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1.
The immune response to matrix (M) protein of measles virus was examined in patients with subacute sclerosing panencephalitis (SSPE) and controls. Antibodies specific for M and nucleocapsid (NC) proteins in 11 serum and 8 cerebrospinal fluid (CSF) samples from patients with SSPE were quantitated by enzyme-linked immunosorbent assay by using affinity-purified measles virus proteins. Geometric mean anti-NC antibody titers were higher in the serum (6.58 +/- 0.98 [mean +/- standard deviation]) and CSF (4.38 +/- 0.74) of SSPE patients compared with controls. Anti-M antibodies were present in the serum and CSF of all SSPE samples tested but in titers lower than those of anti-NC antibodies. Geometric mean anti-M antibody titer was 3.35 +/- 0.53 in sera from patients with SSPE compared with 3.05 +/- 0.66 in sera from patients with other neurological diseases and 3.12 +/- 0.74 in sera from healthy individuals. Geometric mean anti-M antibody titer was 2.59 +/- 0.86 in the CSF of eight patients with SSPE compared with a mean less than 1.00 for patients with other neurological disease (controls). Intrathecal synthesis of anti-M or anti-NC antibodies was established in four patients with SSPE. The cellular immune responses to M, F, HA, and NC proteins were examined in four of the patients with SSPE by lymphoproliferation and were not significantly different from those in five healthy controls. The results demonstrate humoral and cellular immune responses to M protein in patients with SSPE and indicate that it is unlikely that a defect in the immune response to this virus component accounts for the disease process in the patients studied.  相似文献   

2.
Studies in 13 normal subjects, 9 patients with multiple sclerosis (MS) within 3 weeks of exacerbation and 16 others 1 to 6 months after onset were carried out for evidence of cell-mediated hypersensitivity to myelin basic protein. Ten patients with stroke and 10 with Guillain-Barré syndrome were studied as additional controls. Peripheral leukocytes obtained by leukapheresis were packed into capillary tubes and allowed to migrate out onto glass in the presence or absence of myelin basic protein. Cells of patients within 3 weeks of an MS episode gave a mean migration index of 68 +/- 9%, and those 1 to 6 months after onset, 93 +/- 21%. For the entire MS group the mean index was 88 +/- 20%, for those with Guillain-Barré, 103 +/- 7%; and for the stroke patients, 107 +/- 11%. Results for the acutely ill MS patients were significant (P less than 0.005). The data are similar to those obtained using the migration inhibition factor assay but show that sensitized lymphocytes also elaborate a second mediator during acute exacerbations of illness. These observations strengthen evidence that sensitization to this potent encephalitogen occurs simultaneously with exacerbations of clinical illness.  相似文献   

3.
Myelin was isolated from normal-appearing white matter from the brains of 11 multiple sclerosis (MS) patients, 11 normal individuals, and 1 patient with subacute sclerosing panencephalitis (SSPE). Ratios of protein, cholesterol, and phospholipid content, total fatty acid content, and total amino acid content were determined. The lipid bilayer fluidity of the myelin was measured using electron spin resonance and fluorescence polarization spectroscopy. The protein-to-phospholipid ratio was higher than normal, the cholesterol-to-protein ratio was lower than normal while the cholesterol-to-phospholipid ratio was normal in MS myelin. This suggested a relative increase of protein to lipid content in MS myelin. Of the fatty acid content of a total lipid extract, MS myelin had relatively more 16:0, less 18:3, and less 22:3, 24:1 than normal. The total amino acid content of MS myelin was altered in a way which suggested a decreased percentage of basic protein and an increased percentage of proteolipids. SSPE myelin had similar changes in amino acid content but not in protein-to-cholesterol or-phospholipid ratios or fatty acid content as MS myelin. There was no significant difference in myelin fluidity, however, between MS and normal myelin using fatty acid spin labels or fluorescent probes. A correlation was found between the fluidity and the cholesterol-to-phospholipid ratio but the MS and normal samples varied over a similar range. Although these alterations in lipid and protein composition had no effect on fluidity, they may nevertheless have serious consequences for myelin structure.  相似文献   

