The concept of "autoimmune disease" brings together a set of pathologies characterized by an inappropriate reaction of the immune system vis-à-vis the self's constituents. Their prevalence is very variable from one pathology to another but taken together. They concern around 10% of industrialized countries' population; this figure has been steadily increasing over the past decades.
The significant progress made in the diagnostic and therapeutic management of autoimmune diseases has allowed a spectacular lengthening of the life expectancy of patients, leading to the emergence of new problems: in addition to the control of the activity of the disease, the prevention of damage to noble organs, the improvement of the quality of life, the maintenance of professional integration, and the management of co-morbidities have now become central issues.
The immune system has a function of recognizing the exogenous and endogenous environment. B and T lymphocytes are programmed to recognize antigens by specific receptors (BCR for B lymphocytes, TCR for T lymphocytes). Given the extreme diversity of these antigen receptors' repertoire, the appearance of lymphocytes recognizing antigens of the self is statistically inevitable.
Tolerance mechanisms control these self-reactive cells, the latter being defined by the immune system's ability not to activate against self-antigens (self-antigens). Different mechanisms of tolerance allow the immune system to protect itself against autoreactive lymphocyte clones, eliminate them, or inactivate them.
Physiological autoimmunity is an important natural phenomenon that regulates the homeostasis of the immune system. It results from autoreactive B lymphocytes, which produce so-called “natural” antibodies (that is to say present in all individuals) of low affinity and T lymphocytes carrying autoreactive TCRs of low affinity.
Pathological autoimmunity is the result of a breakdown in immunological tolerance. This occurs during qualitative or quantitative changes in B- or T-reactive cells or autoantigens' activity and regulation. This breakdown in tolerance may be acquired or result from genetic abnormalities in the immune system's maturation.
Autoreactive cells can exert their pathogenic effects by different mechanisms: cytotoxicity of CD8 + T lymphocytes (exocytosis of cytotoxic molecules, induction of apoptosis of the target cell, etc.) and various mechanisms involving autoantibodies: cytotoxicity in the presence of complement (e.g., hemolytic anemia), deposits of immune complexes (e.g., lupus nephropathy), autoantibodies interfering with cell receptors (e.g., anti-acetylcholine receptor antibodies in myasthenia gravis). The abnormal secretion of cytokines, particularly pro-inflammatory such as interleukin 1, interleukin 6, or TNFα, also plays a crucial role in promoting inflammation and immune deregulation.
The presence of isolated autoimmune biology (for example, the isolated positivity of an anti-nuclear antibody test) without clinical manifestation or other biological manifestation is not sufficient to strictly define an autoimmune disease. However, in many cases, pathological autoimmunity appears before clinical signs appear, and medical monitoring is therefore recommended. Historically, autoimmune disease has been defined according to different criteria (Box 14.1). Main elements allowing to define an autoimmune disease
The immunological reaction of the immune system (autoantibodies, autoreactive cells) vis-à-vis a tissue or organ of the self.
Demonstration of these autoreactive effectors' pathogenic power in vitro or in vivo by transfer from one individual to another (in practice rarely demonstrated).
Reproduction of the disease by immunization against the target autoantigen.
Prevention and control of disease by the administration of immunosuppressive therapy.
Researchers like Paul E. Love who pioneers immunology research and investigations at the National Institute of Health (NIH) are the flagbearer of progress with respect to the treatment of autoimmune diseases.
His primary research focuses on the role and function of the immune receptor-tyrosine based activation motives (ITAMs), one of the groups of lymphocytes required for the clearance of infectious pathogens and tumour monitoring in the TCR - the leading activation receiver via T cells.