Serum levels of matrix metalloproteinase-2, -9, and vitamin D in patients with multiple sclerosis with or without herpesvirus-6 seropositivity

ABSTRACT In recent years, extreme attention has been focused on the role of human herpesvirus-6 (HHV-6) in multiple sclerosis (MS) pathogenesis. However, the pathogenesis of MS associated with HHV-6 infection remains unknown. In this study, we measured the serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection. Five hundred sixty (including 300 females and 260 males) MS patients along with 560 healthy subjects were analyzed for HHV-6 seropositivity using enzyme-linked immunosorbent assay (ELISA). Subsequently, we measured the serum levels of MMP-2, MMP-9, and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection by ELISA. About 90.7% of MS patients (508/560) were seropositive for HHV-6, while 82.3% (461/560) of healthy subjects were seropositive for this virus (p = 0.001). Moreover, there was a significant increase in the levels of MMP-2, MMP-9, and lower vitamin D in the serum samples of MS patients when compared with healthy subjects. Additionally, we demonstrated that the MMP-9 levels in seropositive MS patients were significantly higher than seronegative MS patients (p = 0.001). Finally, our results demonstrated that the mean of expanded disability status scale (EDSS) in seropositive MS patients was significantly higher in comparison to seronegative MS patients (p < 0.05). In conclusion, we suggest that the HHV-6 infection may play a role in MS pathogenesis.

[Anti-human herpes virus-6 antibodies titer in patients with multiple sclerosis in Markazy Province]

Multiple sclerosis [MS] is a auto-immune disease of central nervous system. The etiology of MS is unknown, but environmental factors such as viruses are involved in the development of MS. In this study, MS patients were assessed for antibodies titers against Human Herpes virus-6 [HHV-6] in Markazi Province. In this case-control study, 31 new cases of MS patients and 60 healthy subjects were selected with similar demographic criteria such as sex, age and location. Antibodies titer [IgM and IgG] against HHV-6 were examined by ELISA and Immunofluorescence methods. Data were analyzed using Logistic regression and Odds ratio. Data indicates that 74.2% of case group and 34.2% of control group were identified as positive for IgM against HHV-6. The difference between the two groups in terms of IgM against HHv-6 was statistically significant [p=0.001]. Incidence of IgM positivity against HHV-6 was increased more than five times in MS patients compared to control group. Also there was a statistically significant difference between case and control groups in IgG titer [p=0.019]. Acute infection of HHV-6 is a risk factor for MS

Human herpes virus 6 antibodies in beta-thalassemia/hemoglobin E pediatric patients.

Human herpesvirus 6 (HHV-6) is a viral pathogen that causes exanthem subitum in children. It has also been identified as the cause of life-threatening illness in immunocompromised pediatric patients and transplant recipients. We undertook a serological study of HHV-6 IgM and IgG antibody among 29 children (12 females and 17 males) with beta-thalassemia/HbE disease. The rate of infection was 86.2%; the rates of early recent infection (IgM positive only), recent infection (both IgM and IgG positive) and past infection (IgG positive only) were 13.8%, 41.4% and 31.0%, respectively. The geometric means of the IgM and IgG titers of the splenectomy group (9 cases) were 10.15 units and 11.18 units, respectively. The geometric means of the IgM and IgG titers of the non-splenectomy group (20 cases) were 10.10 units and 12.84 units, respectively. According to this study, the prevalence of HHV6 infection among pediatric patients with beta-thalassemia/HbE is very high; morever, the significantly higher titer among these patients may imply a high risk for further possible bone marrow transplantation. Increased awareness of HHV-6 infection among this population is necessary.

Seroprevalence of anti-human herpes virus-6 IgG antibody in children of Bangkok, Thailand.

The prevalence of HHV-6 infection was surveyed by determining the presence of anti-human herpesvirus-6 IgG (Anti-HHV-6 IgG) using an ELISA method. Two hundred and ten sera collected from healthy Thai children aged between 0 to 12 years (mean +/- standard deviation = 3.35+/-3.33) indicated the prevalence of HHV-6 infection was 88.10% (185/210). Samples were classified into 7 groups, 30 samples each, according to their ages, ie, group 1: 0 - < 6 months; group 2: 6 - < 12 months; group 3: 12 - < 18 months; group 4; 18 - < 24 months; group 5: 2 - < 5 years; group 6: 5 - < 8 years and group 7: 8-12 years. The prevalence of HHV-6 infection was 63.33%, 70%, 96.67%, 93.33%, 100%, 100% and 93.33%, respectively. The mean level of anti-HHV-6 IgG among those positive for HHV-6 infection (185 samples) increased from 0 < 6 months old (17.47+/-6.32 units) to 27.57+/-8.42 units in 6 - < 12 months old, with the highest value found in the 18 - < 24 months old group (33.08+/-8.64 units). The level declined thereafter. A statistically significant difference of the mean level of anti-HHV-6 IgG among positive groups was found (p-value < 0.05). The important factor associated with HHV-6 infection was age (p = 0.002), while sex, socioeconomic status, number of children in the family and child rearing place did not show any association.

