Measles Virus Antibody Titers Research Articles

Utility of enzyme immunoassays for diagnosis of subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a progressive neurologic disorder caused by the measles virus (MV) and is identified by positive MV-specific antibody titers, detected mainly by hemagglutination inhibition (HI) tests in the cerebrospinal fluid (CSF). However, an alternative method, the enzyme immunoassay (EIA), has increasingly become a preferred method for detecting MV antibodies. To establish the index for SSPE diagnosis using EIA, we investigated the correlation between HI and EIA titers of MV antibodies in SSPE patients. Data on MV antibody titers and measurement methods at the time of diagnosis in 89 Japanese SSPE cases diagnosed between 1979 and 2006 were obtained by a survey. We also assessed the serum and CSF MV antibody titers in three patients with SSPE and serum MV antibody titers in 38 healthy adults using immunoglobulin G (IgG)-EIA and HI. In all cases diagnosed as SSPE, IgG-EIA titers in the CSF were ≥0.49IU/mL. There was a positive correlation between serum antibody values in the controls measured by IgG-EIA and HI. In patients with SSPE, both serum and CSF antibody values, measured by IgG-EIA, and HI, were positively correlated, and a positive correlation was found between the serum and CSF MV antibody titers as measured by IgG-EIA. The serum/CSF MV antibody titer ratios determined by IgG-EIA were <20 in most SSPE patients. Immunoglobulin G-EIA may be a suitable alternative method for SSPE diagnosis; however, its potential utility and the cut-off point of ≥0.49IU/mL should be tested with additional patient cohorts.

Measles Virus Neutralizing Antibodies in Intravenous Immunoglobulins: Is an Increase by Revaccination of Plasma Donors Possible?

We report a screen of plasma donors confirming that widespread use of childhood measles vaccination since 1963 resulted in a decrease in average measles virus antibody titers among plasma donors, which is reflected in intravenous immunoglobulins (IVIGs). The measles virus antibody titer, however, is a potency requirement for IVIGs, as defined in a Food and Drug Administration regulation. To mitigate the decline in measles virus antibody titers in IVIGs and to ensure consistent product release, revaccination of plasma donors was investigated as a means to boost titers. However, revaccination-induced titer increases were only about 2-fold and short-lived.

Comparison of neutralizing antibody titers against outbreak-associated measles genotypes (D4, H1 and B3) in Iran.

Despite the accessibility of a promising vaccine, outbreaks of the measles virus (MV) take place even in well-vaccinated populations. D4, H1 and B3 genotypes have been detected regularly in different regions of Iran. These observations highlight the necessity of evaluating the protective efficacy of the vaccine against currently circulating MV genotypes during the elimination phase. A focus reduction neutralization test has been developed to measure the neutralizing antibodies against different genotypes of MV, such as H1, D4, B3 and vaccine strain (A), in children after second doses of measles vaccine. The geometric mean titer (GMT) rates of the sera against D4, H1, B3 and A genotypes were 95.9, 90.5, 32.0 and 76.1, respectively. Low GMTs of antibody against the B3 genotype compared with the other genotypes were indicated. Based on the current study results, the MV antibody titers in the sera of vaccinated cases are sufficient to neutralize all circulating genotypes in Iran; however, neutralizing antibody titers were lower for the B3 genotype than for the H1, D4 and A genotypes. The heterogeneous nature of MV, for instance the nucleotide sequence diversity between different strains, necessitates the evaluation of the protective efficacy of the vaccine against measles B3 genotype in countries where this virus has been the most commonly identified circulating genotype.

Similar Antibody Levels in 3-Year-Old Children Vaccinated Against Measles, Mumps, and Rubella at the Age of 12 Months or 18 Months.

Measles-mumps-rubella (MMR) vaccinations have been offered to Finnish children at 14-18 months and 6 years of age. In May 2011, the recommended age for the first vaccine dose was lowered to 12 months because of the European measles epidemic. Fingertip capillary blood samples were collected from 3-year-old Finnish children vaccinated once with MMR vaccine at 11-19 months of age. The immunoglobulin G (IgG) antibodies to all 3 MMR antigens were measured with enzyme-linked immunosorbent assay. Neutralizing antibodies and the avidity of antibodies were measured for measles virus. From April through October 2013, 187 children were enrolled. Equally high proportions of the samples were seropositive for measles virus, mumps virus, or rubella virus antibodies, and there were no significant differences in the IgG antibody concentrations in children vaccinated at 11-13 months of age, compared with those vaccinated at 17-19 months of age. However, among children vaccinated at 11-13 months of age, boys had lower antibody concentrations than girls. Neutralizing measles virus antibody titers were above the threshold for protective immunity in all 78 samples analyzed. The measles virus antibody avidity indexes were high for all children. MMR induces similar antibody responses in 12-month-old children as compared to 18-month-old children, but in boys increasing age appears to improve the antibody responses.

