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2005 First Paper
Multiple Sclerosis: Auto-Immunity and Genetics
This paper is an exploration into the complexities of autoimmune disorders, in particular those related to multiple sclerosis. An additional focus is on the interplay between external factors such as one's environment and genetics in order to better understand the concept of auto-immunity. These questions lead us to a further question of the role of science and in what ways does science help in making new discoveries? Given that there is no known cause or cure for MS, in what ways, if any, is science adequate in understanding the complexity of autoimmunity?
MS is a well-documented disease, affecting around 300,000 Americans and is second only to head trauma as the most common neurological cause of disability among young adults (4). Symptoms of the disease vary widely but they generally include numbness of the limbs, fatigue, double vision and/or loss of vision, imbalance, incoordination, speech problems, loss of motor control and chronic pain (4). These symptoms can be chronic as is the case with MS victims of the progressive type or they can be intermittent as in those patients with relapse-remitting MS (4). The fact that these symptoms vary drastically, among individuals but also within the individual course of the disease, is one of the reasons that MS is so hard to treat. There is drug treatment but patients often respond differently, or not at all, and severe side effects may result (7).
While the symptoms of the disease vary, the population it attacks does not: the majority of MS sufferers are women of Northern European heritage (7). There is an extremely low prevalence of MS in populations of African blacks, Asians and ethnic groups with little Caucasian mixing.This is where the field of genetic becomes crucial; by researching and comparing chromosomal sites of MS victims and their families, these studies seek to address the question of why MS is so prevalent among Caucasian women between the ages of 20 and 50 (7).
In order to understand genetic studies involving MS, one has to first understand how the disease itself functions. MS is characterized by lesions on the brain, inflammations which occur due to demyelination. Myelin is a combination of lipid fats (80%) and proteins (20%) which sheath the axons, or nerve cells, in the central nervous system (7). Myelin affects the speed with which nerve signals (impulses) can move down the axons. In MS, this myelin is destroyed and can no longer act as an axon sheath, inhibiting the transmission of nerve signals and also leading to partial or total nerve damage . Myelin is destroyed by T-cells which recognize myelin as a foreign body and therefore destroy it; it is this process in which the body actively attacks its own cells which led to the designation of MS as an
autoimmune disorder (7).
Genetic research is essential to understanding MS. It is a complex disorder, meaning that it is multifactorial and polygenic: it does not strictly follow Mendelian patterns of inheritance because there are multiple, interacting genes involved (3). This is complicated by the belief that each gene contributes relatively little to overall risk of susceptibility; it is only in the specific way in which these genes interact with one another and with the environment which triggers the onset of MS (3). Scientists have, however, been able to locate eight regions of interest at chromosomes 5, 6, 17 and 19. The regions are singled out as showing linkage to MS and were derived from family-based association studies which examine which alleles are transmitted to children through a test called the transmission-disequilibrium test (2). The interaction of multiple genes is further complicated by the fact that primary genetic heterogeneity can occur in those affected by MS, meaning that different genes can cause similar and even identical forms of MS (2).
Another interesting way in which genes are important to MS research lies in the
differentiation between susceptibility genes and modifier genes. For example, the HLA-DR2 haplotype at chromosome 6 has shown linkage to MS because of the way HLA alleles (a DNA coding of a single gene), respond to antigens (proteins) (2). These genes may not only influence susceptibility but also clinical symptoms such as how the disease develops and progresses and how patients respond to drug therapies. For instance, studies have shown that there is an association between the apolipoprotein-4 allele and the severe MS strains . Similarly, those patients in this group study who suffered from mild strains of MS contained a larger percentage of the APOE-2 allele carriers (2). This means that a carrier of a certain allele may experience symptoms differently than someone who carries a different allele.
Additionally, past studies conducted on twins shows a linkage between genetic make-up and disease susceptibility. For example, the rate of susceptibility of the general population is 0.1% while for siblings and fraternal twins it is about 5% . But while there is an increased susceptibility for those related to MS victims, genetics is not the exclusive factor. If that were so, there would be a concordance rate of nearly 100% for identical twins. This is not the case. This suggests then that genetics may contribute to susceptibility but there are other environmental (and unknown) factors which trigger the onset of the disease. This trigger is as yet
unknown but is believed to be a virus or bacteria of some sort. The Multiple Sclerosis Genetics Group puts it thus, "....it is also likely that interactions with infectious, nutritional, climatic, and/or other environmental influences affect susceptibility considerably. This complex array of factors results in a severe disregulation of the immune response, loss of immune homeostasis and self-tolerance..." (7). In other words, while scientists have been able to identify linkage in certain chromosomal regions, the complex interplay of factors which affect such things as age at disease onset, intensity and duration of symptoms and reaction to drug therapy, combine in such a way to make MS unpredictable.
An additional point of interest that this citation brings forth is the idea of "self-tolerance" or auto-immunity. How exactly does one respond or deal with instances when the body actually turns on itself? This is the question which science now has to try to answer. There is treatment for MS but there is no cure or any known cause. This leads us to the question of the role of science and more specifically, are there some questions which science simply cannot answer?
As one Biology student comments in her paper "MS and the Self": "People guard their
mental functioning closely. However, when the cognitive problems of MS set in, they may find that they have lost hold of that which they consider to encompass "self" (1). Her point is a good one in that it comments on the psychological implications of this disease which is at once mentally and physically debilitating. It is also profoundly debilitating psychologically due to its inherent unpredictability. The occurrence of MS and other autoimmune disorders directs our focus to the workings of the human body, those biological processes which (healthy) humans take for granted. It is these processes which we are unaware of; like breathing and winking, the body performs numerous and intricate tasks without us even realizing. But what happens when the possibility of malfunction, of human error in a quite literal sense of the expression, takes place? This is the most debilitating realization that can be drawn:
the realization that one's body and its mechanics are faulty, that what is "alien" and what is "self" are not distinguished by the brain. Here is a breakdown of communication at the most basic level- not between individuals, but within them, at the cellular level. And all this is beyond one's control.
In conclusion, some comments were made in the course forum area which described
science as useful despite its weaknesses. We can debate its truthfulness or its accuracy but its utility as a way to describe and understand how and why things happen remains essential (5). This is true even in the case of MS. There may be gaps in scientific knowledge but this is not to say that science loses its value as an exploratory tool. Studies in MS have shown how scientific research leads to new questions which lead to further research. Although many questions concerning MS remain unanswered, these unanswered questions lead to further explorations in the field of auto-immunity.
Sclerosis and the Self, can be found on Serendip website.
Sclerosis as Genetic Disease.
4)Multiple Sclerosis: The Immune System's TerribleMistake.
5)Biology 103 Forum area, on the Biology 103 website.
Genetics- The Basic Facts, on the National MS Society website.
7)Send us your comments at Serendip
Research Directions in Multiple Sclerosis, on the National MS Society website.
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