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Effects of IVIg treatment on autoantibody testing in neurological patients: marked reduction in sensitivity but reliable specificity

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Abstract

Background

Therapy of autoimmune diseases of the central and peripheral nervous system with intravenous IgG immunoglobulin (IVIg) is well established. Since IVIg is produced from pooled human plasma, autoantibodies can be found in IVIg products and, accordingly, in patient sera after transfusion. The de novo evidence or disappearance of anti-neural autoantibodies after IVIg treatment has so far not been systematically examined.

Methods

We screened 50 neurological patients before and after IVIg treatment for classical onconeural and the most common neurological surface autoantibodies as well as for ganglioside autoantibodies and 23 different antinuclear autoantibodies using immunoblot or cell-based indirect immunofluorescence assays. Furthermore, we screened 31 neurological patients with previously known seropositivity for disappearance of the corresponding antibody after treatment.

Results

After IVIg treatment, 90% of all sera were de novo positive for antinuclear antibodies, especially for Ro-52. In contrast, 94% of all sera did not show any de novo-positive anti-neural antibodies. In the remaining three cases, titers were very low. Importantly, 12.9% of all tested sera of patients with known antibody positivity turned false negative after IVIg treatment and titers were falsely low in 37% of the remaining sera.

Conclusions

Here, we present for the first time results of a broad screening for clinically relevant autoantibodies before and after IVIg treatment in neurological patients. We identified a high specificity but reduced sensitivity for anti-neural antibody testing after IVIg transfusion. In contrast, antinuclear antibody testing is not reliable after IVIg treatment. These results are of high practical importance for diagnostic of neuroimmunological diseases.

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Funding

The study was not funded externally.

Author information

Author notes

  1. Lars Komorowski and Ilya Ayzenberg contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany

    Thomas Grüter, Markus Kinner, Jeremias Motte, Kalliopi Pitarokoili, Ralf Gold & Ilya Ayzenberg

  2. Institute for Experimental Immunology, Lübeck, Germany

    Anthonina Ott, Wolfgang Meyer & Lars Komorowski

  3. Molecular Neuroimmunology Group, Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany

    Sven Jarius

  4. Department of Neurology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia

    Ilya Ayzenberg

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  1. Thomas Grüter
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Contributions

TG participated in serum collection, acquisition of data, analysis and interpretation of data, study design and draft and revision of the manuscript for content. AO and WM performed antibody testing and participated in the revision of the manuscript for content. SJ drafted and revised the manuscript for content. MK participated in serum collection, acquisition of data, analysis and interpretation of data, study design and draft and revision of the manuscript for content. JM participated in serum collection, draft and revision of the manuscript for content. KP and RG drafted and revised the manuscript for content. LK participated in antibody testing, study design and draft and revision of the manuscript for content. IA conceived the idea, designed and directed the project, and participated in serum collection, acquisition of data, analysis and interpretation of data, draft and revision of the manuscript for content.

Corresponding author

Correspondence to Ilya Ayzenberg.

Ethics declarations

Conflicts of interest

TG received travel reimbursement from Sanofi Genzyme and Biogen Idec, none related to this manuscript. AO is employee of EUROIMMUN AG, a company that develops, manufactures and markets serological assays for the determination of autoantibodies. WM is employee of EUROIMMUN AG, a company that develops, manufactures and markets serological assays for the determination of autoantibodies. SJ reports no conflicts of interest. MK received a travel grant from Biogen idec, not related to this study. JM received travel grants from Biogen Idec, Novartis AG, Teva and Eisai GmbH, his research is funded by Klaus Tschira Foundation and Ruhr-University, Bochum (FORUM-program); none related to this work. KP received travel funding and speaker honoraria from Biogen Idec, Novartis and Bayer Schering Pharma and funding from the Ruhr-University, Bochum (FORUM-Program), none related to this manuscript. RG serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis, none related to this manuscript. LK is employee of EUROIMMUN AG, a company that develops, manufactures and markets serological assays for the determination of autoantibodies. IA received travel grants from Biogen Idec and Guthy-Jackson Charitable Foundation, served on scientific advisory boards for Roche and Alexion and received research support from Chugai Pharma, none related to this manuscript.

Ethical standards

The study has been approved by the local ethics committee (Ethik-Kommission Ruhr-Universität Bochum) and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.

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Grüter, T., Ott, A., Meyer, W. et al. Effects of IVIg treatment on autoantibody testing in neurological patients: marked reduction in sensitivity but reliable specificity. J Neurol 267, 715–720 (2020). https://doi.org/10.1007/s00415-019-09614-4

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  • DOI: https://doi.org/10.1007/s00415-019-09614-4

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