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Chapter 12 : Autoimmunity in Lyme Arthritis: Molecular Mimicry between OspA and LFA-1

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Abstract:

The first indication that autoimmunity might play a role in treatment-resistant Lyme arthritis was a study of HLA-allele association with Lyme arthritis. The risk for development of treatment-resistant Lyme arthritis has been shown to double when patients have the HLA-DR4 specificity and generate an anti-outer surface protein A (OspA) antibody response. Immunodeficient severe combined immunodeficient (SCID) mice infected with develop severe arthritis, carditis, and hepatitis, which are preventable if anti-OspA antibodies are administered prior to infection and which are treatable if antibodies are administered after induction of arthritis. The authors' work has explored the population of active cells involved in the propagation of treatment-resistant Lyme arthritis. It had been previously shown that Th1 cells dominate the immune response in the synovial fluid of patients with Lyme arthritis, as well as those with RA or other types of chronic inflammatory arthritis. T-cell lines from patients with treatment-resistant Lyme arthritis have previously been shown to preferentially recognize OspA in comparison with T-cell lines from patients with treatment-responsive disease. The authors suggest that OspA, in the context of DR4-homologous alleles, triggers development of an autoimmune response to human lymphocyte function-associated antigen 1 (hLFA-1), which leads to treatment-resistant Lyme arthritis. That is, if the spirochetal infection is prevented from disseminating into the joint or is eradicated before a strong proinflammatory response can develop in the localized space of the synovial fluid, the vicious cycle of chronic inflammation is prevented before molecular mimicry and autoimmunity can develop.

Citation: Gross D, Huber B. 2000. Autoimmunity in Lyme Arthritis: Molecular Mimicry between OspA and LFA-1, p 161-173. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch12

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Figure 1

Model of how autoimmunity develops in patients with treatment-resistant Lyme arthritis. migrates to the joint and induces a localized Th1-dominant response with OspA specificity. The unbalanced production of IFN-γ induces upregulation of MHC class II on both classical and atypical APCs. Furthermore, LFA-1 expression becomes enhanced on T cells, as well as macrophages, as does ICAM-1 expression due to the presence of IFN-γ and itself. This results in processing and presentation of LFA-1, which leads to activation of OspA-primed T cells, even in the absence of .

Citation: Gross D, Huber B. 2000. Autoimmunity in Lyme Arthritis: Molecular Mimicry between OspA and LFA-1, p 161-173. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch12
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Tables

Generic image for table
Table 1

DR molecules with peptide-binding cleft residues homologous to DRB1*0401

Citation: Gross D, Huber B. 2000. Autoimmunity in Lyme Arthritis: Molecular Mimicry between OspA and LFA-1, p 161-173. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch12
Generic image for table
Table 2

OspA and hLFA-1α are not predicted to bind to DRB1*0402

Citation: Gross D, Huber B. 2000. Autoimmunity in Lyme Arthritis: Molecular Mimicry between OspA and LFA-1, p 161-173. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch12

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