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Multiple sclerosis

The blood-brain-barrier and the measurement of de novo central nervous system IgG synthesis

Neurology and Research Services, Wadsworth Veterans Administration Hospital, Los Angeles, CA; and the Department of Neurology, University of California, Los Angeles, CA.

This review deals with the blood-brain-barrier (BBB) as it relates to multiple sclerosis (MS). The MS BBB is discussed in relation to the following: postmortem perfusion utilizing trypan blue; circulating serum albumin as a marker of the normalcy of tight junctions of the endothelium of the CNS; CSF albumin as a marker of the BBB in MS; in vivo detection of an altered BBB of MS lesions utilizing computer tomography of the brain; detection of de novo central nervous system (CNS) IgG synthesis with or without an altered BBB; utilization of a formula to estimate de novo CNS IgG synthesis to evaluate putative therapies. In addition, a proposal is made that there exist within the BBB in MS two interlaced colonies of immunocytes capable of synthesizing IgG in concert or independently. Colony 1 consists of B lymphocytes that may be preprogrammed to antigens experienced by the core immune network, and that are recruited from the blood to the CNS by chemotaxis. This type of immunologic appearance could replicate the MS patient's antigenic exposure and reward the CNS in MS with focal, in situ synthesized antibodies, hence imparting to the CNS an expeditious super-resistance. Colony 2 consists of resident plasma cells attributable to a persistent in situ antigenic stimulation, presumably owing to the MS antigen. Finally, since the CNS in MS has been provoked to become a type of immune organ-that is, it is able to synthesize IgG de novo—it is reasonable to propose the following: That de novo IgG in the CNSKSF, especially oligoclonal IgG, is antibody in excess of its antigen. We believe it can be used as an antibody reagent to search for the persistent antigenic stimulus present most appropriately at the periplaque edge, which might presumably turn out to be related to the cause of MS.

Reprint requests should be addressed to Dr. W.W. Tourtellotte, Neurology Service (1271, VA Wadsworth Hospital Center, Wilshire and Sawtelle Blvds., Los Angeles, CA 90073.

This research was supported in part by research grants from Project 8520-01 VA Central Office funds; National Multiple Sclerosis Society Grant RG 827-C-27; and the Kroc Foundation for the Advancement of Medical Science.

Accepted for publication May 8, 1978.