells of the innate immune system. Granulocytes are ...

Naturally occurring antibodies (NAbs) play a vital role in the first line of defense against bacterial and viral infections. Most studies in mice and man hav...

Antibody networks have been studied in the past based on the connectivity between idiotypes and anti‑idiotypes—antibodies that bind one another. Here we ...

The role of naturally occurring autoantibodies (NAbs) in homeostasis and in disease manifestations is poorly understood. In the present chapter, we review ho...

Naturally occurring autoantibodies (NAbs) are typically polyreactive, bind with low affinity to a discrete set of autoantigens and are encoded by variable re...

Most studies on the effects of naturally occurring autoantibodies (NAbs) on immune cells have been performed in the context of research on the immunomodulato...

In sepsis death follows an excessive inflammatory response involving cytokines and complement that is activated primarily via the amplifying C3/C5 convertase...

Immunoglobulins (antibodies) frequently express constitutive functions. Two such functions are nucleophilic catalysis and the reversible binding to B‑cell ...

Naturally occurring antibodies (NAbs) have been described for more than 30 years. Recently, NAbs against β‑Amyloid and against other proteins involved in ...

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 hum...

Naturally occurring antibodies (NAbs) produced by CD5+ B‑1 B cells include those with specificity for thymocytes (anti‑thymocyte autoantibody, ATA). Here...