4.
In 1982 a two dose regimen was introduced in Sweden for the combined vaccination against measles, mumps, and rubella of children aged 18 months and 12 years. Since 1977 about half of the preschool children were vaccinated against measles annually, and since 1974 about 80% of 12 year old girls were vaccinated against rubella. During the period 1982 to 1985 90-93% of the eligible age cohorts of 18 month old children and 88-91% of the 12 year old children were immunised with the new combined vaccine. A study in 1982 of about 140 18 month old children who were nearly all seronegative before vaccination showed that 96%, 92%, and 99% seroconverted against measles, mumps, and rubella, respectively. A second study was carried out in 1983 of 247 12 year old children, of whom 11% lacked antibodies to measles, 27% to mumps, and 45% to rubella. This showed seroconversion in 82% and 80% against measles and mumps, respectively, and all children seroconverted against rubella. In the latest study in 1985 of 496 12 year olds 9% and 13% were seronegative against measles and mumps before vaccination, and 41% against rubella. Of these, 88% seroconverted to measles and 80% to mumps, and all converted to rubella when sera were tested by the haemolysis in gel method. After a neutralisation test against measles as well all children showed immunity to the disease. A low incidence of measles and declining figures for mumps and rubella were reported in 1984 to 1986. An outbreak of rubella during 1985 affected mainly boys in age cohorts in which only the girls had been vaccinated during the 1970s.  相似文献   

5.
Four murine anti-idiotypic (a-Id) hybridoma antibodies were produced against immunoglobulins (Ig) present in the cerebrospinal fluid (CSF) obtained from an MS patient 2 mo after the onset of disease. The four a-Id antibodies were shown to delineate idiotopes present on three distinct Ig subpopulations designated ID-19, ID-40, and ID-97. All three Ig subpopulations were produced in part by intrathecally localized B cells, together making up approximately 5% of the total CSF-Ig 2 mo after the onset of disease. Longitudinal analysis of the concentration of these Ig subpopulations in CSF showed that two subpopulations, ID-40 and ID-97, exhibited a regular relation to the clinical course of the disease, i.e., were decreased (ID-40) or increased (ID-97) in the first CSF sample obtained after two consecutive exacerbations. Screening of sera from 52 optic neuritis patients and 51 heterologous MS patients revealed that one MS patient's serum contained an Ig subpopulation that was idiotypically cross-reactive with ID-97. So far, screening of these Ig subpopulations for reaction with several viruses (measles, parainfluenza type 1, influenza type A, cytomegalovirus, herpes simplex virus, rubella virus, poliovirus, murine encephalomyelitis viruses, and reovirus) and myelin basic protein has failed to reveal their antigen specificities.  相似文献   

6.
Measles virus protein synthesis has been analyzed in acutely and persistently infected cells. To assess the role of measles in subacute sclerosing panencephalitis (SSPE), measles viral proteins synthesized in vivo or in vitro were tested for reactivity with serum from a guinea pig(s) immunized with measles virus and sera from patients with SSPE. Guinea pig antimeasles virus serum immunoprecipitates the viral polypeptides of 78,000 molecular weight (glycosylated [G]), 70,000 molecular weight (phosphorylated [P]), 60,000 molecular weight (nucleocapsid [N]), and 35,000 molecular weight (matrix [M]) from cells acutely infected with measles virus as well as from chronically infected cells, but in the latter case, immunoprecipitated M protein has a reduced electrophoretic migration. Sera of SSPE patients immunoprecipitated all but the G protein in acutely infected cells and only the P and N proteins from chronically infected cells. In immunoprecipitates of viral polypeptides synthesized in a reticulocyte cell-free translation system, in response to mRNA from acutely or persistently infected cells, the 78,000-molecular-weight form of the G protein was not detected among the cell-free products of either mRNA. Guinea pig antimeasles virus serum immunoprecipitated P, N, and M polypeptides from the products of either form of mRNA, whereas SSPE serum immunoprecipitated the P and N polypeptides but not the M polypeptide. The differences in immunoreactivity of the antimeasles virus antiserum and the SSPE serum are discussed in terms of possible modifications of measles virus proteins in SSPE.  相似文献   

