HPE Autoimmune disease: The fundamentals | 页面 8

TABLE 1

The course of autoimmune diseases

Predisposing factors Triggers and response Preclinical phase Overt disease

disease will not occur without an environmental trigger . ^{2 , 9}

Environmental factors – such as infectious agents , smoking , diet , the microbiome , and tissue injury – may initiate or augment the activation of autoreactive T cells that have escaped control and are poised to react against selfconstituents . ¹⁶ Tregs usually function to supress autoreactive T cells , but defects in development , stability or function may render these cells dysfunctional . In combination , these factors can contribute to activation and proliferation of autoreactive T cells and ultimately result in clinical disease ( Table 1 ). ²²

Environmental risk factors and triggers Environmental factors implicated in the development of autoimmunity include nutrition , the microbiota , infectious processes and xenobiotics , such as tobacco smoke , pharmaceutical agents , ultraviolet light , silica solvents , heavy metals , vaccines and collagen / silicone implants . ¹ However , there are very few environmental agents that clearly have a role in autoimmunity and identification of generic risk factors remains elusive .

Numerous infectious agents have been suggested to play a role in autoimmune disease , including bacteria , viruses , parasites and fungi . Infectious agents may contain antigenic determinants that resemble host epitopes – molecular mimicry – and are capable of eliciting an autoimmune response . ¹

The relationship between microbiota , host immune responses and autoimmunity is the subject of research interest , for example , changes in the gut microbiome are seen to precede onset of type 1 diabetes and are associated with disease progression . ¹ Alteration of the composition of the gut microbiome – reduction in microbial diversity , loss of beneficial bacteria , and a rise in symbiotic bacteria that become pathogenic under certain conditions – can trigger autoimmunity by mimicking self-antigens and may contribute to immune dysfunction through overactivation of the innate and adaptive immune systems . ⁹

Environmental factors are found to induce changes in apoptosis – programmed cell death . ¹ Autoantigens are seen within apoptotic cells and are responsible for antigen presentation , activation of innate immunity and regulation of macrophage cytokine secretion . Exposure to ultraviolet light can cause oxidative damage and induce apoptotic cell death . Ultraviolet light upregulates secretion of proinflammatory cytokines and chemokines important for recruiting immune cells to areas of inflammation . ²³

Smoking is associated with an increased risk of autoimmune disease that may take many years of long-term exposure to manifest , but moderate consumption is sufficient to affect disease risk . ^{17 , 23} Cigarette smoke contains several compounds that can elicit an innate immune response , and smoking is implicated in many autoimmune diseases , including RA and SLE . ¹ Similarly , other airway irritants encountered due to occupational hazards – such as silica and inorganic dust exposure – are associated with increased risk of RA . ¹⁷

Nutritional deficiencies can alter the immune response . Vitamin D is a natural immune modulator and reduced levels of vitamin D leading to an increased risk for loss of tolerance is implicated in multiple autoimmune diseases . ^{1 , 23}

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