Posted by Written by Kaushik Eswaran
In decades past, a cross section of medical ailments found in India would contain many of the usual suspects; tuberculosis, polio, dengue and a host of other communicable diseases. Our efforts to combat these diseases have had varying degrees of success. Funding research into isolating causes, improving diagnostics, finding efficient treatment plans, and exploring methods of prevention have improved the situation somewhat, though this fight is far from over. But, with a strange and unanticipated connection to humanity’s ongoing battle with infectious maladies, an entirely new frontier of illnesses has opened up. A new class of diseases, under the collective title of autoimmune diseases, is rearing its ugly head. ‘Auto’, meaning self, and ‘immune’, pertaining to our immune system; these diseases pit our own bodies’ defenses against us. Think of this as the biology version of a scenario in which renegade soldiers might attack the very country that they formerly swore to protect.
Back in 2015, a meta-analysis of studies done in various countries estimated a nearly 12% global prevalence of autoimmune diseases. Calculating that against the global human population for that time, about 7.2 billion people, gives an estimated 864 million people suffering from these disorders. And yet, awareness of these diseases is startlingly low, with less than 13% of Americans being able to name an autoimmune disease. This is in spite of projections from NIH and other organisations, ranging from a conservative 23.5 million to nearly 50 million, for the number of US citizens suffering from such diseases. From an Indian perspective, population level data about autoimmune disorders as a whole is conspicuously scarce, masking the true extent of the problem. On top of all this, more than 80 different autoimmune diseases have been identified around the world so far. But, rather than causing diseases, isn’t the immune system supposed to protect us from them?
The immune system is composed of various types of cells and tissues, which are united in the effort to protect the human body against invasion. It is a complex system, that requires a high degree of cooperation and cross-talk between all its members in order to function properly. One way to think about the immune system is to consider that it uses two main strategies to do its job: innate and acquired. It has evolved multiple layers that work to prevent the entry of foreign substances (dubbed ‘antigens’) into our body and destroy the ones that manage to sneak past. Innate immunity, which is enforced by its components such as the skin, is present even before an infection occurs. The various facets of innate immunity recognize microbes and protect us from infection. Acquired immunity is that which adapts depending on the type of infection. While the biological basis of acquired immunity is also present beforehand, it matures as the infection occurs, producing powerful immune cells.
Understanding acquired immunity could be one of the keys to unlocking the autoimmune disease process. Acquired immunity consists of lymphocytes and their products, antibodies. One of the main facets of the acquired immune process is recognizing the foreign substances. This is done by the receptors present on the lymphocytes that are specific to these substances. Once they have been recognized, the lymphocytes activate a cascade of immune cells that eventually destroy the foreign intruders.
The question that now arises is how do lymphocytes identify whether a substance is foreign or not. The answer to that question is a concept called ‘immunological tolerance’. When immature lymphocytes are produced either in the bone marrow (B-lymphocytes) or in the thymus (T-lymphocytes), they undergo a series of checks to ensure they do not have any receptors for substances that are produced within the body. Any lymphocytes that do are deleted. This ensures that the lymphocytes do not attack the body’s own tissues and cause damage. But this mechanism fails sometimes, resulting in the production of lymphocytes that are auto (self) reactive and target self-antigens. Depending on where the self-antigen is present in the body, the immune reaction orchestrated by these rogue lymphocytes causes specific outcomes. If the antigen is present in a particular organ, then that organ gets damaged and malfunctions. For example, if the organ is the pancreas, then Type I Diabetes is the result. But, if the antigen molecule is present throughout the body, then the damage spreads over the whole body, like with diseases like Lupus.
