Clinical canine Borrelia burgdorferi (sensu lato) infections are associated with highly elevated total IgG ELISA titers and convalescent Th2 immune responses

Lyme disease is caused by <i>Borrelia burgdorferi</i> (<i>sensu lato</i>), which is transmitted through species belonging to the <i>Ixodes ricinus</i> complex. Canine Lyme Disease (CLD) is an established clinical entity in the USA. In Europe, an unambiguous diagnosis is rarely made, although it has been shown that dogs can be naturally infected and develop antibodies against <i>B. burgdorferi</i> (<i>s.l.</i>). The relation of <i>Borrelia</i> total IgG, IgG2, and IgG1 specific antibodies and the incidence of symptoms was studied in a prospective cohort study. In a tick-dense area in the Netherlands, 84 dogs in 4 age cohorts were followed up during 7 consecutive half-years. In addition, 31 Bernese Mountain dogs (BMD), known to have robust anti-<i>Borrelia</i> antibody responses, were clinically monitored and serologically examined. Generalized estimating equations (GEE) analysis on repeated half-year measurements of clinical and serological results showed a strong association between the clinical signs fever combined with lameness in time, which in turn was associated with transiently high total IgG titers and elevated IgG1 titers against <i>B. burgdorferi</i> (<i>sensu stricto</i>). In BMD, we observed seroconversions and persistence of specific high total IgG and IgG1 titers. Although the latter also developed a persistent reaction against the <i>B. burgdorferi</i> (<i>s.l.</i>) C6 peptide, their tissues tested negative for <i>B. burgdorferi</i> (<i>s.l.</i>) DNA. This study strongly suggests that dogs - not vaccinated against <i>Borrelia</i> spp. infections - that encounter yearly tick infestations are recurrently infected. Some breeds, such as Labrador Retrievers and BMD, in the course of multiple tick-infestation seasons, develop transient symptoms compatible with CLD. Symptoms were strongly associated with temporarily raised total IgG and concomitant or convalescent high IgG1 antibody responses against <i>B. burgdorferi</i> (<i>sensu stricto</i>). Our findings provide insights into the resistance of dogs against <i>B. burgdorferi</i> (<i>s.l.</i>) infections and show that transient symptoms of CLD only occur in a subset of infected dogs.