from medline:
1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11130454&dopt=AbstractRose NR, Mackay IR.
Molecular mimicry: a critical look at exemplary instances in human diseases.
Cell Mol Life Sci. 2000 Apr;57(4):542-51. Review.
PMID: 11130454
"…Based on analogous sequences of amino acids or on cross-reactions of monoclonal antibodies, numerous examples of such mimicry have been reported. There are, however,
no clear examples of a human disease caused by molecular mimicry."
2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11818475&dopt=AbstractKeegan BM, Noseworthy JH.
Multiple sclerosis.
Annu Rev Med. 2002;53:285-302.
PMID: 11818475
http://med.annualreviews.org/cgi/content/full/53/1/285#S2from abstract:
"…
The etiology [of multiple sclerosis] is unknown…;
from text:
Infectious Agents The list of infectious agents reportedly associated with MS, either serologically or pathologically, is extensive (41),
but none of the associations are conclusive, and separate laboratories have not always replicated earlier preliminary results. Infectious agents are known to cause demyelinating diseases in animals [e.g., visna, Theiler's murine encephalomyelitis virus (TMEV)], as well as in humans (e.g., JC virus causes progressive multifocal leukoencephalopathy). Exposure to an infectious agent in a genetically susceptible individual or within a critical time in development is proposed to cause MS, with acute attacks possibly relating to reactivation of a latent infection. Genetic determinants of susceptibility and severity of disease are evident in TMEV (42). Exposure to foreign agents that are antigenically similar to normal tissue may lead to autoimmune attack against self-antigens [i.e., molecular mimicry (43)]. Damage to normal tissue may expose novel antigens to the immune system that would otherwise not be contacted and further direct attack against nearby self-antigens (i.e., epitope spreading).
Infectious agents undergoing current investigation as to their relationship to MS include Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and Chlamydia pneumoniae (44). EBV is a lymphotropic herpes virus. Prior exposure to EBV as determined by seropositivity for IgG antibodies is reported in close to 100% of MS patients, compared with only 90% IgG and 4% IgM of seropositivity in normal controls (45). Investigators argue that prior exposure to EBV is necessary, although obviously not sufficient, for the development of MS. Reactivation as evidenced by EBV DNA within blood appeared to correspond to acute relapses of MS in one report (45).
HHV-6 is a beta–herpes virus that is both lymphotropic and neurotropic. Some investigators have found HHV-6 DNA directly within actively demyelinating plaques (46). HHV-6 DNA and high levels of IgM antibodies to HHV-6 antigen are found serologically in RRMS (47). Other investigators, however, have not found a similar association between HHV-6 and MS (48).
Chlamydia pneumoniae, a gram-negative intracellular organism, is a common respiratory pathogen. In one study, investigators cultured C. pneumoniae from the CSF in 64% of MS patients but only 11% of controls (49). The investigators found evidence of C. pneumoniae protein within the CSF by polymerase chain reaction (PCR) assay and elevated immunoglobulins specific for C. pneumoniae antigens within the CSF. Again, these results have not invariably been confirmed by other laboratories (50).
It is unclear whether these ubiquitous organisms are pathogenic or are merely revealed because the patients have a damaged CNS and an ongoing autoimmune disease. More studies are needed, ideally with replication in different laboratories using standardized techniques, to identify the organisms and clearly delineate the mechanisms of these agents in the pathogenesis or maintenance of demyelinating disease. Currently, it is probably premature to test individual patients or initiate treatment aimed at eradicating suspected pathogenic organisms outside of an investigational setting
3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10615080&dopt=AbstractAlbert LJ, Inman RD.
Molecular mimicry and autoimmunity.
N Engl J Med. 1999 Dec 30;341(27):2068-74. Review. No abstract available.
PMID: 10615080
Full text is linked here (I don’t know if either of these links will work from all computers):
http://content.nejm.org/cgi/content/full/341/27/2068http://content.nejm.org/cgi/content/full/341/27/2068?ijkey=X2EZWMRQd9gtI"…In view of these considerations, the experimental and clinical evidence purported to establish a mechanism for molecular mimicry in the pathogenesis of autoimmune diseases needs to be examined critically, with the recognition of several important principles. First, antigenic mimicry alone may not be sufficient for pathologic tissue cross-reactivity (in the absence of adequate costimulation and necessary cytokines). Second, neither antigen homology nor T-cell proliferation in response to complexes of MHC molecules and peptides can alone be considered a specific indicator of pathogenic mimicry. Third, the demonstration of a tissue-specific antibody response is likewise not, in itself, a specific indicator of pathogenic mimicry and may be due to tissue injury. Finally, antigenic mimicry may elicit tolerance of the host immune response rather than autoimmunity.37 …."
"…In the spondyloarthropathies, particularly Reiter's syndrome and reactive arthritis, there is a clear temporal relation between arthritis and antecedent bacterial infection, combined with a strong host genetic susceptibility (HLA-B27). Early studies provided support for the concept of microbial mimicry of B27 based on monoclonal-antibody cross-reactivity13 and sequence homologies.14 A systematic search of a sequence data base showed that B27, to a greater degree than other B alleles, shares an unexpected number of hexapeptides and pentapeptides with gram-negative bacterial proteins.15
However, the pathogenic importance of this mimicry has not been established.. Numerous bacteria that have sequence homologies with B27 (e.g., Escherichia coli) do not appear on clinical grounds to be pathogens that cause arthritis, and T-cell reactivity against microbial peptides recognized by anti-B27 antibodies has not been established.16 In a study of B27-transgenic mice immunized with a shared peptide of B27 and klebsiella, the B27 genotype, instead of predisposing the mice to arthritis, actually rendered them tolerant to this shared peptide.17 This finding supports the idea that antigenic mimicry may induce tolerance rather than autoimmunity..."
"
CONCLUSION: The experimental and clinical models discussed above fall short of resolving the key issues in the demonstration of molecular mimicry as a pathogenic mechanism in autoimmune disease.Edited by Evelyn on 04/19/02 12:51 PM (server time).
Edited by Evelyn on 04/19/02 12:54 PM (server time).
Edited by Evelyn on 04/19/02 02:30 PM (server time).
