Abstract
Treatment-resistant Lyme arthritis is associated with immune reactivity to outer surface protein A (OspA) of Borrelia burgdorferi, the agent of Lyme disease, and the major histocompatibility complex class II allele DRB1*0401. The immunodominant epitope of OspA for T helper cells was identified. A homology search revealed a peptide from human leukocyte function-associated antigen-1 (hLFA-1) as a candidate autoantigen. Individuals with treatment-resistant Lyme arthritis, but not other forms of arthritis, generated responses to OspA, hLFA-1, and their highly related peptide epitopes. Identification of the initiating bacterial antigen and a cross-reactive autoantigen may provide a model for development of autoimmune disease.
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.
MeSH terms
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Adolescent
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Adult
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Algorithms
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Amino Acid Sequence
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Animals
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Antigen Presentation
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Antigens, Surface / immunology
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Antigens, Surface / metabolism
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Arthritis, Reactive / drug therapy
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Arthritis, Reactive / immunology*
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Autoantigens / immunology*
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Autoimmune Diseases / immunology*
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Bacterial Outer Membrane Proteins / immunology
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Bacterial Outer Membrane Proteins / metabolism
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Bacterial Vaccines
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Borrelia burgdorferi Group / immunology
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Child
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Cross Reactions
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Female
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HLA-DR Antigens / genetics
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HLA-DR Antigens / immunology
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HLA-DR Antigens / metabolism
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HLA-DRB1 Chains
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Humans
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Immunodominant Epitopes
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Lipoproteins*
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Lyme Disease / drug therapy
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Lyme Disease / immunology*
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Lymphocyte Function-Associated Antigen-1 / chemistry
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Lymphocyte Function-Associated Antigen-1 / immunology*
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Lymphocyte Function-Associated Antigen-1 / metabolism
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Male
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Synovial Fluid / immunology
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T-Lymphocytes, Helper-Inducer / immunology
Substances
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Antigens, Surface
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Autoantigens
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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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Immunodominant Epitopes
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Lipoproteins
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Lymphocyte Function-Associated Antigen-1
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OspA protein