Development of autoimmunity in Lyme arthritis.
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.
Guerau-de-Arellano
Mireia
M
Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Huber
Brigitte T
BT
D000954:Antigens, Surface / Q000276:immunology; D001170:Arthritis, Infectious / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D004352:Drug Resistance, Microbial; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008074:Lipoproteins; D008193:Lyme Disease / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D008954:Models, Biological; D018716:Molecular Mimicry
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D008074:Lipoproteins; C072045:OspA protein