The spectrum of autoimmune diseases ranges from those that are organ specific ( e . g ., type 1 diabetes ), in which antibodies and T cells react to self-antigens localised in a specific tissue , to organ non-specific or systemic diseases characterised by reactivity against antigens spread throughout various tissues ( e . g ., RA , SLE ). 1
The term immune-mediated inflammatory disease ( IMID ) is used to encompass a range of clinically diverse conditions characterised by common inflammatory pathways triggered by dysregulation of the normal immune response leading to organ damage . 14 IMIDs can affect the outer skin surface ( e . g ., psoriasis ) or the inner body surfaces including gut ( IBD ) or joints ( RA , psoriatic arthritis , ankylosing spondylitis ). Recently , a molecular-based classification has been proposed to better address pathophysiological similarities across IMIDs that affect different organs . 15 The skin , as the outer barrier of the body , and inner barriers such as the gut and joints are particularly prone to IMIDs since they are required to maintain tissue homeostasis at sites exposed to microbial , chemical and mechanical challenges . These barriers are equipped with regulatory systems that control , suppress , and resolve inflammation through anti-inflammatory cytokines , lipid mediators , and immune regulatory cells . 15 This concept may allow targeting of different IMIDs through shared disease pathways . 15
Phases of autoimmunity All autoimmune diseases go through sequential phases of initiation , propagation and resolution . 16 In the initiation phase , patients are typically unaware of clinical symptoms ( preclinical ). The preclinical phase is characterised by an asymptomatic period of varying length in which the immune system is activated and the autoimmune process is started . A variety of autoimmune and inflammatory manifestations may develop appearing as non-specific signs and symptoms which
increase in the last months before a clinical diagnosis is made . 17
During the propagation phase , patients present with clinical disease characterised by self-perpetuating inflammation and tissue damage due to cytokine production , epitope spreading , and a disrupted balance of T effector / T regulatory cells ( Teff / Treg ). 16
Resolution may be achieved with the activation of inhibitory pathways ( cell-intrinsic ) and Treg mechanisms ( cell-extrinsic ) to limit effector responses and restore the Teff / Treg balance . All phases are associated with a failure of regulatory mechanisms with the resolution phase defined by a partial , and in most cases , short-term ability to restore the balance of effector and regulatory responses . 16 Consequently , patients in the resolution phase often suffer from relapsing and remitting disease .
General causes of autoimmunity Autoimmunity is initiated by a combination of genetic predisposition and environmental factors that lead to loss of self-tolerance . 1 , 2 In the preclinical phase of autoimmune disease , genetically susceptible individuals will transition to asymptomatic autoimmunity before development of clinical manifestations . Several environmental risk factors have been identified as triggers for this transition . These events likely act through overlapping biological pathways involving oxidative stress , loss of immune tolerance , autoantibody formation , complement activation and immune complex deposition , epigenetic modifications and upregulation of cytokine expression . 18
With the advent of genome-wide association studies , many genetic polymorphisms that may play a role in different autoimmune diseases have been identified . 19 , 20 Nonetheless , bridging the gap between knowledge of genetic associations and improved understanding of disease pathology and patient benefit remains a challenge . 21 Polymorphisms in various immune-related genes – including human leukocyte antigen , cytokines and receptors , and those involved in central tolerance – can result in defective regulation or a reduced threshold for activation of autoreactive T cells . 16 However , even if a genetic predisposition is present , the autoimmune
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