Outbreaks of human-herpes virus 6 (HHV-6) infection in day-care centers in Belém, Pará, Brazil

A total of 730 children aged less than 7 years, attending 8 day-care centers (DCCs) in Belém, Brazil were followed-up from January to December 1997 to investigate the occurrence of human-herpes virus 6 (HHV-6) infection in these institutional settings. Between October and December 1997 there have been outbreaks of a febrile- and -exanthematous disease, affecting at least 15-20 percent of children in each of the DCCs. Both serum- and- plasma samples were obtained from 401 (55 percent) of the 730 participating children for the detection of HHV-6 antibodies by enzyme-linked immunosorbent assay (ELISA), and viral DNA amplification through the nested-PCR. Recent HHV-6 infection was diagnosed in 63.8 percent (256/401) of them, as defined by the presence of both IgM and IgG-specific antibodies (IgM+/IgG+); of these, 114 (44.5 percent) were symptomatic and 142 (55.5 percent) had no symptoms (p = 0.03). A subgroup of 123 (30.7 percent) children were found to be IgM-/IgG+, whereas the remaining 22 (5.5 percent) children had neither IgM nor IgG HHV-6- antibodies (IgM-/IgG-). Of the 118 children reacting strongly IgM-positive ( > or = 30 PANBIO units), 26 (22.0 percent) were found to harbour the HHV-6 DNA, as demonstrated by nested-PCR. Taken the ELISA-IgM- and- nested PCR-positive results together, HHV-6 infection was shown to have occurred in 5 of the 8 DCCs under follow-up. Serological evidence of recent infections by Epstein-Barr virus (EBV) and parvovirus B19 were identified in 2.0 percent (8/401) and 1.5 percent (6/401) of the children, respectively. Our data provide strong evidence that HHV-6 is a common cause of outbreaks of febrile/exanthematous diseases among children attending DCCs in the Belém area

Apresentacao clinica de 52 criancas com exantema causado pelo Herpesvirus Humano tipo 6 / Clinical profile of 52 children with exhantem caused by human herpvirus type 6

Os autores descrevem e analisam manifestacoes clinicas observadas em criancas com exantema causado pelo Herpesvirus tipo 6. Foi realizado estudo prospectivo no Servico de Pronto-Atendimento Pediatrico do Hospital Universitario da USP, durante 15 meses, com as criancas que apresentavam exantema generalizado nao-bolhoso. Os pacientes deste grupo inicial foram examinados e receberam um diagnostico clinico previo. Destas criancas, foram incluidas na casuistica do presente estudo apenas as criancas menores de tres anos, que tivessem comprovacao laboratorial da presenca do Herpesvirus tipo 6 no sangue. O estudo laboratorial foi realizado atraves da reacao de polimerizacao em cadeia do acido nucleico do Herpesvirus humano tipo 6, em linfocitos de sangue periferico...

Apoptosis y proliferación celular en infecciones por el virus Herpes humano 6 (HHV-6). Mecanismos de regulación a través de interacciones de p53, bcl-2, ras y p21WAF / Apoptosis and celular proliferation in human herpes virus 6 (HHV-6) infection. Mechanism as of regulation by interactions of p53, bcl2, ras and p21WAF

Se analizaron inmunohistológicamente líneas de cultivo celular infectadas con el HHV-6: HSB2-células T inmaduras y HDLM2-células de Hodgkin, así como ganglios linfáticos de pacientes con enfermedad de Hodgkin y linfadenitis de Kikuchi-Fujimoto (LKF) en relación a la expresión de los productos oncógenos/antioncógenos p53, bcl-2, ras y p21WAF. Se comprobó la proliferación celular inmunohistológicamente mediante anticuerpos contra PCNa (antígeno nuclear de proliferación celular) y la apoptosis se investigó en cortes finos de tejido ganglionar, analizando el ADN fragmentado con marcación final in situ. La LKF mostró alta incidencia de focos de células muertas (linfadenitis histiocítica necrozante), mientras que en la enfermedad de Hodgkin se observó proliferación celular. Con las técnicas utilizadas no se logró mostrar diferencias significativas en la expresión de ADN viral no de antígenos en las líneas celulares, ni en las biopsias de enfermedad de Hodgkin y de LKF. Las células HDLM2 con mejor viabilidad posterior a la infección con HHV-6 y un grado de apoptosis inferior, mostraron una expresión de p53 y de PCNA mucho menor que las células HSB2. Las biopsias de LKF no expresaron p53; ras se observó en menores células que en la enfermedad de Hodgkin y la positividad de PCNA fue tres veces mayor en enfermedad de Hodgkin en comparación con LKf. Sin embargo el bcl-2 se observó con mayor frecuencia en LKF que en enfermedad de Hodgkin. Los resultados no son de fácil interpretación; los datos sugieren la implicación de otros factores exógenos (por ejemplo, citoquinas y factores de crecimiento) en el mecanismo regulatorio de la proliferación celular y de la apoptosis, ambas inducidas probablemente por virus

Seroepidemiology of human herpesvirus 6 in a population seen in the University Hospital, Kuala Lumpur, Malaysia.

