Amy Ballard

Eng. 232
Semester Paper: Autoimmune Diseases
This paper will focus on articles dealing with various autoimmune diseases. These
diseases are a result of the immune system reacting to and attacking an individuals own healthy
tissue. The paper will discuss autoimmune diseases as an entire group as well as looking
specifically at Lupus, Multiple Sclerosis, Behet's Disease, and Rheumatoid Arthritis. I chose
this topic because I was diagnosed with Behet's Disease at the age of nineteen. It took five years
to diagnose and was confused for many other diseases during that time. Because of this, I have
taken an interest in the similarities, differences, and possible relationships between the numerous
autoimmune diseases.
Thomas, Sara L., Clare Griffiths, and Andrew J. Hall. "Burden of Mortality Associated with
Autoimmune Diseases Among Females in the United Kingdom." American Journal of
Public Health 100.11 (2010): 2279-2287. Web. 19 Apr. 2014.
<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951969/>.
This article addresses the way in which autoimmune diseases are neglected in the
International Classification of Diseases (ICD) system. The ICD groups conditions based on
pathogenic mechanism (e.g., neoplasms), organ system (e.g., diseases of the circulatory
system), or etiology (e.g., external causes of death). Autoimmune diseases are typically listed
under separate organ systems and so the actual number of deaths due to autoimmune diseases
each year is not readily known. This study concluded that autoimmune diseases are in fact a
leading cause of death among females in both England and Wales. However, the collective
impact of these diseases is still not known due to the classification system.

This study was carried out by gathering all of the mortality files registered in England
and Wales between 1993 and 2003. From these files, they selected deaths among females of at
least 1 year of age. All records indicated the year of death registration, the age of the deceased,
and multiple causes of death, including the designated underlying cause of death. They
narrowed the selection down even further by picking out files in which an underlying cause was
attributed to at least one of 24 specific autoimmune diseases, or to an unspecified autoimmune
disorder. They then coded the deaths so as to include them in an already existing
categorization/ranking system. They discovered that during this time there were 283,236
registered female deaths in England and Wales. Among those deaths an autoimmune disorder
was mentioned on the death certificate in 9,271 cases and was listed as the underlying cause of
death in 4,420 cases. By using this data they were able to determine that autoimmune diseases
are among the 10 most frequent underlying causes of death for females in all age groups
between 1 and 75 years in England and Wales.
The lack of readily available information prevents autoimmune diseases from getting the
chance to be ranked as a leading cause of death, and therefore preventing it from receiving ample
research as other diseases do. This study, ranking it among the top 10 underlying causes of death
in females, reveals what a large issue this could be. The study explains that the higher a disease
or group of diseases ranks, the more likely policymakers are to do something about it, by
bringing awareness, funding research, or ensuring public access to information. The article
expounds further on the ranking system as a whole asking the reader to consider what other
diseases may not be accounted for accurately. Just as some may be counted to few times or
neglected in the ranking system, there are some that may have too many mortalities attributed to

them. Regardless, it is important that a variety of factors be looked at when ranking cause of
death and making decisions based on that.
Kuehn, Bridget M. "Scientists Probe Strategies to Repair Neuron Damage in Multiple
Sclerosis." Journal of the American Medical Association 305.9 (2011): 871-874. Web. 22
Apr. 2014.
<http://jama.jamanetwork.com.prox.lib.ncsu.edu/article.aspx?articleid=645904&author=
Kuehn>
Multiple sclerosis is a progressive disease resulting from damage to the nerve cells in the
brain and spinal cord. Some of the most common symptoms are blurred vision, impaired speech,
and impaired muscle coordination and strength. This article details the efforts being made in
hopes of repairing neuron damage in patients with multiple sclerosis.
There are a variety of treatments aimed at tamping down aberrant immune function and
reducing specific symptoms. However, in 2011, several groups reported that they have
developed sufficient evidence from animal- and tissue-based studies to begin safety trials of
agents that may help to restore some function in patients who have experienced neurologic
impairments from MS. One team of researchers did experiments with rats and mice by blocking
RXR- agonist from the brain or administering it and looking at the results. They found that by
administering RXR- they were able to direct the brain's endogenous repair mechanisms thus
giving them hope that something similar could be done with people. Creating this response in
people would essentially mean to activate stem cells in the brain to kick-start the repair
process.

