It is a very common question that is asthma an autoimmune disease? Considering the fact that asthma has both the characteristics of autoimmune and non autoimmune disease. Here we discussed both the opinions in unbiased way. So that you will be able to make your own opinion knowing all the details.
What is asthma?
Asthma is a disease associated with breathing difficulty. Due to narrowing of the airway of the lung asthma arises. So there is airflow obstruction during breathing.
In asthma, less air passes through the narrow tubes and causes wheezing (a whistling sound). In asthma there is a special type of inflammation that makes people sensitive to various triggers. In asthma, mucus production also occurs that leads to coughing, breathing difficulty, etc.
What is Autoimmune disease?
Autoimmune disease is a disease where the body’s immune system attacks its own healthy cells and tissues. B cell receptors and T cell receptors of our body recognize body’s healthy tissue as antigen. So our immune system considers own body cell as foreign body and starts to act against it. Ultimately it causes a chronic inflammatory process and disrupts the normal function of the tissue.
Autoimmune disease affects 7 to 10 percent of persons in Europe and North America. The autoimmune disease causes disability and mortality.
Autoimmune disease reasons
Research suggests that genetic factors play an important role in the development of autoimmune diseases. Based on research, it is thought that autoimmune diseases occur due to genetic risk factor.
So genetic factor for autoimmune disease is shared for a range of diseases such as celiac disease, SLE, thyroiditis, Ankylosing spondylitis, type 1 diabetes and many more – all these are autoimmune disease by type.
For all these diseases, one thing is common: significant genetic regions are associated with autoimmune disease risk. Many of these genes encode proteins that are established therapeutic targets and have various biological effects.
A genome-wide association study conducted in 2010 identified a region on chromosome 17 that is strongly associated with susceptibility to asthma. Also, the region in chromosome 1 is associated with asthma in African ancestral children. Chromosome 1 contains a gene, DENND1B, that is expressed by natural killer cells which is a critical component of the immune system.
So various study results indicates that genetic role is an important key for development of various autoimmune diseases including asthma.
Is asthma an autoimmune disease- supportive reasons
- Occurrence of asthma more common in females, increased incidence of antinuclear antibody and detection of autoantibody against either bronchial epithelial antigen or endothelial antigen in patients with non-allergic asthma suggests that the disease may have an autoimmune connection.
- Approx. 50% percent of non-allergic asthma patients react to intradermal injection of autologous serum, pointing to circulating vasoactive factor’s presence and suggesting an autoreactive mechanism. Research shows that IgE reactive autoantigen has the potential to sensitize and induce immediate skin reactions along with airway inflammation.
- Asthma, a heterogeneous disorder characterized by chronic inflammation of the respiratory airways. The inflammation can be triggered by allergen exposure or can be due to other mechanisms, possibly autoreactive ( you may call it autoimmune also). Asthma is related to the autoimmunity concept is supported by its response to immunosuppressive drugs.
- Asthma and autoimmune disease have one-factor common-both of them are a result of the dysregulated immune system. A study of 2018 published in Allergy, Asthma and Immunology Research suggests that autoimmune mechanism in asthma is related to the disease severity.
- The key elements regulating the immune response both in asthma and autoimmune conditions are -mast cells, antibodies, T cells, cytokines and genetic determinants.
- The appearance of asthma and autoimmune diseases in the same patient may suggest that the immune system plays a key role in developing asthma and autoimmune disease in the same patient; that is, the mechanism for developing asthma and autoimmune diseases is the same.
- Mast cell that plays a significant role in asthma contains many inflammatory mediators. These inflammatory mediators have profound effects on many autoimmune processes. Inflammatory cytokines and environmental stress activate protein kinases that may lead to both allergic and autoimmune diseases.
- The presence of autoantibody indicates an autoimmune basis for asthma. These autoantibodies are present in autoimmune diseases also, suggesting autoimmunity in asthma. T cells play an important role in immune reactivity. T cell receptor loci are important for susceptibility to both asthma and autoimmunity.
- In the past various studies demonstrated that the ” possibility of a localized autoimmune phenomenon in an asthmatic lung with persistent eosinophils”, despite maintenance with oral steroid therapy.
- In 2012, a study by Wenzel et al. showed that patients with severe asthma who required oral steroids had asthmatic granulomatosis in the lung parenchyma. Researchers excluded autoantibody detection, but the steroid-sparing response to drugs such as azathioprine and methotrexate (these are typically given in autoimmune diseases) indicated a possible “autoimmune type anomaly”.
- In a recent study by Mukherjee et al. in 24 patients with eosinophilic asthma, anti eosinophil peroxidase (EPX) immunoglobulin G were reported in sputa, not in sera. The levels positively correlated with the sputum antinuclear antibodies.
- Researches found diverse immunofluorescence patterns, ranging from speckled to homogenous. Interestingly, only 4 out of 15 patients with severe asthma had circulating antinuclear antibodies. When all these are taken together, it indicates the presence of a polyclonal autoimmune event localized to the airways.
Autoimmune involvement of asthma, especially in adults with late-onset non-atopic asthma, has been studied. Pathogenic antibodies against EPX in patients with eosinophilic asthma with increased frequency of eosinophilic degranulation and EPX have been studied.
The research found that with the progression of disease and persistence of inflammation, the airways are constantly exposed to immunogenicity entities such as EPX and subsequent markers of tissue injury (DAMPs- danger associated molecular patterns), capable of triggering the adaptive immune response.
Autoimmunity and response to asthma therapy:
Research suggests that patients can respond differently to various therapies, and it can be affected by the presence of autoimmunity.
Such as, sometimes it is seen steroid subsentivity in severe asthma patients, here autoantibodies in the lung may be one mechanism that leads to steroid subsentivity in these patients.
