Chapter 18 Autoimmune disease

The immune system is closely regulated to minimize the risk of self-antigens being recognized as foreign, leading to immune-mediated damage to an individual’s own cells and tissues. This regulation occurs by mechanisms that induce immune tolerance (Fig. 3.18.1). Suppressor CD8 T cells can also inhibit the immune response, in part by releasing inhibitory cytokines (e.g. IL-10). Autoimmune diseases develop when one or more of these protective mechanisms fails or is bypassed.

Mechanisms of autoimmune disease development

The role of immunogenetics

Correct functioning of the immune system is reliant upon complex interactions between immunoreactive cells and their targets. These interactions involve molecules present on the surfaces of cells, many of which are transmembrane in nature and, therefore, may also interact with intracytoplasmic components. Many of the genes encoding molecules such as the HLA family and cytokines (or their promoter regions) are highly polymorphic (meaning that one or more variants of the genes exist) and these polymorphisms may alter the detailed structure of the molecules (e.g. the antigen-binding groove of HLA molecules) or possibly the level of expression of molecules (e.g. cytokines). These changes can modulate immune responses, leading to interindividual differences in the response to antigens and the risk of development of forms of aberrant immune response such as those characterizing autoimmune disease. Individuals possessing certain HLA genetic polymorphisms are at increased risk of developing particular autoimmune diseases (Table 3.18.1).

Table 3.18.1 Associations between HLA alleles and autoimmune diseases

Disease Associated HLA locus/allele Relative riska
Coeliac disease DQ2 250
Ankylosing spondylitis B27 > 150
Reactive disease B27 > 40
Type 1 diabetes mellitusb DQ8 14
  DQ6 0.02
Multiple sclerosis DR2, DQ6 12
Rheumatoid arthritis DR4 9
Haemochromatosis A3 6
Addison’s disease DR3 5
Graves’ disease DR3 4
Myasthenia gravis DR3 2

a Relative risk measures frequently of the disease in question in individuals with an HLA locus allele compared with those not carrying the allele.

b Complex HLA associations occur.

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Jul 3, 2016 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on disease

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