TARGETS FOR AUTOANTIBODIES FROM SYNOVIAL LESIONS IN CHRONIC LYME ARTHRITIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. While the causative agent of Lyme disease is definitively known to be the tick-borne spirochete, Borrelia burgdorferi (Bb), the etiology of chronic joint inflammation that ensues in a subset of patients remains less well understood. Persistence of arthritis after apparent eradication of the spirochete suggests an autoimmune reaction downstream of the original bacterial infection. We have generated recombinant antibody probes from synovial lesions within affected arthritic joints in an attempt to recapitulate disease-relevant antigen binding specificities at the site of injury. Using this panel of intraarticular probes, as well as antibody fragments derived from patient peripheral blood, we have identified cytokeratin 10 (CK10), present in synovial microvascular endothelium, as a target ligand and a putative autoantigen in chronic, antibiotic treatment-resistant Lyme arthritis. Further, there is cross-reactivity between CK10 and a prominent Bb antigen, Outer Surface Protein A (OspA). Release of the self protein in the context of inflammation-induced tissue injury and the resulting in situ response to it could set in motion a feed-forward loop, which amplifies the inflammatory process, thereby rendering it chronic and self-perpetuating, even in the absence of the inciting pathogen.