This is significant because it would not simply treat symptoms, or help patients to cope
with the symptoms, but it would actually restore the nerves responsible for those symptoms.
However on researcher, Giovannoni, MD, PhD, cautioned that it's important for patients and
physicians to have realistic expectations about when such therapies might become available.
The research detailed in this article puts us leaps and bounds ahead of where we once were, but it
took years to put together and will take many more years to be realistically useful. Therefore, the
consensus groups reached several conclusions: First that Preliminary clinical trials of
mesenchymal and neural precursor cells to treat progressive MS should be considered. Trials of
such prospective therapies should follow the guidelines of the International Society for Cellular
Therapy and the International Society for Stem Cell Research and that All such trials should be
registered and data and methods shared. For the next four to five years, the goal is to determine
the safety of these cells and until then patients should be discouraged from seeking care at
stem cell clinics offering treatments that do not follow the groups recommendations.
Stone, John H. "BLISS! Lupus Learns Its Lessons." Lancet 377.9767 (2011): 693-694. Web. 23
Apr. 2014.
<http://www.sciencedirect.com.prox.lib.ncsu.edu/science/article/pii/S0140673610615462
>.
This article covers a clinical trial, BLISS-52, targeted at Systemic lupus erythematosus.
This disease is incredibly difficult to diagnose, and has been the subject of many failed clinical
trials. This specific trial being discussed was successful because of a few things that it did
differently. First, it included patients with serologically active disease meaning the patients
were currently having a flare up and were in need of improvement. Second, it addressed

disease-assessment indices. Finally, the protocol took rational measures to ensure that the
treatment effects of belimumab were not obscured by concomitant SLE therapies.
The trial was made difficult by a number of factors. One such factor is the fact that it is
very difficult to enroll patients suffering from the disease. Because it is not a particularly
common disease, the study has to take place in many different locations. Another difficulty is
trying to ensure that improvements in disease in some organs should not be accompanied by
worsening of other disease manifestations. Multiple indexes had to be used to in order to do
this, as well as to make sure all improvements were measurable. The study also had to be done
over a fairly long period of time, which presents its own difficulties with funding and
maintaining all of the guidelines set at the beginning of the study. In the end The trial showed
consistent effects on clinical efficacy, serological activity, and glucocorticoid reduction; it
showed strong evidence for a dose response to belimumab; and it provided reassurance of
safety.
While these results are significant, the article points out that the methods by which they
accomplished this were more significant. This is one of the few successful trials in Lupus
research and will now set the standard for other clinical trials. Ideally, the findings of this trial
will lead to other successful studies so that this information can come to some practical benefit.
However, even without these findings, if other researchers mimic the methods used in carrying
out this trial then Lupus research may make great progress in the coming years. Researchers and
patients alike hope that a new era for lupus therapies has dawned.
Noel, N., Wechsler, B., Nizard, J., Costedoat-Chalumeau, N., Boutin, D. L. T. H., Dommergues,
M., Vauthier-Brouzes, D., Cacoub, P. and Saadoun, D. Behet's Disease and

Pregnancy. Arthritis & Rheumatism. 65.9. (2013) 24502456. Web. 19 Apr. 2014.
<http://onlinelibrary.wiley.com.prox.lib.ncsu.edu/doi/10.1002/art.38052/full>.
Behcets disease (BD) is a rare autoimmune disease resulting from inflammation in the
blood vessels. It is characterized by a wide variety of symptoms, however most patients will
experience a group of three symptoms during a flare up. This study addressed the interplay
between flare ups before, during, and after pregnancy. The study was done retrospectively using
patient interviews and medical records. The study concluded that most women with BD
improved during pregnancy, though 35% saw a worsening of the disease during pregnancy.
The study was conducted with 46 patients reporting on 76 different pregnancies. Each
patients health before becoming pregnant was used as their norm by which to judge the
pregnancy and postpartum stages. Most patients experienced less flare ups during pregnancy,
with symptoms limited to oral, ocular and genital lesions. Only a few patients worsened or
experienced life-threatening complications such as thrombosis or CNS lesions during their
pregnancies. However, many patients reported worsening after pregnancy. It is believed that
some of this was a result of a vaginal birth, which can irritate the general area and cause genital
ulcers, but some if may have to do with treatment. Most patients who did not see a worsening of
the disease were treated with colchicine. Some patients were not given this drug because of the
possible risk to the baby, as it does cross the human placenta.
Complications with the birth and baby were also addressed in this study. There was an
overall rate of obstetric complications of 26.2% in patients with BD. While this is not the
majority of pregnancies, it is still a significant number, especially considering that these
complications consisted mainly of miscarriages, which could be related to the existence of