7.
Comparative evaluation of avidity of IgG to rubella virus in vaccinated persons, in patients with rubella or other exanthematous illness, and in healthy persons revealed similar patterns in post-vaccination and post-infection immunity. Virus specific low avidity IgG (index of avidity < or =30%) were detected in patients with rubella during 7 weeks after symptoms appeared as well as in vaccinated persons which were tested 6 weeks after vaccination. Low avidity antibodies in sera were detected in 96% of patients with rubella and in 75% of vaccinated persons which were not immune before immunization. Live attenuated vaccines Ervevax, Priorix, and MMR-II had similar ability to induce low avidity IgG to rubella virus. Increase of low avidity antibodies concentration was noted after immunization of children with low levels of antibodies before vaccination. After immunization of persons with high avidity antibodies in serum, index of avidity remained above threshold. Anamnestic high avidity IgG (index of avidity 51-100%) were detected in majority of immune healthy persons (96.4%) as well as in patients with exanthematous illnesses not related to rubella infection (93.6%). ELISA test-systems for detection of low avidity IgG to rubella virus allow to obtain reliable information about seroconversion rate and characteristics of immune response in vaccines. Detection of low avidity IgG in serum obtained 5-6 weeks after immunization points to primary immune response, whereas identification of high avidity antibodies reveals already immune persons.  相似文献   

8.
Autoimmunity to the central nervous system (CNS), especially to myelin basic protein (MBP), may play a causal role in autism, a neurodevelopmental disorder. Because many autistic children harbor elevated levels of measles antibodies, we conducted a serological study of measles-mumps-rubella (MMR) and MBP autoantibodies. Using serum samples of 125 autistic children and 92 control children, antibodies were assayed by ELISA or immunoblotting methods. ELISA analysis showed a significant increase in the level of MMR antibodies in autistic children. Immunoblotting analysis revealed the presence of an unusual MMR antibody in 75 of 125 (60%) autistic sera but not in control sera. This antibody specifically detected a protein of 73-75 kD of MMR. This protein band, as analyzed with monoclonal antibodies, was immunopositive for measles hemagglutinin (HA) protein but not for measles nucleoprotein and rubella or mumps viral proteins. Thus the MMR antibody in autistic sera detected measles HA protein, which is unique to the measles subunit of the vaccine. Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. Stemming from this evidence, we suggest that an inappropriate antibody response to MMR, specifically the measles component thereof, might be related to pathogenesis of autism.  相似文献   

9.
Immune precipitation was used to study the humoral immune response of patients with subacute sclerosing panencephalitis (SSPE). Patients with SSPE have a progressive infection of the CNS by measles or a measles variant despite high serum antibody levels to measles virus as measured by standard serologic techniques. However, when the antibody response to individual measles virus proteins was measured, we found a striking reduction in the ability of sera from patients with SSPE to precipitate the matrix (M) protein as compared to the precipitation of the M protein by sera from normal adults who had natural measles infection in childhood, or by convalescent sera obtained 3 to 5 weeks after a naturally occurring measles infection. The decreased antibody response to the M protein in sera from patients with SSPE occurred despite a vigorous antibody response to the other viral proteins, suggesting a selective defect in the production of antibody to a single viral protein. The reduced anti-M antibody in sera from patients with SSPE was demonstrated whether immune precipitation was performed with wild-type measles virus or SSPE virus proteins. These results suggest that in SSPE only small amounts of the M protein are produced. This result may help explain how measles virus persists in the central nervous system of patients with SSPE.  相似文献   

10.
Young adult male ferrets were inoculated intracerebrally (i.c.) with a cell-associated encephalitogenic subacute sclerosing panencephalitis (SSPE) virus strain to study the pathogenesis of the disease at the ultrastructural level. Most became acutely ill in 8-13 days. Areas of the brain were examined with indirect immunoperoxidase labeling techniques to detect measles antigen. None of these animals showed the characteristic viral nucleocapsids or marked inflammatory response associated with SSPE. However, all had positive immunolabeling of unstructured virus antigen, especially in post-synaptic regions in all areas of the brain that were examined. One ferret, immunized with measles vaccine 40 days prior to challenge with SSPE, became ill 18 days post inoculation (p.i.). Perivascular cuffings of inflammatory cells and large cytoplasmic inclusions of fuzzy nucleocapsids were found in the brain and spinal cord. The study indicates that ferrets which become acutely ill after inoculation with cell-associated SSPE virus do so before there is a marked cellular immune response or formation of virus nucleocapsids.  相似文献   

