Identification of Different Measles Virus-Specific Antibodies in the Serum and Cerebrospinal Fluid from Patients with Subacute Sclerosing Panencephalitis and Multiple Sclerosis

Abstract

Matched serum and cerebrospinal fluid (CSF) samples from eight cases of subacute sclerosing panencephalitis (SSPE) and 15 cases of multiple sclerosis (MS) were characterized in neutralization, hemolysis-inhibition (HLI), hemagglutination-inhibition (HI) with Tween 80-ether-treated antigen, complement-fixation (CF), and immunodiffusion tests. CF tests were carried out with crude virus material, purified nucleocapsids, and small particle hemagglutinin as antigens. A certain diversity in the relative content of antibodies against different virus products in various sera was found. There was a high degree of correlation between titers of neutralizing and HLI antibodies, but a less strict correlation between titers of HLI and HI antibodies. Serum samples from two cases of MS and one case of SSPE contained high titers of HLI and neutralizing antibodies in the presence of only low titers of HI antibodies demonstrable with Tween 80-ether-treated antigen. The major fraction of antibodies detected in CF and immunodiffusion tests reacted with nucleocapsids. There was a tendency of nucleocapsid CF antibody titers, as compared to neutralization and HLI antibody titers, to be higher in samples from patients with SSPE than from cases of MS. No significant differences were found between antibody titers recorded in neutralization, HLI, and HI tests carried out with two different measles virus strains, Edmonston and a strain (LEC) derived from a case of SSPE. Comparison of antibodies against measles virus products and, as a reference, against a group-specific vertex capsomer antigen of adenovirus in matched serum and CSF samples revealed a production of measles virus-specific antibodies within the central nervous system of all cases of SSPE and 8 out of 15 cases of MS.

Subacute sclerosing panencephalitis

“…85 The ratio of serum titer to CSF titer is lower. 86,87 In many laboratories, measles IgG is measured with the help of standard indirect immunofluorescent assay (IIF) antibody assay technique. In a series of 49 SSPE patients, measles antibody titers (by IIF antibody assay) in serum ranged from 40 to 1280 and in CSF varied from 0 to 32.…”

Intrathecal synthesis of IgG antibodies to varicella‐zoster virus in two cases of acute aseptic meningitis syndrome with no cutaneous lesions

“…Intrathecal production, throughout prolonged follow-up periods, of antibodies of various specificities in patients with SSPE and multiple sclerosis [Salmi et al, 1972;Nordal et al , 1978;Vartdal and Vandvik, 19831 suggests that unspecific stimuli may induce an anamnestic intrathecal synthesis of antibodies to a determined virus. In the cases presented in this paper, which correspond to CNS acute infections of self-limited course, we simultaneously looked in CSF for HSV antibodies, a virus antigenically related to VZV, and mumps virus, a paramyxovirus of known neurotropism.…”

“…The VZV etiology was established by different methods, ie, antigen detection in lymphocytes of the cerebrospinal fluid (CSF) [Peters et al, 19791, complement fixation, or indirect membrane immunofluorescence in serum and/or CSF [Easton, 1970;Gershon et al, 1980;Vilchez-Padilla et al, 19821 or detection of specific oligoclonal antibodies in CSF [Vartdal et al, 19821. The search for virus-specific antibodies in CSF through highly sensitive serological techniques may be applied to the etiological diagnosis of central nervous system (CNS) infections. These methods have been utilized both for the investigation of subacute and chronic neurological processes such as subacute sclerosing panencephalitis (SSPE) or multiple sclerosis [Salmi et al, 1972;Norrby et al, 1974;Kiessling et al, 1977;Nordal et al, 1978;Arnadottir et al, 1982;Vartdal and Vandvik, 19831 and in acute infections, such as mumps meningitis [Friden et al, 1978;Morishima et al, 1980;Ukkonen et al, 19811, encephalitis and ascending myelitis due to herpes simplex virus (HSV) [Lerner et al, 1972;Levine et al, 1978;Kosluniemi and Vaheri, 1982;Kosluniemi et al, 19821, encephalitis, meningoencephalitis encephalomyelitis caused by VZV [Gershon et al, 1980;Vartdal et al, 1982;Andiman et al, 19821, or arbovirus encephalitis [Hoffman et al, 1979;Burke et al, 19821. As far as acute viral infections are concerned, the diagnosis is based on the demonstration that specific antibodies are produced intrathecally .…”

“…This albumin index is considered as the most suitable test for this purpose [Felgenhauer, 19821. 2) Absence of antibodies to other viruses in CSF of the patients and of specific antibodies to the virus in the control patients [Gershon et al, 19801. 3) Antibody levels in CSF clearly in excess of those in serum, when comparing either absolute titers [Salmi et al, 1972;Norrby et al, 1974;Levine et al, 1978;Hoffman et al, 1979;Morishima et al, 1980;Vartdal et al, 19821, total IgG [Ukkonen et al, 19811, or antibody indexes determined in respect to serum and CSF albumin concentrations [Andiman et al, 1982;Arnadottir et al, 1982;Koskiniemi et al, 19821. 4) Detection of specific oligoclonal antibodies in CSF [Norrby et al, 1974;FridCn et al, 1978;Vartdal et al, 1982;Koskiniemi et al, 19821. We describe two patients with an acute meningitis syndrome (AAMS) with no cutaneous lesions or a recent history of varicella or zoster clinically apparent who exhibited, in CSF, VZV antibodies of intrathecal origin according to some of the previously mentioned criteria.…”

Detection of Measles Antibodies in Cerebrospinal Fluid and Serum by a Radioimmunoassay

“…Specific measles virus antibodies can also be detected in cerebrospinal fluid (CSF) obtained from MS patients, and a similar variation in antibody response to individual mea-2 sles components is found in this fluid (17). From several kinds of evidence, it appears that these antibodies result, at least in part, from local synthesis within the central nervous system (CNS) (4,11).…”