REVIEW - Cell damage and autoimmunity: a critical appraisal

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J Autoimmun. 2008 Feb-Mar;30(1-2):5-11.

Cell damage and autoimmunity: A critical appraisal.

Mackay IR, Leskovsek NV, Rose NR.

Department of Biochemistry and Molecular Biology, Monash University,

Clayton, 3800, Australia.

In April 2007, an international Colloquium bridging scientific and clinical

disciplines was held to discuss the role of cellular and tissue damage in

the initiation, development and persistence of autoimmune disease. Five

potential etiologic and pathophysiologic processes fundamental to autoimmune

disease (i.e. inflammation, infection, apoptosis, environmental exposure and

genetics) were the focus of the presentations and integrative discussions at

the Colloquium. The information presented on these topics is condensed in

this review. Inflammation has close clinico-pathologic associations with

autoimmunity, but future analyses will require better definition and metrics

of inflammation, particularly for the earliest cellular and molecular

components dependent on recruitment of elements of innate immunity. Although

infection may be associated with increased levels of autoantibodies, most

infections and virtually all vaccinations in humans lack well-established

links to autoimmune diseases. Further application of well-designed,

long-term epidemiologic and population-based studies is urgently needed to

relate antecedent exposures with later occurring stigmata of autoimmunity

with a goal of discerning potentially susceptible individuals or

subpopulations. Suspect infections requiring closer interrogation include EB

virus (SLE and other diseases), HCV (autoimmune hepatitis), beta hemolytic

streptococci (rheumatic carditis) and Helicobacter pylori (autoimmune

gastritis) among others. And even if a micro-organism was to be

incriminated, mechanisms of initiation/perpetuation of autoimmunity continue

to challenge investigators. Plausible mechanisms include potentiation and

diversion of innate immunity; exposure or spillage of intracellular

autoantigens; or provision of autoantigenic mimics. Integrity of apoptosis

as a critical safeguard against autoimmunity was discussed in the contexts

of over-reactivity causing autoantigens to gain enhanced exposure to the

immune system, or under-reactivity producing insufficient elimination of

autoreactive clones of lymphocytes. Although environmental agents are widely

believed to serve as necessary " triggers " of autoimmune disease in

genetically predisposed individuals, only a few such agents (mainly drugs

and some nutrients) have been clearly identified and their mechanism of

action defined. Finally an essential genetic foundation underlies all these

hazards for autoimmunity in the form of risk-associated polymorphisms in

immunoregulatory genes. They may be predictive of future or impending

disease.

PMID: 18194728

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve & db=PubMed & list_uids=18

194728 & dopt=AbstractPlus

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