The review authors mention that “One of the potential mechanisms may be attributed to the increase in autoantibody titles in eosinophil rich tissue, and then the consequent auto antibody-induced eosinophil degranulation with EETs (eosinophil extracellular traps).
Also, increased doses of corticosteroid can decrease the lymphocytic infiltration and eosinophil count in autoimmune tissue, but it is not efficient to decrease the number of autoantibodies or to suppress their immediate mechanism of action on the effector cell such as eosinophils.
Type2 inflammation and controversy:
In a most recent report by Global Initiative for Asthma(GINA), it is found that type 2 inflammation is present in approx.50 percent of patients with asthma and cytokines such as interleukin (IL)-4, IL-5, and IL-13 are present.
When our body recognizes allergens, then our adaptive immune system sometimes produces these cytokines. Viruses, bacteria and various other irritants that stimulate the innate immune system can activate type 2 inflammation through the production of IL33, IL-25 and thymic stromal lymphopoietin (TSLP) by epithelial cells.
Many research shows that autoimmune disease act through the type 1 or type 17 driven cell-mediated pathway; it is related with infection derived pathomechanism.
Still, other research reports show eosinophil (seen as a type 2 effector cell) has a role in many autoimmune diseases. Also, autoimmune diseases are increased in eosinophil mediated diseases ( such as eosinophilic esophagitis and hypereosinophilic syndrome).
It is observed that type 2 inflammation improves when patients with mild or moderate asthma regularly take inhaled corticosteroids. But in patients with severe asthma, it is found that type 2 inflammation may be “relatively refractory” ( means relatively unresponsive to treatment) to inhaled corticosteroids, even if given in high doses. Asthma patients may be responsive to oral corticosteroids but can give serious adverse effects, so the GINA report recommends the use of alternative treatments.
Novel biologics and immune responses:
Patients who have an exacerbation of poor symptom control, even if when they are taking high dose inhaled corticosteroids, long-acting beta-agonist (LABA) and patients who may have eosinophilic biomarkers or allergic biomarkers or patients who need maintenance with oral corticosteroids, the GINA report recommends using an add-on type 2 target biologic therapy.
GINA report also noted that if blood eosinophil levels were at least 260/microliter or fractional exhaled nitric oxide was at least 20 ppb, there is a decrease in asthma exacerbation as shown in randomized clinical trials. Other potential predictors of the good response included childhood-onset asthma and clinical history of allergen driven symptoms.
As per the Allergy, Asthma and Immunology Research Review research, it is found that immune pathways may be relevant in the use of biologics in the treatment of patients with severe asthma.
Such as, autoantibodies to IgE in asthma patients can interfere with omalizumab, giving a potentially compromising response.
Also, Patients with asthma who showed less than optimal response to mepolizumab had increased sputum IL-5 and anti-EPX IgE in their titers after treatment.
Also, it is found that reslizumab decreased autoantibody titers in the same group of patients with eosinophilic asthma, previously who were assessed for mepolizumab. Sputum anti -EPX IgGs was a predictor of response to anti-IL-5 monoclonal antibody therapy.
The presence of autoinflammation and autoantibodies and, subsequently, the development of autoimmunity is part of a spectrum of immunological diseases; in the same way, the innate and adaptive immune responses constitute the immunological continuum.
More research is needed in this regard, but the ongoing research already shows that the significance of autoimmunity and its relation with asthma severity and treatment response will evolve in the near future.
Is asthma an autoimmune disease- opposing opinion
There are several reasons for which asthma is not considered as an autoimmune disease to date. The reasons are the following
- Autoimmune disease occurs mostly in adulthood. Autoimmune disease in children is rare. But asthma in children are not that much uncommon.
- Autoimmune disease automatically comes and automatically goes away. There is no permanent or complete recovery in autoimmune disease. But in occupational asthma it is seen that complete recovery occurs if triggers are identified within 6 months of first appearance of symptoms.
- Autoimmune disease do not need a trigger for its occurrence. Autoimmune disease is the result of dysregulated immune system when our body detects own body cells as foreign object and build antibody against it. But in asthma, there is wide range of triggers such as dust mites, cat and dog fur, pollen, various chemicals, etc. These triggers causes development of asthma.
- There are various autoimmune diseases. It is seen if a person has a particular autoimmune disease, there is also chance of other autoimmune disorders in that same person. But people with asthma usually has no other autoimmune disease. People with asthma mostly do not complain about any immune dysfunction.
Asthma is a disease that can be controlled. It is to date is controversial whether asthma is an autoimmune disease or not. Various research suggests that asthma is an autoimmune disease, but there are also reports that indicate asthma is not an autoimmune disease.
Fact is, asthma has features of both types of diseases- autoimmune and non autoimmune! But you may consider it a non autoimmune disease that has auto immune property. That is why we discussed the topic, so that you know the facts and decide how you want to consider is asthma an autoimmune or not.
Be it autoimmune or not, the best part is that, it is more controllable than any other autoimmune diseases. So whether you consider it autoimmune or not, treat it in its early stage to get the best result. Stay healthy and happy.
- British Society for Immunology
- Centre for Applied Genomics
- Research Paper By Rottem M.a · Shoenfeld Y.b
- National Library of Medicine
- Research Paper Submitted By Lindsay Nicholson, University of Bristol, UK
- Harrison’s Principles of Internal Medicine 20th edition book (page 1957 to page 1969)
- Murray & Nadel’s Textbook of Respiratory Medicine 6th Edition book (page 1113 to page 1132)
- Davidson’s Principles and Practice of Medicine 23rd edition (page 589 to 595)