20/10/2023
tps://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(23)00479-2/fulltext
The story behind the study: Exploring the dynamics of Borrelia burgdorferi sensu lato antibodies – a registry-based study on laboratory data from Sweden and Denmark Marc Westerholt, Ram B. Dessau and Lukas Frans Ocias.
The initial idea of examining the dynamics of Borrelia burgdorferi sensu lato-antibodies by looking at consecutive patient samples was conceived around four years ago, toward the end of Lukas F. Ocias’ (LFO) time as a PhD-student at the State Serum Institute in Copenhagen, Denmark. LFO and Ram B. Dessau (RBD), his co-advisor at that time, sought to determine what change in IgG constitutes an actual increase in IgG on follow-up samples. However, after an initial stage of planning, we became occupied with other matters.
Fast forward three years. LFO and Marc Westerholt (MW) had never met, despite both working in Clinical Microbiology and residing in Copenhagen. It was only after they each relocated more than 600 km away from the bustling streets of Copenhagen to the tranquil forests of Värmland, orchestrated largely by their respective partners, that they crossed paths at the Department of Clinical Microbiology in Karlstad. The project then found its second wind and the objective expanded with additional inquiries of practical clinical importance that needed answers: “How often does one see an actual increase in IgG on follow up samples?”, “How often does isolated IgM reactivity precede an IgG increase?” and “How long do antibodies against Borrelia persist?”
Both LFO and MW were concerned about the possibilities of pursuing an academic career in a charming but research-distant town like Karlstad, in a new country without an established academic network, funding or university affiliations. These obstacles were partly overcome by collaborating with former colleagues RBD and Karen A. Krogfelt (KAK) from Denmark, securing local grants for ethical approval and juggling the project alongside their routine laboratory work and personal time.
The laboratory in Karlstad turned out to be the ideal setting for this project. Not only did LFO and MW get the chance to share their common interest in research, but the laboratory had been analysing patient samples using similar CLIA-instruments for more than a decade. This provided a unique opportunity to tackle the aforementioned clinical questions using extensive datasets and time-to-event analysis. The process was not straightforward, and a finished article rarely reflects the sweat, tears and failed attempts that went into it.
One of the primary initial challenges revolved around determining a cut-off which could distinguish increases in IgG due to random variation from those caused by actual exposure. RBD and colleagues had previously used relative change to assess reactivity in follow-up samples and it only seemed natural to expand on this idea [1]. By examining the antibody reactivity during the winter months, when tick exposure is presumed to be negligible, a seroreactivity cut-off (SCOFF) capable of separating noise from real change in antibody concentration could be found.
Another challenge was finding a method to visualize antibody decay. After numerous attempts, we settled on the idea of using Kaplan-Meier curves. One advantage of using this approach is that once patients reach seronegativity, they are censored and thus not included again should reexposure occur. However, patients with a re-exposure before achieving seronegativity cannot be accounted for and will remain seroreactive.
Our hope is that this study will spark further discussions on the uses of serological analyses in the diagnosis of Lyme borreliosis, especially regarding the interpretation and usefulness of follow-up samples and the clinical utility of IgM antibodies.
Reference
Dessau RB, Fryland L, Wilhelmsson P, Ekerfelt C, Nyman D, Forsberg P, et al. Study of a Cohort of 1,886 Persons To Determine Changes in Antibody Reactivity to Borrelia burgdorferi 3 Months after a Tick Bite. Clin Vaccine Immunol. 2015 Jul;22(7):823–7.
Lyme borreliosis (LB) is the most common tick-transmitted infection on 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...