11.
A highly sensitive procedure of solid-phase radioimmunoassay (RIA) was developed for the detection of measles IgG antibody. HeLa cells persistently infected with measles virus were used as a solid-phase antigen. This technique was applied to the detection of measles IgG antibody in patients with subacute sclerosing panencephalitis (SSPE) and multiple sclerosis. Normal subjects having experienced natural measles or measles vaccination and patients with various neurological diseases of non-virus nature were also examined as control groups. Measles antibody was detected at high titers in both the sera and cerebrospinal fluid of SSPE patients. Moreover, RIA/HI ratios of SSPE patients were significantly higher than those of normal subjects, suggesting the presence in the formers of antibodies to nucleocapsids at high titers as well as to viral envelopes. On the other hand, no significant difference was found in both RIA and HI titers between the sera of multiple sclerosis and those of various neurological diseases.  相似文献   

12.
Sero-epidemiological studies on a few common virus infections, including measles, rubella, mumps and varicella-zoster, were carried out on patients with multiple sclerosis (MS) and controls matched for age, sex, and residences since birth. The frequency of antibodies against measles was significantly higher in the MS patients. Where measles preceded the onset of MS, the time interval varied from 3 to 32 years. In two cases, known MS patients contracted measles 9 and 3 years after their onset of MS. Furthermore, three MS patients were vaccinated against measles as adults. Two of these took part in a WHO measles vaccine trial in 1962, 18 and 6 years after the onset of MS. Both of them were seronegative prior to vaccination.  相似文献   

13.
We have undertaken a seroprevalence study with more than 13,000 children, who had been included in the German KIGGS survey, a representative sample of children and adolescents 0-17 years of age. The IgG titres against measles, mumps and rubella were determined in 1 to 17 year olds While 88.8% of the children were MMR-vaccinated at least once, 76.8% of children aged 1 to 17 years showed prevalence of antibodies to MMR. The highest seronegativity was seen with respect to mumps. Gender differences were most pronounced with regard to rubella IgG titres: girls aged 14 to 17 years were best protected, although seronegativity in 6.8% of this vulnerable group still shows the need of improvement. Search for predictors of missing seroprevalence identified young age to be the most important predictor. Children living in the former West and children born outside of Germany had a higher risk of lacking protection against measles and rubella, while children with a migration background but born in Germany were less often seronegative to measles antibodies than their German contemporaries. An association of seronegativity and early vaccination was seen for measles but not for mumps and rubella. A high maternal educational level was associated with seronegativity to measles and rubella. In vaccinated children, seronegativity was highest for mumps and lowest for rubella. For mumps, high differences were observed for seronegativity after one-dose and two-dose vaccination, respectively. Seronegativity increases as time since last vaccination passes thus indicating significant waning effects for all three components of MMR.  相似文献   

14.
A trivalent measles-mumps-rubella live virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was evaluated in 229 children, aged 1 to 5 years. The vaccine induced a high seroconversion rate: 221 (98.7%) out of 224 subjects initially seronegative for measles virus, 167 (93.3%) out of 179 initially seronegative for mumps virus, and 212 (99.1%) out of 214 initially seronegative for rubella virus. It also induced a sufficient cellular immunity against each of the three viruses in over 90% of the subjects, as judged by virus-specific interferon-gamma (IFN-gamma) production. Virus-specific IFN-gamma production was observed 10 days after vaccination by stimulation with measles virus and rubella virus and 14 days after vaccination by stimulation with mumps virus. Mumps-virus-specific IFN-gamma production was observed in 7 out of 12 recipients without seroconversion for mumps virus. And measles-virus-specific IFN-gamma production was demonstrated in one out of three recipients without seroconversion for measles virus. A significant correlation was observed between the serum antibody and IFN-gamma production six weeks after vaccination for measles virus (r = 0.201, P less than 0.01) and for mumps virus (r = 0.174, P less than 0.05) but not for rubella virus (r = -0.045, P less than 0.05). The incidence of febrile reactions of greater than or equal to 37.5 C was quite low, 14.4%, and that of greater than or equal to 39 C occurred in only 1.3% of the recipients. These results suggested that the trivalent vaccine induced sufficient humoral and cellular immunity and yet resulted in no more untoward reaction than observed from the measles vaccine alone.  相似文献   

