Utility of Borrelia-specific IgM and IgG antibody titer determinations during a 12-year period – results from a clinical laboratory in Northern Sweden

Abstract

Interpretation of serological findings in suspected Lyme borreliosis (LB) is challenging and IgM reactivities may have low predictive value. Therefore, if used indiscriminately, there is a risk for incorrect diagnosis of LB. To evaluate the usefulness of IgM titer determination, we performed a study of the prevalence of Borrelia-specific antibodies in serological samples from patients with suspected LB analyzed during the period 2010 - 2021 at the University Hospital of Umeå in Sweden. In total, 19,335 samples had been analyzed for the presence of IgG and IgM antibodies. Overall, there were higher percentages of IgM positive or borderline titers, 1,847 (9.6%) and 905 (4.7%), respectively, than IgG positive or borderline titers, 959 (5.0%) and 406 (2.1%), respectively. Peak number of samples were recorded 2012 - 2013, exceeding 1,800, whereas there were around 1,200 during 2020 - 2021. The peak number of positive IgG and/or positive IgM samples were observed during the period 2015 - 2017 with close to, or above 400, and concomitantly, the proportion of IgG positive samples increased markedly. For IgG positive samples, the increase followed a positive linear time trend (P< 0.001). Peak monthly numbers were observed during August, September, and October. This seasonal increase was significant for the IgG positive group (P< 0.05), but not for the IgM positive/IgG negative group. Repeated samples were obtained from 3,188 individuals and of the initial samples 2,817 were (88%) IgG negative and 2,315 (72%) were IgM negative and of these, 130 (4%) showed IgG seroconversion and 300 (9%) IgM seroconversion. Collectively, the data demonstrate that IgG and/or IgM positive samples represented a minority of all samples, even when repeated sampling had occurred, and IgM positive samples were much more common than IgG positive samples. Thus, the accuracy of the clinical suspicion was low and this will lead to a low predictive value of the analysis, in particular of IgM. These findings question the use of IgM titer determination as a routine analysis.