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 (OspA(165-173)). The human Lymphocyte Function Antigen-1 (hLFA1 alpha) contains a peptide with homology to OspA(165-173). Treatment-resistant Lyme arthritis patients' T cells, cloned based on their ability to bind OspA(165)-(173)-loaded HLA-DRB1 *0401 tetramers, respond to OspA and hLFA1 a with a different cytokine profile, suggesting that hLFA1 a acts as a partial agonist with a potential role in the perpetuation of joint inflammation. (C) 2002 Lippincott Williams Wilkins, Inc.