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Why antibodies disobey the Hippocratic Oath and end up doing harm: a new clue
Liise-anne Pirofski
Liise-anne Pirofski
Published August 25, 2010
Citation Information: J Clin Invest. 2010;120(9):3099-3102. https://doi.org/10.1172/JCI44312.
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Commentary

Why antibodies disobey the Hippocratic Oath and end up doing harm: a new clue

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Abstract

The appearance of methicillin-resistant Staphylococcus aureus (MRSA) as an endemic microbe, first in hospital and health care settings and more recently in the community, has led to a disastrous situation in which use of the available antibiotic armamentarium is increasingly ineffective and spawns further antibiotic resistance. This vicious cycle highlights the pressing need for an S. aureus vaccine. However, to date, clinical trials with S. aureus vaccines have not demonstrated sustained efficacy. In this issue of the JCI, Skurnik and colleagues report that specific antibodies to two different S. aureus surface polysaccharides, which independently promote effector cell killing of S. aureus in vitro and protection against S. aureus in animal models, bind to and abrogate the activity of one another when they are combined. This fascinating finding suggests a new paradigm to explain the failure of antibody immunity to S. aureus.

Authors

Liise-anne Pirofski

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Figure 2

How antibodies specific for one polysaccharide could produce antibodies that bind another.

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How antibodies specific for one polysaccharide could produce antibodies ...
(A) Immunization with an antigen elicits antibodies that are specific for that antigen. This is depicted for S. aureus CP and dPNAG. (B) If the antigen-binding site (idiotype) of one antibody (Ab1) elicits an anti-idiotype response, the resulting antibody (Ab2) will bind Ab1, forming an idiotype–anti-idiotype complex. This is shown for an antibody specific for dPNAG that elicits an antibody that could bind CP. If the anti-idiotypic antibody (Ab2) elicits another anti-idiotypic antibody (Ab3), it could have the same binding characteristics as Ab1 and bind dPNAG. A similar scenario could occur for antibodies specific for CP. (C) If the antigens have determinants that are mirror images of (or complementary to) one another, they could independently elicit antibodies that bind one another.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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