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. 2021 Jul;28(7):2383-2387.
doi: 10.1111/ene.14853. Epub 2021 May 5.

Borrelia burgdorferi sensu lato seroconversion after intravenous immunoglobulin treatment: A cohort study

Ilse M Lucke  1 , Amber Vrijlandt  2 , Johan Lim  1 , Anneke J van der Kooi  1 , Ivo N van Schaik  1   3 , Hans L Zaaijer  4 , Joppe W Hovius  2 , Filip Eftimov  1
Affiliations

Borrelia burgdorferi sensu lato seroconversion after intravenous immunoglobulin treatment: A cohort study

Ilse M Lucke et al. Eur J Neurol. 2021 Jul.

Abstract

Objective: Intravenous immunoglobulin (IVIg) consists of pooled donor immunoglobulins (IgG), possibly including anti-Borrelia burgdorferi (Bbsl) antibodies. Apparent IVIg-related Bbsl seroconversion could lead to incorrect diagnosis of Lyme borreliosis. This cohort study was designed to determine how often IVIg treatment leads to apparent Bbsl seroconversion and whether antibodies disappear post-treatment.

Methods: Sera from chronic inflammatory demyelinating polyneuropathy (CIDP) and myositis patients were analyzed, drawn pre-treatment and 6-12 weeks after the start of IVIg. In patients with apparent seroconversion, follow-up samples after treatment withdrawal were analyzed, if available. Patients treated with corticosteroids were included as controls. A two-tier protocol was used for serological testing consisting of the C6 Lyme ELISA (Oxford Immunotec) and confirmation by immunoglobulin M (IgM) and immunoglobulin G (IgG) immunoblot (Mikrogen® ).

Results: We included 61 patients: 51 patients were treated with IVIg and 10 with dexamethasone. Of the patients treated with IVIg, 42 had CIDP (82%) and were treated with Nanogam® (Sanquin Plasma Products). Nine patients had myositis (18%) and were treated with Privigen® (CSL Behring). Anti-Bbsl IgG seroprevalence pre-treatment was 3% (2/61). Apparent seroconversion during IVIg treatment occurred in 39% (20/51) of patients, all treated with Nanogam. Post-treatment seroreversion occurred in 92% (12/13) of patients with available follow-up samples; in 78% (7/9) seroreversion was observed within 3 months.

Conclusions: Transient presence of anti-Bbsl IgG antibodies after IVIg is regularly observed. This effect appears to be dependent on the IVIg brand, probably reflecting variation in Bbsl exposure of plasma donors. Lyme borreliosis serological testing during, and weeks to months after, IVIg is therefore of limited utility.

Keywords: Borrelia burgdorferi; CIDP; IVIg; apparent seroconversion; intravenous immunoglobulins; myositis.

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Conflict of interest statement

I. M. Lucke has nothing to disclose. A. Vrijlandt has nothing to disclose. J. Lim reports financial support from Sanquin for attending a conference, not related to the submitted work. A. J. van der Kooi reports grants from CSL Behring, outside the submitted work. I. N. van Schaik reports grants from Prinses Beatrix Spierfonds, grants from the Netherlands Organization for Scientific Research, and another from CSL Behring, all outside the submitted work. H. Zaaijer has nothing to disclose. J. W. Hovius reports grants from Bio‐Rad Laboratories, grants from the Netherlands Organization for Health Research and Development, and grants from the European Regional Development Fund (INTERREG), outside the submitted work. F. Eftimov reports grants from Prinses Beatrix Spierfonds, the Netherlands Organization for Health Research and Development, a consulting fee from CSL Behring and UCB Pharma that was paid to the author’s institution outside the submitted work, grants from CSL Behring, Kedrion, Terumo BCT, Grifols and Takeda Pharmaceutical Company, outside the submitted work. Grants were paid to the institution and are used for investigator‐initiated studies within INCbase, an international CIDP registry.

Figures

FIGURE 1
FIGURE 1
Quantitative C6 Lyme index in patients treated with intravenous immunoglobulin (IVIg) or dexamethasone. (a) Patients treated with Nanogam®. (b) Patients treated with Privigen®. (c) Patients treated with dexamethasone. Cutoff values recommended by the manufacturer are depicted by the dotted lines; C6 Lyme index ≤0.90 is considered a negative result, 0.90–1.09 an equivocal result and ≥1.10 a positive result [Colour figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

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