- Direct evidence from transfer of pathogenic antibody or pathogenic T cells.
- Indirect evidence based on reproduction of the autoimmune disease in experimental animals
- Circumstantial evidence from clinical clues
There so many suspected autoimmune diseases that do not fulfill all of the postulates. I personally have a major problem with the last criteria. Essentially, the last criteria bases diagnosis on pretty circumstantial clinical evidence. We can't convict someone based on circumstancial evidence, so why are we using circumstantial evidence from clinical clues to diagnose a disease as autoimmune? For example narcolepsy is a suspected autoimmune disease (See more in Mignot, E (2001). "A commentary on the neurobiology of the hypocretin/orexin system". Neuropsychopharmacology 25 (5 Suppl): S5–13) By constrast some are question whether Multiple Sclerosis is truly and autoimmune disease. Some people have argued that cancer, to some extent has some autoimmune qualities.
Autoimmune diseases can also be classified by hypersensitivity based on types II, III or IV. The reason I posted this blog was to reexamine how we as scientist see as autoimmunity, and whether autoimmunity can really be narrowed down because autoimmunity is so broad and can include so many things. For more on these criteria, check out a paper by Rose and Bona called Defining criteria for autoimmune diseases (Witebsky's postulates revisited). I know the paper is a bit old, but the link can be seen at http://www.ncbi.nlm.nih.gov/pubmed/8216719.
This post is very interesting and related to the post I recently added (Re-thinking multiple sclerosis). I wasn't aware of the criteria in defining a disease as autoimmune and I agree with you that Witebsky's postulates are overly ambiguous. I think this reflects our general lack of understanding of autoimmune disease and pathology. There are certain diseases which are clearly autoimmune, such as Graves' disease, SLE, and Goodpasture's syndrome. Even though the pathology of these diseases are well understood, I don't know whether or not is understood why the immune system becomes dysregulated in the first place. With these ambiguous criteria, I think it becomes easy to label a disease as "autoimmune" even if the evidence for autoimmunity is weak or misinterpreted. Multiple sclerosis has traditionally been labeled an autoimmune disease and for years, MS research focused on that fact. It is only relatively recently that this view has been challenged. I think because this traditional view is being challenged that real progress will be made in understanding MS.
ReplyDeleteGood discussion, Samiat and Jared! Yes, the Witebsky postulates are getting a bit tired; it was a brave attempt to make the approach more scientific, like Koch's Postulates for deciding a particular organism causes an infectious disease. As far as I know, only in one condition was the first rule demonstrated (Goodpasture's Syndrome) where the antibody was removed from a patient's kidneys and transferred to a chimp, which promptly got the same disease.
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