Autoimmunity , triggered by a breakdown in self-tolerance , can lead to a wide range of diseases that are increasing in prevalence and have major impact on individuals and society
Sascha Gerdes MD Department of Dermatology , University Medical Center Schleswig- Holstein , Campus Kiel , Germany
The primary function of the immune system is to protect the body from infectious agents including viruses and bacteria . The body ’ s own cells and molecules do not usually stimulate an immune response because of a variety of mechanisms that ensure self-tolerance . 1 However , in certain circumstances they do stimulate a response and the body ’ s own structures are attacked as if they were foreign , a condition called autoimmunity . 2
An autoimmune disease is any disease resulting from an abnormal immune response that attacks the body ’ s own cells and tissues , and more than 80 autoimmune diseases have been identified . 2 , 3 Some of the more common autoimmune diseases or immune-mediated diseases resembling autoimmune diseases include type 1 diabetes , rheumatoid arthritis ( RA ), systemic lupus erythematosus ( SLE ), inflammatory bowel disease ( IBD ), psoriasis , psoriatic arthritis , and ankylosing spondylitis . 4 – 6
The overall prevalence of autoimmunity is around 3 – 5 % of the general population . 1 , 3 The incidence and prevalence vary among the different autoimmune diseases and can vary between geographical regions . 1 Autoimmunity and autoimmune diseases are increasing dramatically in many parts of the world , likely as a result of changes in exposure to environmental factors . The prevalence of antinuclear antibodies – the most common biomarker of autoimmunity – has increased from 11 % to 16 % among the US population over 25 years . 7 Estimates put yearly increases in the worldwide incidence and prevalence of autoimmune diseases at 19 % and 12.5 %, respectively . 8
Autoimmune diseases can occur at any age , although specific diseases have their own characteristic age of onset . There is an increased frequency of autoimmune diseases in women with up to 9:1 female to male ratio as found in SLE 9 ( with the exception of Crohn ’ s disease with a ratio of 1:1.2 ). 1
General principles of autoimmune diseases The body ’ s defence against infection can arise from natural ( innate ) immunity resulting from the genetic constitution of the body , or it can be acquired as a result of an adaptive immune response stimulated by a foreign antigen . Adaptive immunity is based on properties of T cells and B cells ( lymphocytes ) that can respond selectively to thousands of different antigens , leading to specific memory and a permanently altered pattern of response . Adaptive functions mostly exert their effects through antigen-specific responses with helper T cells activating B cells , macrophages and cytotoxic T cells as well as B cell produced antibodies that activate other components of innate immunity . 10
Autoinflammatory and autoimmune diseases arise from abnormal changes in both innate and adaptive immunity . Consequently , autoinflammatory and autoimmune diseases share similar characteristics : activation against self , subsequent systemic inflammation , and the absence of a clearly identified external causal trigger . 11 The main difference between the two is that in autoinflammatory diseases , the innate immune system directly causes inflammation due to dysregulated secretion of pro-inflammatory cytokines and consequent damage to host tissues . Autoimmune diseases occur when native host cells are recognised as ‘ foreign ’ and the adaptive immune cells target these ‘ foreign ’ cells for destruction and activate the
Autoimmunity and autoimmune diseases are increasing dramatically in many parts of the world , likely as a result of changes in exposure to environmental factors inflammatory process . 12 In fact , many diseases lie on a spectrum from autoinflammatory to autoimmune with variable contributions of both the innate and adaptive immune responses to particular diseases . 11
The thymus and bone marrow play a key role in central immune tolerance to maintain homeostasis . In the thymus , developing T cells undergo positive selection before entering the circulation . Mature T cells are subject to secondary selection ( peripheral tolerance ) by which the majority of autoreactive T cells are deleted . 1
Even under strict control by central and peripheral tolerance mechanisms , a small number of autoreactive T and B cells can escape into the periphery in normal conditions . Here they will remain harmless unless there is a genetic predisposition to break tolerance and / or an environmental trigger that allows pathological autoimmunity to develop leading to tissue damage . 1
Monocytes and macrophages are innate immune cells that promote an immune-modulatory , proinflammatory , or repair response depending on the microenvironment . Several factors can influence the contribution of monocytes and macrophages to the development of autoimmune / autoinflammatory diseases , such as genetic predisposition , epigenetic changes , or infections . 13 Some vaccines and microorganisms can induce epigenetic changes in monocytes and macrophages modifying their functional responses . This process is known as trained immunity , in which the innate immune response is enhanced
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