15.
Consistent results have not been obtained yet on the presence of antibody to the M protein of measles virus in the sera of patients with subacute sclerosing panencephalitis (SSPE). We performed a comparative study on various immunoprecipitation systems which appeared in the literature and found that the difference in the composition of the solubilizing buffer produced a large variety of results on the immunoprecipitation. [35S]Methionine-labeled Vero cells infected with the Edmonston strain of measles virus were solubilized by 10 different buffers and reacted with hyperimmune rabbit serum to whole virus, monospecific antisera to H, NP, and M proteins of the virus, normal adults' sera, and the sera from 16 SSPE patients. The immune complex was absorbed by protein A and both solubilization and precipitation rates were compared with each viral protein. Although viral proteins were solubilized by all buffers, the solubilization rate varied considerably. M protein was solubilized and was not coprecipitated nonspecifically with any of the other viral proteins. Purified protein A conjugated to Sepharose was preferable to Staphylococcus aureus for absorption of the immune complex since the latter absorbed both viral and host proteins nonspecifically. The precipitation rates of the viral proteins also varied according to the buffers. Better solubilization of the viral proteins seemed to reduce their rate of precipitation for which the presence of SDS may be responsible, and the presence of the protease inhibitors may also affect the results of immunoprecipitation. Detection of M protein in the immunoprecipitates was largely influenced by the kind of buffer used: some buffers could detect it clearly, but others could not defect it at all. Among the solubilizing buffers tested, Saleh's buffer (Virology 93: 369-376 (1979)),, which contains 0.5% DOC and 0.5% Triton X-100, was most reliable for detection of the anti-M antibody in the rabbit serum, because it showed a high solubilization and high precipitation rates of viral proteins without nonspecific absorption by protein A or coprecipitation of M proteins with any of the other proteins. Using this buffer, we could definitely detect M proteins in the immunoprecipitates from the sera of all six healthy adults and 15 out of 16 patients with SSPE. It was found, however, that the amount of M proteins in SSPE patients was lower than that in healthy adults and varied considerably.  相似文献   

16.
目的了解潍坊市健康人群麻疹、风疹、流行性腮腺炎血清抗体水平,为消除麻疹、控制风疹及腮腺炎疫情提供依据。方法 2011年8月,采集昌乐、潍城2个县区<2、2~5、5~8、8~11、11~15、15~20、20~40、>40岁健康人群血标本,应用酶联免疫吸附试验检测麻疹、风疹、腮腺炎IgG抗体。结果检测总数320人,其中昌乐县健康人群的麻疹抗体阳性率为98.75%、潍城为96.25%;风疹抗体阳性率昌乐县健康人群为89.38%、潍城区为91.88%。昌乐、潍城两地区健康人群麻疹、风疹的抗体阳性率差异均无统计学意义(χ2=1.15、0.59,P>0.05);昌乐县健康人群腮腺炎抗体阳性率为84.38%、潍城区健康人群为66.25%,两者差异有统计学意义(χ2=14.14,P<0.01);8组不同年龄健康人群的麻疹抗体阳性率为92.50%~100%,风疹抗体阳性率为87.50%~92.50%,腮腺炎抗体阳性率为67.50%~85.00%,各年龄组间均无统计学意义(χ2=13.49、1.58、5.23,P>0.05)。结论潍坊市麻疹抗体阳性率较高,风疹、腮腺炎抗体阳性率相对偏低,今后须要积极开展学龄儿童麻腮风三联疫苗的查漏补种工作。  相似文献   

17.
The etiology of multiple sclerosis (MS) remains unclear. To determine if autoantibodies to myelin basic protein (MBP) are produced during parvovirus B19 infection, a competitive ELISA was performed using plasma from MS patients exhibiting high IgG titers for parvovirus. Our results showed the addition of MBP decreased the binding of IgG to B19 antigen in a dose dependent fashion suggesting a possible link between parvovirus B19 and a subset of patients with clinical MS.  相似文献   

