Discussion: Causative Agent and Host Response (Part One)

The subjects of papers in this conference session concerned recovery of the Lyme disease spirochete from patients, antibody responses and immunodiagnostic tests for Lyme disease, and immunochemical studies of Lyme disease spirochetes. During discussion, several general topics were addressed: (1) methods for detection of spirochetal antigens in synovial tissues, (2) evidence that antigens other than those on the outer spirochetal membranes are immunogenic, (3) measurement of the onset and duration of specific antibody responses in Lyme disease. In regard to the first topic, it was pointed out that previous studies utilizing synovial culture techniques for detecting the presence of spirochetes have not been successful so far. The use of immunochemical stains for direct visualization seems promising. Monoclonal antibody preparations or techniques that employ DNA hybridization methods for detection of specific DNA may be useful for antigen detection at various stages of the disease. Demonstration of spirochetal antigen in immune complexes has not yet been successful. In regard to isolation of spirochetes from the blood of Lyme disease patients, it was pointed out that, as is the case with leptospires in leptospirosis infections, isolation of the agent may be possible only during the first few days of clinical illness, prior to development of specific antibody. Spirochetal isolation from Lyme disease skin lesions has been possible in specimens obtained from the papillary dermis. Discussion continued concerning the presence and activity of immunogens in Lyme disease other than those present on the outer spirochetal membrane; antibody binding to flagella has now been demonstrated. It was also mentioned that proteoglycan may be a poorly degradable and persistent material which might be involved in immunopathologic mechanisms having a role in prolongation of clinical disease. In this regard preliminary results utilizing both immunofluorescence and Western blot techniques indicate that Lyme disease patients do develop antibodies to proteoglycan; patients with secondary syphilis have similar responses, suggesting the presence of cross-reactive antigens in the two diseases. The usefulness of specific antibody responses for differentiation of Lyme disease from other forms of arthritis was reviewed. It was emphasized that the presence of antibody correlates closely with the clinical stage of Lyme disease. Specific spirochetal IgM responses measured by immunofluorescent techniques may be delayed early in disease but are demonstrable in 50 percent of patients with erythema chronicum migrans. In one series, 94 percent of Lyme disease patients had elevated IgG responses several weeks after onset of symptoms, and all patients having active arthritis were antibody-positive. Elevated IgG titers have also been demonstrated in patients with inactive Lyme disease, but the clinical significance of this observation is not understood. One Lyme disease patient was described who has now been in clinical remission for four years but continues to maintain elevated IgG antibody levels. Both immunofluorescence and ELISA techniques were found to be sensitive methods for determination of the presence of specific spirochetal antibody.