Exploring the dynamics of Borrelia burgdorferi sensu lato antibodies—a registry-based study on laboratory data from Sweden and Denmark

Objectives: Lyme borreliosis (LB) is the most common tick-transmitted infection in the northern hemisphere and is caused by bacteria in the Borrelia burgdorferi sensu lato (Bbsl)-complex. The diagnosis is partially based on serology, and clinicians often take follow-up serum samples to look for seroconversion or an increase in IgG-antibody levels. In this registry-based study, we proposed a method for determining actual changes in IgG and examined antibody reactivity and decay. Methods: Serological data from the departments of clinical microbiology at Karlstad Hospital, Sweden, and Slagelse Hospital, Denmark, were used to calculate a seroreactivity cut-off (SCOFF), above which changes between two samples from the patient cannot be explained by random variation. Increases in IgG reactivity as well as IgG and IgM decay were illustrated using time-to-event analysis and the SCOFF. Results: A total of 44,861 serum samples from 34,157 patients were tested for Bbsl-antibodies. Of the 4301 patients with follow-up samples taken within 100 days, 201 (4.67%) were above the SCOFF of 1.42 with a median time to follow-up sample of 36 days (interquartile range: 21). IgG demonstrated longer median time for all antibody levels (indeterminate: 4.6 years, low: 7.0 years, moderate-high: 8.8 years) than IgM antibodies (indeterminate: 2.1 years, low: 3.9 years, moderate-high: 6.8 years) and higher initial antibody levels persisted significantly longer for both IgG and IgM antibodies (p < 0.001). Of the 7868 patients with follow-up samples, isolated IgM reactivity preceded an increase in IgG reactivity in 18 patients (0.23%). Discussion: The SCOFF indicated little biological and random variation for Bbsl-specific IgG antibodies on the platforms used during the study. In most follow-up samples, both IgG and IgM antibodies persisted for years, with longer seropositivity associated with high initial antibody levels and IgG-type antibodies. The diagnostic value of isolated IgM reactivity was limited.