Sera from healthy donors and patients stored over a period of 2 years, aged 1 to 83 years, were examined for reactivity to human herpes virus 6 (HHV-6) by the standard indirect immunofluorescence assay (IFA). Of the 600 serum specimens screened, 502 showed positive reactivity to HHV-6. This gives an overall seropositive rate of 83.7%. There is no significant difference in the overall positive rate between the ethnic groups (Chinese, Malays, Indians) (chi 2 = 0.35 df = 2 p > 0.05). However, there is significant difference in the positive rates at the extreme age groups of 1 year as well as 61 years and above. From birth up to below 1 year of age, the seroprevalence rate was 82%. At one year of age the positive rate decreased to 66% before gradually rising so that the percentage seropositivity of 6 to 10 years old becomes similar to that in older children and adults (11 to 40 years). The positive rate then starts to decline after 40 years of age. Using a standardized scoring system, the corresponding antibody titer was found to be high in the very young population and starts to decline after the age of 15 years. This suggests that in our population group, primary infection occurs mainly in the pediatric age group. It also accounts for the low positive rate in the age group of 61 years and above, as by then the titer had fallen to the level below the detection limits of the assay system.

Seroprevalence of human herpesvirus 6 and 7 infections in the Thai population.

Seroprevalence of human herpesvirus 6 (HHV-6) and 7 (HHV-7) was estimated in the Thai population using indirect immunofluorescence assay to determine serum antibodies to HHV-6 and HHV-7. A total of 333 serum samples obtained from umbilical cord blood and venous blood of healthy persons at Siriraj Hospital and Krabi Hospital during 1990-1993 were investigated. Of 73 infants aged 0-1 month, 73% and 78% were found tob e positive for HHV-6 and HHV-7 antibodies, respectively. Antibody to HHV-6 was detected in age groups 2-3 months (38%), 4-5 months (14%), 6 months (44%), 7-11 months (66%), 1-2 year (84%), 3-4 years (82%), 5-9 years (83%), 10-19 years (83%), 20-29 years (80%), 30-39 years (67%), and over 40 years (58%), respectively. This positive rates of HHV-7 antibody in age groups 2-3 months, 4-5 months, 6 months, 7-11 months, 1-2 years, 3-4 years, 5-9 years, 10-19 years, 21-29 years, 30-39 years, and over 40 years were 50%, 21%, 10%, 37%, 47%, 82%, 75%, 72%, 72%, 67%, and 67%, respectively. At 6 months of age as the starting time of infections, 34% (14/41) and 9% (3/41) of infants had presumed primary infections of HHV-6 and HHV-7, respectively. In the follow-up study, 53% (20/38) of children were infected with HHV-6 prior to HHV-7 and only 5% vice versa. Eighty-four percent of children had acquired antibody to HHV-6 by 1-2 years old while 82% of children had acquired antibody to HHV-7 by 3-4 years old. These results suggest that HHV-6 and HHV-7 are prevalent viruses in the Thai population. The infections of both viruses begin at 6 months of age. However, infection of HHV-7 in most children begins later. The data also provided evidence that antigenic distinction between HHV-6 and HHV-7 existed with a limited cross-reactivity in an antibody test. The antibody responses to HHV-6 and HHV-7 occurred independently.

Cytomegalovirus, human herpesvirus 6 and human T cell leukemia virus infection in renal transplanted patients in the northeast of Brazil

The seroprevalence of antibodies against cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and human T cell leukemia virus type 1 (HTLV-1), determined by ELISA and by fluorescence in 54 renal transplanted patients, was 96.2 per cent , 88.8 per cent and 11.1 per cent , respectively. These values are relatively high when compared with the results obtained for healthy individuals of the same age groups from Recife, Northeastern Brazil. Active CMV infection was detected by the presence of IgM antibodies and/or virus isolation in 13 (24 per cent ) patients. Kidney rejection and renal dysfunction were observed in 11 of these 13 patients, whereas 3 of 6 HTLV-1 antibody-positive individuals presented these complications. All HTLV-1 positive patients were also positive to IgG CMV and HHV-6 antibodies. The importance of the three viruses in this clinical condition is suggested by the high seropositivity rates compared with the healthy population. The group may also represent a potential source of HTLV-1 infection in this non-endemic area