Review article
The role of antibody affinity for specific antigens in the differential diagnosis of inflammatory nervous system disorders

https://doi.org/10.1016/j.jneuroim.2006.06.033Get rights and content

Abstract

Affinity maturation has previously been shown with assays for total IgG for specific antigens using the technique of competition by chaotropic ions. We have extended this technique to individual clones and followed the maturation of clones during the course of herpes encephalitis. This has important implications for our understanding of the pathogenesis of multiple sclerosis.

Section snippets

General introduction

Antibody affinity has been studied during the course of exposure to various antigens, but is also useful in distinguishing current from previous exposure. These two approaches both rely on the common thread that antibody affinity increases during the maturation of the immune response.

Antibody affinity can be defined as an increase in the bond strength between the antigen and its specific antibodies. This derives from a broad population of antibody molecules, some having higher affinity and

Normal pathophysiology

During the course of exposure to a given antigen, there is a kind of molecular Darwinism in that the best “fit” of various antibodies will “survive” and/or proliferate over the other antibodies and thus along with the classical increase in titres of antibody, there is a parallel increase in affinity. This has been termed “affinity maturation.” For details see paper by Yin et al. (2003).

We have developed a model method based on a commercial antiserum directed against human albumin, since this

Abnormal pathophysiology

The main use in differential diagnosis has been to “titrate” the affinity of antibodies to determine if the exposure to antigen is recent or not. Perhaps the best studied example is that of toxoplasma, where serum derived form the infant contains a mixture of (1) that derived passively from the mother, which is from her prior exposure and is thus of low affinity versus (2) that from the fresh synthesis by the infant, due to the novel exposure, and is thus of high affinity (Buffolano et al., 2004

The future: affinity maturation in individual patients with herpes encephalitis

Using a method that compared the relative affinities of individual clones (Chapman et al., 2006), serial paired samples of serum and CSF (days 1, 6 and 15 after admission) from a patient with confirmed herpes simplex encephalitis (by PCR) were investigated (see Fig. 2).

Day 1 samples showed only a polyclonal pattern of low affinity but the samples from days 6 and 15 both had oligoclonal patterns of high affinity. Antigen-specific IgG in the CSF increased through days 1 to 15 but total IgG

Conclusion

Affinity can play a significant role not only in the diagnosis of MS but also ultimately in helping to unravel its pathogenesis. If multiple sclerosis turns out to be caused by an infectious agent it would be reasonable to hypothesise that the intrathecal oligoclonal IgG that is invariably found in subjects with the disease will react with high affinity to the causative agent.

Cited by (6)

We dedicate this brief review to the memory of Dr. Don Paty, who did much to further our understanding of neuroimmunology, particularly in relation to the continuing enigma of multiple sclerosis.

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