Multiple Sclerosis: The Immunological Features

Multiple sclerosis (MS) is an unending demyelinating disease (Matsui, 2008) of the central nervous system (CNS) comprising of the brain and spinal cord. It is also an inflammatory disease that causes damage to the immunity to CNS. In general, it initiates at a young age between 20 and 40 and causes severe disability through discrepancy of sensation and of motor, autonomic, and neurocognitive function (McFarlin and McFarland, 1982).

Several scientific approaches to explain the immunopathogenesis of this disorder have been carried out over the past several years, but it has not been possible to specify the target antigen that is responsible for the attack on the immune system in patients with MS (Matsui, 2008). Attempts have also been done to classify MS based on its occurrence and also its progression. Relapsing-remitting (RR)-MS is the most common form of MS as it is responsible for about 85%–90% of all cases. It is more common in women than in men. It is also observed that most RR-MS patients later develop secondary progressive (SP)-MS. The rest 10%–15% of patients with MS present with dangerous beginning and steady development and is called primary progressive (PP)-MS.

Even today the debate is still on regarding the immunological features of MS. There have been several studies that point out that MS is a CD4+ Th1-mediated autoimmune disease (Martin, et al. 1992; Hafler, 2004). This came into the picture with the study of the cellular composition of the brain and cerebrospinal fluid infiltrating cells. Additionally, the data from experimental allergic/autoimmune encephalomyelitis (EAE) also pointed out this fact (Zamvil and Steinman, 1990).

According to this EAE model when the susceptible animals were injected with myelin components it resulted in a CD4+-mediated autoimmune disease and is very similar to MS (Martin, et al. 1992; Zamvil and Steinman, 1990). Further, it was also noted that it can be adoptively transmitted by encephalitogenic CD4+ T cells into an immature animal (Pettinelli and McFarlin, 1981). There are also studies that point out the role of genetic factors. Though the role of CD4+ T cells in MS is further confirmed by many, it is also advocated in some way by the fact that certain HLA class II molecules correspond to the high-proof genetic risk factor for MS, most likely through their function as antigen-presenting molecules to pathogenic CD4+ T cells (Sospedra and Martin, 2005).

According to a study it was found that the immunological factors of MS are linked with genetic predisposition that includes a strong connection with the HLA-DR2 haplotype. The second one is linked with a high prevalence of disease in higher latitude regions of the world.

This indicates that some environmental factors may also be a cause for MS. Studies point out that temperature and climate change together with latitude may promote the infectious agents, particularly viruses that may have a role in the pathogenesis of MS prevalent in higher latitudes. However, these two factors i.e. the genetic and the latitude is not mutually exclusive. For instance, a particular type of immune reaction to some viruses, intended for by HLA-DR2, may consequence in autoimmunity to CNS myelin proteins (Wucherpfennig and Strominger, 1995).

Even though the etiology of MS is still uncertain, according to recent studies it is said that the disease initiates in genetically susceptible individuals and may need additional environmental triggers for the manifestation of MS. Several studies that included different population, family, and twin studies indicated a genetic link as the occurrence increased in family members of MS patients. Further in-depth studies pointed out that first-degree relatives or the immediate relatives of affected individuals have an roughly 20- to 50-fold greater risk to develop MS. It was also found in monozygotic twins that the concordance rates are about 25% (Dyment et al. 2004).

The look for individual susceptibility genes has not yielded much result despite incredible advance in the technology. As of today it is only been possible that one or more susceptibility genes on chromosome 6p21 in the area of the major histocompatibility complex is thought to account for 10%–60% of the genetic risk of MS (Hillert and Olerup, 1993). It is only possible through further research that the scientific community will be able to make further progress in identifying the immunological features of MS.

References

Dyment, D.A, Ebers, G.C and Sadovnick, A.D. 2004. Genetics of multiple sclerosis. Lancet Neurol. 3:104–10.

Hafler, D.A. (2004). Multiple sclerosis. J.Clin. Invest. 113:788–94.

Hillert, J. and Olerup, O. 1993. HLA and MS. Neurology 43:2426–27.

Martin, R., McFarland, H.F. and McFarlin, D.E. (1992). Immunological aspects of demyelinating diseases. Annu. Rev. Immunol. 10:153–87.

Matsui, M. (2008) Multiple sclerosis immunology for clinicians, Neurology Asia; 13:195 – 198.

McFarlin D.E. and McFarland H.F. (1982). Multiple sclerosis (first & second part). N. Engl. J. Med. 307:1183–88.

Pettinelli, C.B. and McFarlin, D.E. 1981. Adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice after in vitro activation of lymph node cells by myelin basic protein: requirement for Lyt 1+ 2-T lymphocytes. J. Immunol. 127:1420–23.

Sospedra, M. and Martin, R. (2005) Immunology of Multiple Sclerosis, Annu. Rev. Immunol. 23:683–747.

Wucherpfennig K.W. and Strominger, J. (1995) Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T cell clones specific for myelin basic protein. Cell; 80:695-705.

Zamvil, S.S. and Steinman, L. 1990. The T lymphocyte in experimental allergic encephalomyelitis. Annu. Rev. Immunol. 8:579–621.