18.
Borrelial encephalomyelitis, a rare manifestation of Lyme borreliosis, may present as a multiple sclerosis (MS)-like disease. It is postulated that in MS, inflammation of the white matter is caused by a T-cell response directed to myelin antigens. Here, we examined whether a T-cell autoimmune response may play a pathogenetic role in Borrelia-associated white matter disease mediated by cross-reactivity between myelin basic protein (MBP) and B. burgdorferi. We generated a total of 1760 short-term T-cell lines against B. burgdorferi or MBP from two patients with Borrelial encephalomyelitis and compared these with three patients with late Lyme disease, one patient with transverse myelitis, eight patients with MS, and four healthy controls. While a few T-cell lines recognized both B. burgdorferi and MBP, T-cell clones from these lines responded only to the antigen of the original stimulation. Thus, our data do not provide evidence for cross-reactivity between MBP and B. burgdorferi.  相似文献   

19.
We have previously shown that patients with multiple sclerosis (MS) have increased T cell responses to the immunodominant region (residues 184-209) of myelin proteolipid protein (PLP). The present study investigated whether this reactivity fluctuates over time and correlates with disease activity. We performed monthly limiting dilution assays for 12-16 mo in four healthy subjects and five patients with relapsing-remitting MS to quantify the frequencies of circulating T cells proliferating in response to PLP(41-58), PLP(184-199), PLP(190-209), myelin basic protein (MBP), MBP(82-100), and tetanus toxoid. Disease activity was monitored by clinical assessment and gadolinium-enhanced magnetic resonance imaging of the brain. There were fluctuations in the frequencies of autoreactive T cells in all subjects. Compared with healthy controls, MS patients had significantly more frequent surges of T cells reactive to the 184-209 region of PLP, but infrequent surges of T cell reactivity to MBP(82-100). There was temporal clustering of the surges of T cell reactivity to MBP(82-100) and MBP, suggesting T cell activation by environmental stimuli. Some clinical relapses were preceded by surges of T cell reactivity to PLP(184-209), and in one patient there was significant correlation between the frequency of T cells reactive to PLP(184-199) and the total number of gadolinium-enhancing magnetic resonance imaging lesions. However, other relapses were not associated with surges of T cell reactivity to the Ags tested. T cells reactive to PLP(184-209) may contribute to the development of some of the CNS lesions in MS.  相似文献   

20.
Differences have been observed between myelin vesicles prepared from normal human central nervous system and from white matter of patients who died with multiple sclerosis (MS). The mean cross-sectional area of the vesicles was 5.69 +/- 0.17 micron 2 from normal myelin and 3.71 +/- 0.28 micron 2 for diseased myelin. Vesicle size was reduced to 4.08 +/- 0.21 micron 2 when normal myelin vesicles were prepared in the presence of 0.1 mM EDTA. The presence of Ca2+ during the preparation of the vesicles had no effect on the mean cross-sectional area. In the case of MS myelin vesicles, 0.1 mM EDTA had no effect on vesicle size, whereas the presence of Ca2+ increased the vesicle size from 3.71 +/- 0.28 to 5.40 +/- 0.31 micron 2. Electrokinetic analysis revealed that the electrophoretic mobility of normal myelin vesicles was -5.169 +/- 0.193 X 10(-8) compared with -6.093 +/- 0.202 X 10(-8) m2 s-1 V-1 for the MS myelin vesicles. The presence of 0.1 mM EDTA increased the electrophoretic mobility of the normal vesicles to -6.483 +/- 0.151 X 10(-8) m2 s-1 V-1 but did not significantly affect that of the MS vesicles. Addition of 0.1 mM Ca2+ decreased the electrophoretic mobility of both normal and MS vesicles to similar mobilities. From these data, the surface charge densities were calculated for both normal and MS myelin vesicles and found to be -2.93 and -5.39 mV m-1, respectively. The phase transition temperature determined by wide-angle x-ray diffraction studies was 63 degrees C for normal myelin vesicles and 43 degrees C for MS myelin vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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