decidual vasculitis in BD. Miscarriages are clearly an enormous complication that researchers
hope to address in future studies. The most significant result of this study is likely the
information dealing with the colchicine. Though researchers acknowledge the possibility of
complications involved with this treatment, none have actually been seen as a result of using it.
Hopefully, this treatment can continue to be beneficial to patients and those of us with BD can
experience relatively normal pregnancies in the future.
Friedrich, M J. "UV Light and MS." The Journal of the American Medical Association 303.17
(2010): 1686. Web. 24 Apr. 2014.
<http://jama.jamanetwork.com.prox.lib.ncsu.edu/article.aspx?articleid=185783>.
Multiple Sclerosis (MS) is more common in higher latitudes, and farther inland than it is
around coasts and the equator. There are a number of theories surrounding this. Some believe
that it is related to diet, and others that it has more to do with UV light and vitamin D. This
article explains that new studies in a mouse model of MS suggest that UV light may play a
bigger role than vitamin D in controlling symptoms of MS.
Past studies have revealed that a combination of UV radiation and large doses of Vitamin
D can suppress the disease in models in using mice. However, in the study being discussed
researchers relied on the UV radiation and only very modest levels of Vitamin D. By doing this
they found that use of continuous treatment with UV radiation to simulate tropical conditions of
sunlight dramatically reduced clinical signs of EAE. As the levels of Vitamin D were not high
enough to account for this, they determined that compounds in the skin might be stimulated by
UV radiation to bring about the suppression of disease symptoms.

It is important to note that they do not believe that they have found a cure for the disease,
but rather a way of suppressing the symptoms and sending it into remission. This method may
pose other problems, though. UV radiation is commonly linked to cancer, which would be an
extreme risk in using this treatment. For this reason, it will likely take quite a few years before
clinical trials of this treatment are even suggested. However, that does not mean that this
information cannot be used already. Patients who currently have MS can make an effort to spend
moderate amounts of time outside and in the sunlight. This in conjunction with an intake of
Vitamin D could make a world of difference for some patients, especially those who are
diagnosed at an earlier age.
Hampton, Tracy. "Researchers Probe Lupus Causes, Treatments." The Journal of the American
Medical Association297.2 (2007): 141-142. Web. 24 Apr. 2014.
<http://jama.jamanetwork.com.prox.lib.ncsu.edu/article.aspx?articleid=205009>.
Systemic lupus erythematosus (Lupus) causes a plethora of different symptoms and is
often mistaken for different diseased for years before it is accurately diagnosed in a patient. Not
surprisingly, it is also very difficult to determine a cause for the disease, and none has yet been
found. This article discusses some of the research and theories that are currently being
considered.
One group of researchers looked into the reason that lupus is found in women 10 times
more often than it is found in men. In every somatic cell of a woman's body, one of the 2 X
chromosomes is randomly silenced. These researchers theorized that if genes on a silenced X
chromosome become active, the individual will be predisposed to the disease. They decided to
look at the CD40 ligand specifically. This is a molecule that plays a role in inflammatory

processes and antibody production, is overexpressed on T cells of women with lupus. The gene
for coding the CD40 ligand is on the X chromosomes. As they studied this they discovered their
predictions to be right; this molecule is overexpressed uniquely in women with lupus. This
causes one to question what other genes on the X chromosomes may contribute to Lupus.
Perhaps it will be studying this further that gets researchers to the cause of the disease.
Another group of researchers believe that there may be a link between Lupus and the
immune systems response to microbial infections. TLR7 is part of a family of receptors that
triggers innate immune reactions in humans and other animals to counter microbial infections.
When TLR7 is duplicated it becomes more responsive to these infections. The problem arises if
something in the duplication of these TLRs goes wrong. Studying this duplication process has
read researchers to believe that lupus arises at least in part due to errors made by TLRs in
discriminating between self and microbes. Essentially, the immune system begins to attack the
body in various ways, as well as the microbes.
It may be one of these theories, a combination of them, or neither that is correct.
Regardless, it is hoped that by searching for a cause rather than treatment of symptoms we can
learn to prevent the disease. It is currently known that the antibodies are present for about 3 years
before symptoms start to show. If doctors are even able to detect some of these aforementioned
problems and diagnose the disease before symptoms ever arise, countless lives will be changed
for the better.
Scott, David L., Frederick Wolfe, and Tom W. Huizinga. "Rheumatoid Arthritis." The
Lancet 376.9746 (2010): 1094-1108. Web. 25 Apr. 2014.

