The Current Status of Multiple Sclerosis Intra‐Blood‐Brain‐Barrier IgG Synthesis

Abstract

The status of the central nervous system as an immunologic organ synthesizing IgG in several neurological diseases has been established convincingly in the past two decades. The measurement of intra-BBB IgG synthesis has been accomplished. It has been demonstrated that this synthesis is a potential marker for an abnormal immunologic process within the CNS which if manipulated may be a quantifiable aspect of disease modulation. Modulation of intra-BBB IgG synthesis is feasible, but there is no evidence yet that modulation of this synthesis is an index of effective disease control in MS. Only ACTH and corticosteroids lead to a significant and lasting depression of intra-BBB IgG synthesis, even though clonal eradication is not achieved. Based on our immunopharmacologic studies in MS we have proposed an immunokinetic model. The qualitative analysis of the specificity of IgG synthesized intra-BBB in MS has not led to the etiology of MS, but utilization of quantitative methods may. Questions raised by this review with suggested experiments to advance further our understanding of intra-BBB IgG synthesis as it relates to the etiopathogenesis of MS are included.

Cerebrospinal Fluid Biochemistry in the Diagnosis of Multiple Sclerosis

“…Tourtellotte et al 6 reported similar findings with CSF bands present in nearly 100% of clinically definite cases. The presence of raised IgG synthesis is taken as alternative evidence but, whereas bands were detected in 23/24 (96%) of our cases of clinically definite or probable MS, only 17 out of24 (71%) had an increased % IgG.…”

Intracerebral Recruitment and Maturation of Dendritic Cells in the Onset and Progression of Experimental Autoimmune Encephalomyelitis

“…This may be further promoted by cytokines, like granulocyte-macrophage colony-stimulating factor, tumor necrosis factor, and interleukin-1, produced intracerebrally during EAE. 44 -46 The establishment of DC T and B cell interactions within the CNS parenchyma could sustain the intrathecal B-cell clonal expansion typically associated with multiple sclerosis 47 and the production of anti-myelin antibodies detected in EAE and multiple sclerosis lesions. 17 Mature intracerebral DCs are also likely to secrete chemokines contributing to the recruitment of additional DCs, CD4 ϩ and CD8 ϩ T cells to the inflamed CNS.…”

Interferon-β Treatment for Multiple Sclerosis

“…4 Early work profiling the immune response in the CSF of MS patients determined that the antibody response resembled that seen in response to a viral infection. 5 Although no causative virus was identified, it was known that endogenous lymphocyte interferon production was deficient in MS, 6 leading to the idea that exogenously delivered interferon might correct this deficit. Interferon was postulated to reduce IgG synthesis through a direct effect on plasma cells, while simultaneously modulating natural killer cell activity.…”