In summary, the findings suggest that (1) the currently recommended CDC criteria for positivity in IgM and IgG western blot assays [5, 6] may need to be optimized, and (2) a PCR-based test such as the LM-PCR assay described here, applied to blood and urine samples, can be an important and perhaps necessary supplement to the presently recommended two-tier serological tests [5, 6] for more effective laboratory diagnosis of patients with Lyme disease. This evidence concerns the gene CD40LG and Lyme disease.