<http://www.sciencedirect.com.prox.lib.ncsu.edu/science/article/pii/S0140673610608264
>.
Rheumatoid Arthritis (RA) is an autoimmune disease characterized by synovial
inflammation and joint destruction. This disease affects vast numbers of people all over the globe
though criteria for classifying it was only developed 50 years ago. This article attempts to
compile all of the most basic and important information regarding the disease today.
Although the article acknowledges that half of the disease is due to genetic factors, it
does suggest some ways of preventing it. The first suggestion would be to decrease the number
of people who smoke. It is first important that the individual not smoke as that increases the risk
of developing RA greatly. It is also important, though, to decrease smoking among the general
population as second hand smoke is still a contributing factor. The article additionally suggests a
healthy diet, though insufficient evidence exists to support this idea. Perhaps a reason this was
still included in the article is the necessity for patients with RA to maintain a healthy weight. As
the disease takes a toll on joints it is important the patients avoid adding excess stress to the
joints that comes with excess weight.
The article gives additional information addressing continuing research and future
perspectives. One key need is definition of disease subsets in individuals with early arthritis so
that intensive treatment regimens can be targeted at patients who most need them and are likely
to respond. As is, treating individuals with RA is a bit of a guessing game in that there is one
diagnosis and no way to individualize treatment except by trial and error. The article also
expresses the need for more short intensive therapeutic courses that promote remission, rather

than long-term suppressive treatments. This would ideally be more manageable for patients and
risk less side effects. That is the primary goal right now: to help patients.
"Advances in Autoimmune Rheumatic Diseases." The Lancet 382.9894 (2013): 744. Web. 25
Apr. 2014. <http://ac.els-cdn.com.prox.lib.ncsu.edu/S0140673613618164/1-s2.0S0140673613618164-main.pdf?_tid=48df3478-ce4f-11e3-ae4000000aab0f27&acdnat=1398632747_d29f68025b58cef77d34d4654baacb35>.
While there is a lot of research being done on specific autoimmune diseases, there is also
research on the group as a whole. Some people have great interest in the similarities between
them and hope that methods of diagnosing and treating them can be shared between diseases on
some level. This article reviews several recent studies on the group of diseases and what came of
them.
The first paper discussed, by Fiona Goldblatt and Sean ONeill, deals with
developments in understanding the clinical features of several autoimmune rheumatic diseases.
It is acknowledged that many of these diseases share features and that is part of what makes them
so hard to diagnose. However, the number of autoantibody tests is growing, which should
improve the speed and accuracy of diagnosis. These tests are helping to create more specific
criteria for classifying these diseases. This is extremely significant because of the high mortality
rate associated with these diseases. The earlier a patient can be accurately diagnoses, the earlier
he or she can receive appropriate treatment. Often times, this makes all the difference in
determining quality of life.
The second paper discusses the biological treatment of autoimmune rheumatic diseases,
with a particular focus on systemic lupus erythematosus. The authors of this paper explain that,

in clinical trials, success has been seen in treating lupus patients with belimumab. However, the
results are not on part with those of rheumatoid arthritis. For this reason, it is important not to
settle for this treatment. There is evidence, seen in the RA trials, that this treatment has the
potential to do a lot of good, and it is not doing that for lupus patients. Therefore, more can still
be done. Researchers need to look beyond this and continue to target treatments at lupus rather
than piggy-back off of an RA treatment.
The final study discussed is in regards to non-steroidal anti-inammatory drugs
(NSAIDs). These are currently the most popular option for treating autoimmune diseases. Most
patients using these drugs do not experience severe side-effects; however there are vascular and
gastrointestinal risks. These risks will have to be a major consideration as researchers look
further into the development of these drugs.
There are a few ways in which these issues could be related to Gilmans story, The
Yellow Wallpaper. The first of which relates the article, "Burden of Mortality Associated with
Autoimmune Diseases Among Females in the United Kingdom." Though it is for different
reasons, both issues are or have been generally overlooked. Gilmans story expresses the way in
which postpartum depression did not get the attention it deserved, just as this article proves that
autoimmune diseases are somewhat neglected. Some of this belief is even manifested in
Gilmans main character when she says, I am glad my case is not serious! (Gilman 3). This
shows how even she has come to believe that her condition does not deserve more attention.
Similar to this, Gilmans character does not receive treatment specific to her, and is diagnosed
with general hysteria. A lupus patient reading the article, Advances in Autoimmune
Rheumatic Diseases, may feel a bit like this knowing how few successful clinical trials there

have been regarding lupus, and how some of the most promising treatments were not initially
intended for them.
Autoimmune diseases parallel this story in their great needs for advancement in diagnosis
and treatment. However, this story was able to get attention and bring about real changes for
women with postpartum depression. With any luck, some of the literature and research being
done on various autoimmune disease will yield similar results.