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. 2020 Sep 25;15(9):e0239453.
doi: 10.1371/journal.pone.0239453. eCollection 2020.

Cerebrospinal fluid oligoclonal bands in Neuroborreliosis are specific for Borrelia burgdorferi

Klaus Berek  1 , Harald Hegen  1 , Michael Auer  1 , Anne Zinganell  1 , Franziska Di Pauli  1 , Florian Deisenhammer  1
Affiliations

Cerebrospinal fluid oligoclonal bands in Neuroborreliosis are specific for Borrelia burgdorferi

Klaus Berek et al. PLoS One. .

Abstract

Background: Cerebrospinal fluid (CSF) oligoclonal bands (OCB) occur in chronic or post-acute phase of inflammatory diseases of the central nervous system.

Objective: To determine whether CSF OCB in patients with neuroborreliosis (NB) are specific for borrelia burgdorferi senso lato.

Methods: We performed isoelectric focusing followed by immunoblotting in CSF of 10 NB patients and 11 controls (7 patients with multiple sclerosis, 2 patients with neuromyelitis optica spectrum disease, 1 patient with dementia and 1 patient with monoclonal gammopathy). Immunoblotting was performed using an uncoated as well as a borrelia antigen pre-coated nitrocellulose membrane (NCM). OCB were counted by visual inspection and photometric analysis. OCB were compared between uncoated und pre-coated NCM both in the NB and control group. For validation purposes inter-assay precision was determined by calculating the coefficient of variation (CV).

Results: Borrelia-specific OCB were found in the CSF of 9 NB patients and in none of the control subjects resulting in a sensitivity of 90% and a specificity of 100%. Number of NB specific OCB were 11±7 bands by photometric analyses compared to 9±5 bands by visual inspection. Validation experiments revealed an inconsistent inter-assay precision between visual and photometric analyses (NB uncoated: visual 28% versus photometric 14%, control subject uncoated: visual 16% versus photometric 24%).

Conclusions: In CSF samples with positive OCB, Borrelia-specific bands were detected in almost all NB patients and in none of the control subjects. Inconsistent inter-assay precision may be explained by a poor comparability of visual and photometric approach.

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Conflict of interest statement

The authors have read the journal's policy and the authors of this manuscript have the following competing interests: KB has participated in meetings sponsored by and received travel funding from Roche. HH has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, Siemens, Teva, and received honoraria for acting as consultant for Teva and Biogen. MA received speaker honoraria and/or travel grants from Biogen, Merck, Novartis and Sanofi. AZ has participated in meetings sponsored by, received speaking honoraria or travel funding from Biogen, Merck, Sanofi-Genzyme and Teva. FDP has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations) or travel funding from Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme, Teva, Celgene and Roche. FD has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Almirall, Alexion, Biogen, Celgene, Genzyme-Sanofi, Merck, Novartis Pharma, Roche, and TEVA ratiopharm. His institution has received research grants from Biogen and Genzyme Sanofi. He is section editor of the MSARD Journal (Multiple Sclerosis and Related Disorders). There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1
Oligoclonal bands on (A) uncoated and (B) pre-coated nitrocellulose membrane. The control patient showed mirror bands in CSF and serum (type IV) on the uncoated NCM (Fig 1A, left), while no bands could be detected using the pre-coated NCM (Fig 1B, left). The neuroborreliosis patient had OCB in the CSF but not in serum on the uncoated NCM (Fig 1A, right), and the same pattern (type II) using the pre-coated NCM (Fig 1B, right). Framed areas were used for semi-quantitative determination of oligoclonal bands by ImageJ. Abbreviations: CSF: cerebrospinal fluid. NCM: nitrocellulose membrane. OCB: oligoclonal bands
See this image and copyright information in PMC

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