Classical Borrelia Serology Does Not Aid in the Diagnosis of Persistent Symptoms Attributed to Lyme Borreliosis: A Retrospective Cohort Study

Foekje F Stelma; Anneleen Berende; Hadewych Ter Hofstede; Hedwig D Vrijmoeth; Fidel Vos; Bart-Jan Kullberg

doi:10.3390/life13051134

Classical Borrelia Serology Does Not Aid in the Diagnosis of Persistent Symptoms Attributed to Lyme Borreliosis: A Retrospective Cohort Study

Life (Basel). 2023 May 6;13(5):1134. doi: 10.3390/life13051134.

Authors

Foekje F Stelma^{1

2}, Anneleen Berende^{2

3}, Hadewych Ter Hofstede^{2

3}, Hedwig D Vrijmoeth^{2

3}, Fidel Vos³, Bart-Jan Kullberg^{2

3}

Affiliations

¹ Department of Medical Microbiology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
² Radboud Center for Infectious Diseases, 6525 GA Nijmegen, The Netherlands.
³ Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

Abstract

Objective: The diagnosis of Lyme borreliosis is based on two-tier testing using an ELISA and Western blot. About 5-10% of patients report persistent symptoms of unknown etiology after treatment, resulting in substantial difficulties in further diagnostic workup. This paper presents a study aimed at determining whether serology can differentiate between patients with persistent symptoms attributed to Lyme and other patients with Lyme borreliosis.

Methods: A retrospective cohort study included 162 samples from four subgroups: patients with persistent symptoms of Lyme (PSL), early Lyme borreliosis with erythema migrans (EM), patients tested in a general practitioner setting (GP), and healthy controls (HC). ELISA, Western blots, and multiplex assays from different manufacturers were used to determine inter-test variations in PSL and to compare reactivity against Borrelia-specific antigens among the groups.

Results: In comparing the IgG and IgM reactivity by Western blot, IgG was more often positive in the PSL group than in the GP group. The individual antigen reactivity was similar between the PSL and EM or GP groups. Inter-test agreement among the manufacturers was variable, and agreement was higher for IgG testing compared to IgM.

Conclusions: Serological testing is unable to define the subgroup of patients with persistent symptoms attributed to Lyme borreliosis. Additionally, the current two-tier testing protocol shows a large variance among different manufacturers in these patients.

Keywords: Borrelia; Lyme borreliosis; OspA; OspC; PTLDS; Vlse; p41; serology.

Grants and funding

This project was performed as an addendum to the PLEASE study [37] at the Radboudumc, Nijmegen, the Netherlands. This research did not receive any other specific grants from funding agencies in the public, commercial, or not-for-profit sectors. The authors performed the research within their institutions of employment.