Comparison of agar gel electrophoresis and isoelectric focusing in multiple sclerosis and subacute sclerosing panencephalitis

Abstract

Isoelectric focusing (IEF) and agar gel electrophoresis (AGE) were used to examine cerebrospinal fluid (CSF) and sera from patients with multiple sclerosis (MS) and subacute sclerosing panencephalitis (SSPE). All 15 SSPE samples and 29 of the 33 MS CSF samples showed oligoclonal IgG bands by AGE and IEF. Serum bands were more frequent in SSPE than in MS and were more commonly detected by IEF than by AGE. In MS CSF the number of bands on IEF correlated with: (1) disease duration, (2) CSF IgG, (3) CSF IgG/albumin ratio, and (4) central nervous system IgG synthesis. Serial studies revealed increases in IEF band number in 4 of 10 MS and 3 of 5 SSPE CSF specimens; fluctuations in band intensity were also noted. Densitometric scans of CSF IEF gels showed high, sharply angled IgG band peaks in SSPE; the CSF band peaks in MS were flatter and had higher background IgG. The SSPE pattern could be made to resemble the MS pattern through addition of normal polyclonal IgG to SSPE CSF. These findings suggest that in addition to oligoclonal IgG, polyclonal IgG is synthesized locally within the central nervous system in MS.

Evidence of an immunopathogenic basis for central nervous system disease in primary Sjögren's syndrome

“…CSF and serum albumin and IgG concentrations were measured simultaneously by radial electroimmunodiffusion (30). The CSF IgG index was calculated by the formula: (CSF IgGlCSF albumin)/(serum IgGherum albumin) (16,17). CSF IgG indices 20.7 were considered abnormal (16) and indicative of endogenous production of IgG within the CNS.…”

“…CSF IgG indices 20.7 were considered abnormal (16) and indicative of endogenous production of IgG within the CNS. The CSF albumin x 103:serum albumin ratio (Q albumin), a measure of blood-brain barrier integrity, was considered abnormal when it was >9 (16,17). The degree of blood-brain barrier impairment was graded according to the method of Schliep and Felgenhauer (31) Control samples consisted of normal CSF, CSF from a patient with classic multiple sclerosis (MS) (which produced oligoclonal bands), and serum from a patient with multiple myeloma (which consistently produced 2 discrete bands in the gamma globulin region (Figure 1).…”

“…An elevated IgG index has been established as a reliable indicator of the intrathecal production of IgG (14,15), particularly in the presence of an intact blood-brain barrier (16). The use of agarose gel electrophoresis has led to the description of specific qualitative abnormalities of immunoglobulin, and these consist of restricted bands of protein, each representing immunoglobulin secreted by individual clones of B cells (17,18). Such CSF immunoglobulin abnormalities have been observed in several autoimmune neurologic diseases (19), and most recently in CNS disease associated with systemic lupus erythematosus (SLE) (20,21), in which immunemediated pathogenic mechanisms are implicated.…”

Antigen Discovery in Chronic Human Inflammatory Central Nervous System Disease: Panning Phage-Displayed Antigen Libraries Identifies the Targets of Central Nervous System-Derived IgG in Subacute Sclerosing Panencephalitis

“…OGBs are also present in the brains of several inflammatory CNS diseases of unknown cause, such as multiple sclerosis (MS) and CNS sarcoidosis. Although OGBs are found in 88 -100% of CSF from MS patients, their corresponding Ags are unknown (1,20). We predict that identification of the antigenic targets of the OGBs will help to understand the pathogenesis and even the cause of these diseases.…”

Sequential changes in oligoclonal patterns during the course of multiple sclerosis.

“…Thus antigens which can absorb the greater part of the oligoclonal bands have not been found. 4 Furthermore, the most widely held view (for example Bloom,5 Norrby,2 Lisak6) is that once established, the particular pattern of oligoclonal bands found in the CSF of any individual patient, remains the same at subsequent examinations.378 The pattern persists, as it were, like a "fingerprint" although there may be changes in density of individual bands. In contrast, our findings show that changes do occur in the oligoclonal patterns on polyacrylamide electrophoresis of unconcentrated CSF from 25 patients with multiple sclerosis studied longitudinally.…”