- Gross DM,
- Forsthuber T,
- Tary-Lehmann M,
- et al.
Purpose of the Study
In most individuals, the symptoms of Lyme arthritis resolve after the acute infection is eradicated. However, infection with Borrelia burgdorferi, the agent of Lyme disease, can sometimes trigger chronic arthritis that resembles an autoimmune disorder. This treatment-resistant Lyme arthritis is associated with immune reactivity to outer surface protein A (OspA) of B burgdorferi, and the major histocompatibility complex class II allele DRB1*0401. The purpose of this study was to try to define autoantigens that could be involved in the pathogenesis of chronic arthritis triggered by Lyme disease.
Individuals with treatment-resistant Lyme disease, and control subjects with other forms of chronic arthritis.
Methods and Results
The immunodominant epitope of OspA for T helper cells was identified. Examination of the bacterial protein sequence revealed homology to a human adhesion molecule, leukocyte function-associated antigen-1 (hLFA-1). Individuals with treatment-resistant Lyme arthritis, but not other forms of arthritis, generated responses to OspA, hLFA-1, and their highly-related peptide epitopes.
The authors conclude that identification of the initiating bacterial antigen and a cross-reactive autoantigen may provide a model for development of autoimmune disease.
The authors have made a convincing case of molecular mimicry as a cause of chronic Lyme arthritis. In this scenario, an immune response to the OspA bacterial protein triggers an immune response to LFA-1, a human protein with a similar structure. This work opens up new possibilities for the treatment of chronic arthritis after Lyme disease with peptides, or other immune modulators, that can block the interaction of autoreactive T cells with LFA-1.