Genetic basis of multiple sclerosis: HLA antigens, disease progression, and oligoclonal IgG in CSF.

The HLA antigens B7 and Dw2 occurred at elevated frequencies in 105 multiple sclerosis (MS) patients (49 and 47%, respectively), compared to healthy controls (29 and 30%), especially in MS patients with oligoclonal CSF-IgG (51 and 50%), in cases with CSF-IgG index values above 1.5 (64 and 64%), and in those with the most malignant course of the disease (47 and 59%). Normal or only slightly elevated frequencies of B7 and Dw2 were found in MS patients without oligoclonal CSF IgG (35 and 29%), normal CSF-IgG index (43 and 39%), and the most benign course (42 and 37%). No correlation was found between the HLA type and measles virus antibody titers in serum or a measles virus antibody response within the CNS.

Immunoglobulin G subclass antibodies to measles virus in patients with subacute sclerosing panencephalitis or multiple sclerosis.

Mouse monoclonal antibodies specific for human immunoglobulin G (IgG) subclasses and a sensitive immunoassay were used to evaluate the IgG subclass antibody response to measles virus antigens in cerebrospinal fluid and serum samples from 20 patients with subacute sclerosing panencephalitis (SSPE), 12 patients with multiple sclerosis (MS), and 11 controls with high measles virus antibody titers in serum. In patients with SSPE, measles virus-specific antibodies were found mainly in the IgG1 subclass and the IgG subclass distribution remained unchanged, irrespective of the clinical stage or duration of the disease. In patients with MS and in controls, measles virus activity was also associated mainly with IgG1. However, the activity was significantly lower than that found in patients with SSPE. The results suggest that there is no primary abnormality in humoral immune response to measles virus in patients with MS. The disproportionately high levels of the measles virus-specific IgG1 subclass found in patients with SSPE may be due to persistent antigenic stimulation or reflect a defect in immunoregulatory mechanisms in response to viral infection.

Clinical effects of MND-19 (Inosiplex) on subacute sclerosing panencephalitis: — A multi-institutional collaborative study—

A total of 151 cases of subacute sclerosing panencephalitis (SSPE), comprising 89 cases treated with MND-19 (Inosiplex) and 62 untreated cases, were retrospectively investigated as to background characteristics, survival rate and clinical course in order to compare the findings in the 2 groups of cases. The survival rate for the cases treated with MND-19 (MND-19-treated group) was significantly higher than that for the untreated cases (control group), which was also true on stratified analysis or on smoothing of the background factors by means of Cox's multiple regression model. Investigation of the clinical course revealed that progression through the disease stages was significantly slow in the MND-19-treated group, compared with in the control group. Global rating of the clinical course showed that a prolonged remission was obtained in more MND-19-treated cases than control cases. The measles virus antibody titer was in no way affected in the former group. Side effects of MND-19 were observed in 17 of the 89 treated cases (19.1%).

Measles and canine distemper virus antibodies in patients with multiple sclerosis determined by radioimmunoassay.

Antibodies against measles virus (MV) and canine distemper virus (CDV) were measured by solid-phase radioimmunoassay (RIA) of sera and cere-brospinal fluid (CSF) from 28 patients with multiple sclerosis (MS) and matched neurological controls. When the groups were compared for MV antibody titers and CDV antibody titers of sera and MV/CDV serum antibody titer ratios, no significant difference was found. The CDV antibody titers and the MV antibody titers were in good correlation. CDV antibodies showed RIA titration curves typical of low avidity antibodies. In tests for MV antibodies in CSF, 82% of the MS patients and 19% of the controls were positive, whereas 36% of the MS patients and 4% of the controls were positive in CDV RIA. The correlation between MV and CDV antibody levels, the low avidity of CDV antibodies and the fact that absorption of the specimens with MV antigen abolished all CDV antibody activity suggest that the CDV antibodies are MV antibodies cross-reacting with CDV. It is concluded that canine distemper virus is unlikely to be involved in the etiology of multiple sclerosis.

