A new theory on autoimmunity with reference to multiple sclerosis
- PDF / 449,939 Bytes
- 4 Pages / 595.276 x 790.866 pts Page_size
- 0 Downloads / 215 Views
INTERPRETIVE SYNTHESIS REVIEW ARTICLE
A new theory on autoimmunity with reference to multiple sclerosis Bjørn A. Nexø 1
# Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract Recent genetic evidence points towards endogenous retroviruses as playing a pivotal role in the causation of multiple sclerosis and possibly other autoimmune diseases. We discuss various ways in which this association could be brought about. Specifically, we suggest that two endogenous retroviruses, HERV-Fc1 and HERV-K13, on chromosomes X and 19, respectively, contribute to the development of autoimmune T cells by transforming them in multiple sclerosis. Partially overlapping sets of endogenous retroviruses may play a role in other autoimmune diseases. If this theory holds true, many scientists may have looked for viruses in the wrong tissue. Ir would also explain why lymphocyte-suppressive agents suppress multiple sclerosis. Keywords Endogenous retroviruses . Autoimmune diseases . Multiple sclerosis
Two major theories prevail about the causation of demyelinating diseases: The disease could be caused by retroviruses or it could be caused by inflammation and autoimmunity. In addition, there is epidemiological evidence that vitamin D and EBV play a role. We now propose a way of thinking that combines the two major theories: Retroviruses cause demyelinating diseases not because they themselves cause CNS cell decay but because they cause proliferation of specific immune cells, which provoke a reaction in the CNS. The theory also leaves room for a role of Vitamin D and EBV. It is certain that retroviruses can cause diseases similar to multiple sclerosis (MS). The classical example is Visna of sheep [1] caused by a retrovirus related to HIV. Newer examples are hind leg paralysis of mice caused by Lake Casitas virus [2], and human tropical spastic paraparesis [3] caused by human T cell leukemia virus (HTLV) in African, Caribbean, and Japanese populations. Indeed, CNS complications are common in patients with infection with human immunodeficiency virus (HIV) [4]. Visna and TSP appear to involve demyelinization [5–7], while the situation is more uncertain for Lake Casitas disease and HIV. Endogenous viruses are retroviral sequences embedded in the host germ-line DNA, presumably as a consequence of past
* Bjørn A. Nexø [email protected] 1
Department of Biomedicine, Aarhus University, Vilhelm Meyers Alle 4, DK-8000 Aarhus C, Denmark
infections of the germ line. The viral loci are now transmitted as Mendelian entities. The human genome contains in the order of 100,000 such loci distributed on all chromosomes but most sequences are grossly defective, and only about 50 loci are able, with one or two mutations, to encode a viral protein [8]. Very few, if any, human endogenous retroviral sequences are complete. However, recombination between endogenous viruses happens in animals [9, 10], and in these, it leads to replication competent and sometimes pathogenic entities. MS is a severe human demyelinating disease of the central ner
Data Loading...
