Antibody-based techniques for detection of Lyme disease: a challenging issue

Serologic assays detecting antibodies to Borrelia burgdorferi are useful in the routine diagnosis of Lyme disease. Despite the presence of new and improved assays, current laboratory diagnosis still requires optimization. The variety of genospecies and their different geographic distributions are the reasons why standards and recommendations are not the same for all of the main geographic regions, ie, USA, Asia, and Europe. Moreover, the variety and variability of antigens represents a significant challenge in assay design. This is due to the various antigens among the genospecies responsible for Lyme borreliosis; the changing antigens presented during infection; and the variability of single antigens. This review article discusses the immunologic response in Lyme disease over time, and the advantages and disadvantages of existing serological tests. Two tier testing is also introduced. Antigens useful for diagnosis, the properties of individual antigens and their appearance in infection especially the antigens appearing during mammalian infection, so-called “in vivo” antigens are introduced. To determine antibodies confirming infection in the nervous system, the same restrictions with regard to interpretation of enzyme-linked immunosorbent assay results in serum apply to cerebrospinal fluid. Furthermore, concentrations of antibodies in the two compartments, ie, blood and cerebrospinal fluid, are variable depending on compartmentalization (anatomic sequestration) and immunologic phenomena at immunologically privileged sites, such as the intrathecal space. To confirm neuroborreliosis, synthesis of antibodies in cerebrospinal fluid, should be measured in the form of a so-called antibody index. Further studies should focus on detecting the lowest concentration of antibodies and looking for useful new antigens, and the relationship between composition of such antigens and the patient’s clinical status.