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To study the permeability of the blood-brain barrier (BBB) and the blood-nerve barrier (BNB) for immunoglobulin G (IgG) we adapted the avidin-biotin system for postembedding demonstration of the tracer IgG in the central and peripheral nervous system (CNS, PNS). Normal mouse and human IgG were biotinylated and injected daily into the intraperitoneal (i.p.) space of adult BDF1 mice. After 24h, IgG was detected in blood vessels and in the interstitium of various organs, but staining was restricted to the dura mater in the CNS, to the spinal ganglia, and to the perineurium of peripheral nerves. After 4 days, IgG was also present in the endoneurial connective tissue of peripheral nerves, while the brain, spinal cord, and spinal roots remained free of IgG. Our results show a partial permeability of the normal mouse BNB for homologous and heterologous IgG.

In chronic (relapsing) inflammatory polyneuropathy (CRIP), successful treatment with plasma exchange has led to the concept of pathogenic humoral factors. In 6 patients with CRIP, 5 of whom improved after plasma exchange, the potential pathogenic role of circulating immunoglobulin (Ig) fractions was tested by applying the systemic passive transfer model to marmoset monkeys. After continuous treatment with intramuscular injections for 2-8 weeks, monkeys injected with the crude immunoglobulin fractions or with purified IgG from 5 of the 6 patients showed a significant and partially reversible reduction of the motor nerve conduction velocity (mean 34%, P less than 0.001) when compared with pre-treatment values. In control animals the reduction was 4%. Morphological examination revealed only minor ultrastructural changes of the myelin sheath. Immunocytochemistry revealed that human IgG was able to cross the blood-nerve barrier. It is concluded that the circulating IgG-fraction of patients with CRIP contains a factor that may contribute to the disordered nerve function after crossing the blood-nerve barrier. It may be the removal of this particular factor which is responsible for the rapid recovery of nerve conduction in patients after plasma exchange.

The capacity of the avidin-biotin system for post-embedding cytochemical detection of a biotin-labeled proteinaceous tracer was investigated. By testing modifications of the fixatives, the epoxy embedding medium, and various etching solutions, a procedure was developed to localize specifically the biotinylated tracer on 1-micron thick and thin sections. By use of this technique, a systemically administered IgG tracer was demonstrated after 24 hr throughout the endomysium of mouse skeletal muscle. In the adjoining sciatic nerve, the tracer IgG occurred at the perineurium and within endoneurial blood vessels, although the endoneurium itself was spared because of the presence of the blood-nerve barrier. Because of the small size of the biotin ligand and the non-denaturing method of labeling proteins, our mode of application of the avidin-biotin system appears suitable for tracer studies.