The Role of Autoimmune Reactivity
The results of recent studies conducted by NIAID and intramural scientists from the National Institute of Neurological Disorders and Stroke (NINDS) indicate that T cells from patients with chronic Lyme disease are reactive not only against B. burgdorferi-specific antigens but also against various host (self) antigens (Nature Medicine 5: 1375, 1999). Such antigenic mimicry might generate autoimmune inflammatory reactions that could be responsible for arthritic as well as some neurological symptoms associated with chronic Lyme disease. Intramural and extramural scientists are exploring the implications of this finding.
Antibodies against the OspA epitopes of B. burgdorferi also have been shown to cross react with neural tissue (J. Peripheral NervousSystem 9, 165, 2004; J Neuroimmunol 159, 192, 2005) as well as myocin (J Clin Microbiol 43, 850, 2005). Such antigenic mimicry may have the potential to generate autoimmune inflammatory reactions that could be responsible for the neurological symptoms associated with chronic Lyme disease. Intramural and extramural scientists are evaluating this possibility in greater detail. In this context, it is interesting to note that homologies between proteins of B. burgdorferi and thyroid antigens also have been reported (Thyroid 14, 964, 2004).
In clinical studies conducted by NIAID-supported extramural scientists, case subject patients with post-treatment chronic Lyme disease (PTCLD) were compared to control subjects without such symptoms for the presence of several human leukocyte antigen (HLA) class II (DRB1 and DQB1) genetic markers, some of which are known to be associated with the expression of autoimmune reactivity. The results obtained did not support the involvement of an autoimmune mechanism in PTCLD (J Infect Dis :192, 1010, 2005) . However, since not all autoimmune diseases are associated with specific HLA haplotypes, these findings do not necessarily exclude that possibility. Definitive proof clearly would involve demonstrating the presence of significant levels of relevant autoimmune antibodies and/or autoreactive T cells in patients with PTCLD but not in treated control subjects without such symptoms. A greater frequency of DRB1*0401, which has been reported to be associated with antibiotic-treatment resistant arthritis (Science 281: 703, 1998) was noted in the case subject patients; although this finding appeared to be nominally significant (p < 0.05), its biological significance is ambiguous since none of the case subjects considered had symptoms of inflammatory arthritis.
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