Abstract
Treatment-resistant Lyme arthritis (TRLA) develops in 10% of Lyme arthritis patients and is characterized by continuous joint inflammation that does not resolve with antibiotic therapy. TRLA is associated with HLA-DRB1*0401 and related alleles, as well as with an immune response to the Borrelia burgdorferi (Bb) outer surface protein A (OspA). The immunodominant epitope of OspA in the context of HLA-DRB1*0401 corresponds to amino acids 165-173 (OspA165-173). The human Lymphocyte Function Antigen-1 (hLFA1alpha) contains a peptide with homology to OspA165-173. Treatment-resistant Lyme arthritis patients' T cells, cloned based on their ability to bind OspA165-173-loaded HLA-DRB1*0401 tetramers, respond to OspA and hLFA1alpha with a different cytokine profile, suggesting that hLFA1alpha acts as a partial agonist with a potential role in the perpetuation of joint inflammation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Antigens, Surface / immunology
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Arthritis, Infectious / complications*
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Arthritis, Infectious / genetics
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Arthritis, Infectious / immunology*
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Autoimmunity / immunology*
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Bacterial Outer Membrane Proteins / immunology
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Bacterial Vaccines
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Borrelia burgdorferi Group / immunology
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Borrelia burgdorferi Group / isolation & purification
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Borrelia burgdorferi Group / pathogenicity
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Drug Resistance, Microbial
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HLA-DR Antigens / genetics
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HLA-DR Antigens / immunology
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HLA-DRB1 Chains
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Humans
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Lipoproteins*
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Lyme Disease / complications*
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Lyme Disease / genetics
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Lyme Disease / immunology*
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Models, Biological
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Molecular Mimicry
Substances
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Antigens, Surface
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Bacterial Outer Membrane Proteins
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Bacterial Vaccines
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HLA-DR Antigens
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HLA-DRB1 Chains
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HLA-DRB1*04:01 antigen
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Lipoproteins
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OspA protein