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Tove Christensen

Publications and source records attributed to Tove Christensen.

6 recordsLinked to original sources
PubMed2006

Gene-environment interactions in multiple sclerosis: innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway.

Aspects of gene-environment interactions in multiple sclerosis (MS) were analysed in serum samples from 46 MS families (25 sporadic MS cases and 42 familial MS cases): antibodies to the MS-associated human endogenous retrovirus HERV-H, and levels of three components in the innate pathogen-associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-2 and MASP-3. For representative MS families, we also determined herpesvirus serology for HSV-1, VZV, and EBV; and tissue typed for HLA-B, and HLA DR and DQ. In MS, a significant correlation between elevated immune reactivity to HERV-H Env and disease activity was demonstrated, as were indications of a protective effect of high MBL and MASP-3 levels. The HLA alleles B*07, DRB*02, and DQB1*06 were commonly present together in the MS families, both in MS patients, and in unaffected family members. Our results support that HERV-H and the antiviral immune response may play a role in MS development, and also underline the tenuous nature of specific genetic contributions to this complex disease.

Adult↗
PubMed2004

Simultaneous presence of endogenous retrovirus and herpes virus antigens has profound effect on cell-mediated immune responses: implications for multiple sclerosis.

Retroviruses have been suggested as possible pathogenic factors in multiple sclerosis (MS), supported by the observation that endogenous retroviruses are activated in MS patients. Different members of the herpes family of which several are neurotropic have also been suggested as factors in MS pathogenesis. Further, interactions between retroviruses and herpes viruses have been implied in the development of MS. The objective of the study was investigation of cell-mediated immune responses of MS patients to retrovirus and herpes virus antigens, particularly antigen combinations, with analyses of the influence of retrovirus antigens on cellular immunological reactivity toward other viral antigens. Cellular immunity as measured by blast transformation assays was analyzed using freshly isolated peripheral blood mononuclear cells from 47 MS patients and 36 healthy volunteers. Combinations of the endogenous retrovirus HERV-H and herpes virus antigens resulted in highly increased cellular immune responses among both the MS patients and healthy subjects. The increase was synergistic in character in most samples. Very pronounced effects were obtained using HHV-6A and HSV-1 antigens. Blast transformation assays combining antigens from two different herpes viruses or combinations of measles and herpes antigens showed no synergy. The obtained data indicate a pronounced synergistic effect on the cellular immune response when retrovirus and herpes antigens are present together. The cause of the synergy is unknown so far. The effect on the immune response may influence the disease progression.

Adult↗
PubMed2003

[Human endogenous retroviruses and disease?].

Endogenous retroviruses represent sequences descended from ancient virus infections integrated in the host genome. They participate in processes, such as speciation, recombination, ontogenesis, and regulation of tissue specificity and gene expression. It has been suggested in recent years that human endogenous retroviruses may play a role in certain types of cancer and autoimmune diseases. Human endogenous retroviruses represent both putative susceptibility genes and putative pathogenic viruses in diseases like systemic lupus erythematosus, Sjögren's disease, rheumatoid arthritis, and possibly type 1 diabetes. Multiple sclerosis is specifically associated with expression of human endogenous retroviruses as virions. It is not yet known if the human endogenous retroviruses also represent causal factors, but several pathogenic mechanisms are possible.

Arthritis, Rheumatoid↗
PubMed2002

A transmissible human endogenous retrovirus.

The transmissibility of the human endogenous retrovirus HERV-H/RGH-2 was investigated by marker rescue: intraspecies transmission of HERV-H/RGH-2 retrovirus particles was attempted by cocultivation of virion-producing, long-term cell cultures spontaneously formed from peripheral blood mononuclear cells from several multiple sclerosis patient cultures with a retroviral vector construct-harboring cell line. Transmissibility was assessed by assays for productive infection (reverse transcriptase activity), and assays for rescue of the retroviral vector construct in indicator cells. Our studies show that the human endogenous retrovirus HERV-H/RGH-2 is transmissible, albeit at a very low level. The human endogenous retrovirus HERV-H/RGH-2 is associated with multiple sclerosis (MS). Previously, we demonstrated sequence variants of the human endogenous retrovirus HERV-H family in virion form, by applying RT-PCR to virion RNA from the supernatants of long-term MS cell cultures, and to the particulate fraction of a series of MS patient plasma samples.

Cell Line↗
PubMedDate not supplied

Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses.

The hypothesis that human endogenous retroviruses (HERVs) play a role in autoimmune diseases is subject to increasing attention. HERVs represent both putative susceptibility genes and putative pathogenic viruses in the immune-mediated neurological disease multiple sclerosis (MS). Gammaretroviral HERV sequences are found in reverse transcriptase-positive virions produced by cultured mononuclear cells from MS patients, and they have been isolated from MS samples of plasma, serum and CSF, and characterised to some extent at the nucleotide, protein/enzyme, virion and immunogenic level. Two types of sequences, HERV-H and HERV-W, have been reported. No known HERV-H or HERV-W copy contains complete ORFs in all prerequisite genes, although several copies have coding potential, and several such sequences are specifically activated in MS, apparently resulting in the production of complete, competent virions. Increased antibody reactivity to specific Gammaretroviral HERV epitopes is found in MS serum and CSF, and cell-mediated immune responses have also been reported. Further, HERV-encoded proteins can have neuropathogenic effects. The activating factor(s) in the process resulting in protein or virion production may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS.

Antibodies, Viral↗