Autoimmune mechanisms in antibiotic treatment-resistant Lyme arthritis

In about 10% of patients with Lyme arthritis in the United States, joint in flammation persists for months or even several years after the apparent era dication of the spirochete, Borrelia burgdorferi, from the joint with antib iotic treatment. We propose a model of molecular mimicry affecting genetica lly susceptible individuals to explain this treatment-resistant course. The majority of patients with treatment-resistant Lyme arthritis have HLA-DRB1 *0401 or related alleles, and the severity and duration of their arthritis correlate with cellular and humoral immune responses to outer-surface prote in A OspA) of the spirochete. Using an algorithm, the immunodominant epitop e of OspA presented by the DRB1*0401 molecule was predicted to be located a t aa 165-173. Ln a search of the Genetics Computer Group gene bank, only on e human protein was identified, lymphocyte function associated antigen-1 (h LFA-1), that had sequence homology with OspA(165-173) and predicted binding in the DRB1*0401 molecule. Synovial fluid T cells from most patients with treatment-resistant arthritis responded to both OspA and hLFA-1, whereas th ose from patients with other forms of chronic inflammatory arthritis did no t. Molecular mimicry between a dominant T cell epitope of OspA and hLFA-1 m ay be an important factor in the persistence of joint inflammation in genet ically susceptible patients with treatment-resistant Lyme arthritis. (C) 20 01 Academic Press.