The Chronic(als) of Autoimmunity

Kirsteen Maclean on September 25, 2018

Political climate aside, life in Britain in the 1930’s and 1940’s was harsh and infectious disease (particularly tuberculosis) was one of the most urgent health problems; such infections favored the overcrowded, unsanitary environments prevalent in many of Britain’s cities at the time. Without successful treatments options the mainstay of care was limited to bed rest and confinement to a sanatorium to avoid the spread of infection.

Following the death of her father to what was then called consumption in the early 1940’s, a young girl exhibiting early signs of tuberculosis infection was committed to a local sanatorium, and there she stayed until the onset of a revolutionary new antibiotic, streptomycin. Whilst revolutionary in terms of its effects in paving the way forward to a sharp decline in the disease and saving this young woman’s life, long term antibiotic usage proved to have consequences later. By middle age the woman began exhibiting symptoms of various autoimmune disorders such as inflammatory bowel disease, thyroid issues and rheumatoid arthritis. This woman was my mother.

Were the antibiotics to blame1 for altering her gut flora? Or was the cause rather a combination of many factors that we know today can affect the balance of our immune system that contributes to the onset of these chronic disorders?   Herein belies the issue with autoimmunity. There is to date no cure but plenty of causes that I will allude to. Sadly, for my mother, years of palliative treatment options merely relieving the pain resulted in the onset of dementia and ultimately, Alzheimer’s Disease, from which she passed away from. Of course, the jury is still out as to whether her childhood infection was the root cause of her subsequent autoimmune insult and whether a general inflammatory response was the cause of her dementia; however, there is recent evidence to link them all.

My name is Kirsty Maclean, PhD, and I’m the Principal Application Scientist for NanoString Technologies. For many years as a post-doctoral researcher and beyond, I studied oncogene-mediated tumorigenesis and its impact on the immune repertoire driving pro-inflammatory cytokines (albeit in a time prior to our knowledge on the genome and using what would now be considered very rudimentary techniques). It is serendipitous that at NanoString® we can explore the immune function in a much more comprehensive manner using a series of highly curated gene expression panels for any application area within autoimmune research. In this blog, the first in a series covering all aspects of autoimmunity, I’ll discuss some of the general trends and its prevalence in research and therapeutics today.

Autoimmunity is a blanket term used to describe almost 80 unique illnesses that include, but certainly are not limited to, Multiple Sclerosis, Systemic Lupus Erythematosus, Type 1 Diabetes, Psoriasis and Rheumatoid Arthritis. It is characterized by the immune system targeting good, helpful, healthy tissue as being foreign and thus sustaining an immune response to it, ultimately causing organ deterioration and destruction. There can be a wide array of symptoms, but inflammation is nearly always the key indication. Interestingly, autoimmune disorders tend to be more common in women (an area that I’ll focus on in future blog posts) with estimates of as many as 9 out of 10 women being afflicted with certain conditions such as lupus 2. As previously suggested, all autoimmune disorders are chronic, most have no cure, and other than cancer, can be some of the most expensive diseases to treat. In that regard (at least in the US) one cannot fail to notice the dramatic increase in television advertisements geared towards pharmaceutical approaches to various autoimmune disorders. These drugs include etanercept (Enbrel), adalimumab (Humira) and infliximab (Remicade) and are prescribed to treat various autoimmune conditions such as Crohn’s disease, inflammatory bowel disease, rheumatoid arthritis and psoriasis. It may be a surprise to learn that the top selling prescription drug in the US is not related to oncology or heart disease but inflammation3.

The research in this field has exploded and using the search term “autoimmunity” in PubMed will reveal over 42,000 publications, 2,000 in 2018 alone. Unfortunately, the true cause(s) of autoimmune disease remains elusive, but there are many indicators as to a potential smoking gun. Surprisingly, autoimmunity occurs naturally in everyone to some degree, and in most people it does not result in disease. Autoimmune diseases instead occur progressively over persistent periods of time when there is some interruption of the usual control process, allowing lymphocytes to avoid suppression, or when there is an alteration in some body tissue so that it is no longer recognized as “self”. The exact mechanisms causing these changes are not wholly understood but culpable contenders include bacteria, viruses, toxins, food, the environment and some drugs, all of which may play a role in triggering an autoimmune process in someone who already has a genetic predisposition to develop such a disorder. It is theorized that the inflammation initiated by these agents, toxic or infectious, somehow provokes the sustained reaction in the involved tissues.

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Post by Kirsteen Maclean