Augenbefunde bei der subakut sklerosierenden Panenzephalitis

A report is given on 10 children with subacute sclerosing panencephalitis (SSPE) whose clinical illness began with visual or mental impairment. All patients showed typical clinical and neurologic features and various ophthalmological manifestations. The latter correspond to lesions generally dealt with in a number of reports and demonstrate for the individual case that ophthalmological manifestation can precede clinical manifestation. The ophthalmologist can give an important contribution to the diagnosis. In some cases the focal retinal lesions can be similar to retinal lesions in the case of toxoplasmosis. A positive antibody titer for toxoplasmosis, which can occur parallel with the typical measles or SSPE virus antibody titer, occasionally causes the misdiagnosis of toxoplasmosis acquisita. In the 10 cases reported on, the diagnosis SSPE was confirmed on the basis of the typical clinical features and elevated measles virus antibody titer. In no case the permission for autopsy was gained. The genesis of SSPE is discussed with reference to a genetic defect, to an autoimmune reaction, or as a result of a measles virus-like infection. In the diagnosis, primarily unclear 'focal retinal lesions' should be at any rate investigated with respect to measles or SSPE virus antibody titer.

Immune enhancement of the tumorigenicity of hamster brain tumor cells persistently infected with measles virus

Studies were conducted on the tumorigenicity of a hamster brain tumor (HBT) cell line persistently infected with measles virus (MV). This cell population, termed HBT-M, exhibited decreased tumorigenicity in weanling hamsters when implanted intracutaneously. The lowered tumorigenicity of the HBT-M cells could be counteracted by concurrent hydrocortisone treatment restoring the tumor-producing capacity to levels comparable to those of the highly tumorigenic HBT cells. It was also determined that prior immunization of hamsters with MV resulted in enhancement of tumor formation from usually subtumorigenic doses of HBT-M cells. This increase in tumorigenicity appeared to correlate with high titers of MV antibody. Treatment of hamsters with cyclophosphamide resulted in a reduction of MV antibody titers and effected a decrease of HBT-M cell tumorigenicity to control levels. Preliminary studies with passive immunizations indicated that the enhancing factor could be transferred in the sera from hamsters hyperimmunized with MV. These data suggested that MV antibody may potentiate the development of neoplasia of cells persistently infected with MV in a manner similar to the enhancement of tumor growth by blocking antibody.

The relationship between measles virus-specific antibodies and oligoclonal IgG in the cerebrospinal fluid (CSF) in patients with subacute sclerosing panencephalitis (SSPE) and multiple sclerosis (MS)

A comparison of measles virus antibody titers in sera and CSF samples has demonstrated that antibodies appearing in the latter type of samples are locally produced in the central nervous system in all patients with SSPE and in about 60% of patients with MS. The relationship between these locally produced measles virus antibodies and the oligoclonal IgG in patients with these diseases was studied by use of two different techniques. One technique was to absorb concentrated CSF with purified measles virus particles to analyse their capacity to remove oligoclonal IgG. Antigen-antibody complexes formed were isolated by sedimentation whereafter IgG was eluted at pH levels of 4.0, 3.0 and 2.0. The second technique was to make a preparatory electrophoresis of concentrated CSF and then to analyse the distribution of antibodies against different measles virus antigens in fractions collected. In the case of SSPE repeated absorbtions with measles virus antigens caused an almost complete removal of all oligoclonal IgG. After preparatory electrophoresis peaks of antibody activities correlated in their electrophoretic position to the occurrence of bands of oligoclonal IgG. Different bands were interpreted to carry different antibody activities. Results of studies of materials from MS patients differed somewhat from those obtained in characterization of materials from SSPE patients. Only in exceptional cases could absorption with purified virus particles modify the band pattern of oligoclonal IgG and generally absorption with measles virus antigens in the selected cases did not influence the level of IgG in the samples. However in low pH eluates measles virus antibody activities and a few bands of oligoclonal IgG were recovered. Preparatory electrophoresis of concentrated CSF material from MS patients resulted in a varying distribution of antibodies against different measles virus antigens but a distinct correlation between accumulation of antibody activity and bands present in the electropherogram could not be discerned