But what makes autoimmune diseases such a difficult puzzle to solve? Firstly, autoimmune disorders seem to be develop from a mix of genetic and environmental factors. Genetic influences increase the incidence of disease in twins and people with relatives suffering from autoimmune diseases. In addition to a person’s genetic susceptibility, environmental triggers, such as infections, may also be involved. Some infections may serve as triggers for relapses in those already suffering from an autoimmune disease. But, and this is where things start getting strange, scientists have suggested that reduced exposure to certain microscopic organisms may have a role to play in the development of autoimmune disorders. An early version of this idea became the ‘hygiene hypothesis’, that seeks to find a correlation between the decrease in the rate of infectious disease and increase in autoimmune disease in developed nations. It is even being postulated that exposure to some infectious diseases may be protective against autoimmune diseases! A casual observer might give up at this point and declare that “All’s fair in love and immunology”. But, scientists are working hard to join the dots and solve this autoimmune puzzle.
A more recent set of ideas, known as the ‘Old Friends hypothesis’, is a more nuanced take on the same problem. During our evolutionary history, we would have been exposed to a huge range of microbes. Our immune systems may have become somewhat dependent on their presence to mature and function properly. But, in our quest to fight disease, we may be limiting our exposure to not just the dangerous microbes but the ‘friendly’ microbes as well. Broad-range and non-specific antimicrobial strategies like sterilization of food products, knee-jerk use of many antibiotics in humans and domesticated animals, and other measures associated with improved socio-economic conditions might end up having hidden costs.
Secondly, diagnosing autoimmune disorders is an uphill struggle. The clinical symptoms are extremely varied depending on the severity of these diseases, and different autoimmune diseases show significant clinical overlaps adding more missing pieces from different puzzles. Most autoimmune disorders also display complicated clinical courses with relapses and remissions, frequently with a lack of an easily identifiable trigger.
Thirdly, due to a combination of the above factors, autoimmune diseases are generally treated with immuno-suppressive drugs that operate at various levels of the immune system. Along with alleviating the symptoms, this sort of treatment increases the patient’s risk of developing opportunistic infections. Combining this with a global increase in autoimmune disease incidence by nearly 20% every year over the last 30 years shows us that autoimmune diseases form a new age epidemic that has to be tackled swiftly.
What is the way forward? Tackling such a mammoth issue must use a multi-pronged approach. Autoimmune research that focuses on identifying specific causative genes will lead to a better understanding of what drives the human autoimmune process. It will also help create targeted gene therapies with minimum side effects. The latter is significant as most autoimmune diseases are chronic and the toxicity of the medication can sometimes outweigh the benefits. Exploring combination drug therapies that specifically target various groups of immune cells can effectively enhance treatment efficacy without increasing associated side effects.
Building awareness plays a crucial role in early disease diagnosis. Organizations such as the American Autoimmune Related Diseases Association (AARDA) and European Network On Rare Primary Immunodeficiency, Autoinflammatory And Autoimmune Diseases (ERN RITA) are working to educate people on the risk factors, types and prevalence of autoimmune diseases. To focus public attention in USA, AARDA has designated March as ‘National Autoimmune Disease Awareness Month. Celebrities such as Seal, Nick Cannon and most recently, Selena Gomez have been vocal about their struggles with Lupus which has led to greater interest in the disease. Their stories are reassuring to patients of autoimmune disease, showing that it is possible to live, thrive and hope for a better future for themselves and their loved ones. These celebrity accounts, as well as those of other patients highlight the importance of a strong support system of friends and family in battling chronic illness. Raising awareness about these diseases will also help to lessen the fear, uncertainty and stigma that people might feel in dealing with an otherwise unknown illness.
With a disease burden that rivals that of cancer and heart disease combined, autoimmune disease has caused the scientific and medical communities to sit up and take notice. While research ticks on, trying to unravel the mysteries of autoimmunity, it is our collective responsibility to mobilise public attention on this problem and rally support for people suffering from these diseases.
Kaushik Eswaran is currently doing his internship at Jawaharlal Nehru Medical College, Belagavi in Karnataka having finished his MBBS from the same college
Very nice articulation Kaushik Congrats