The Immunomodulatory Role of Therapeutic Plasma Exchange in Peripheral Nervous System and Neuromuscular Diseases

European Neurological Review, 2017;12(Suppl. 1):2–7

Abstract:

This article reports the proceedings of a satellite symposium held on 7 July 2016 at the 14th International Congress on Neuromuscular Diseases (ICNMD) symposium, Toronto, Canada. Therapeutic plasma exchange (TPE) removes pathogenic antibodies and immune complexes from the plasma. However, TPE may also impact a number of other immune-modulatory pathways that mediate cellular immunity. Data from clinical trials support the effectiveness of TPE in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, to date, the use of TPE for the treatment of chronic myasthenia gravis (MG) is not supported by large clinical studies and there are discrepancies between guidelines and clinical practice. More clinical trials are needed to understand the role of TPE in MG, GBS, and CIDP, as well as other neuromuscular diseases in which it is used, or which may represent potential targets for TPE.
Keywords: Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, myasthenia gravis, plasma exchange
Disclosure: Luis Querol received a scientific award from Grifols. Mazen M Dimachkie is on the speaker’s bureau or is a consultant for Alnylam, Baxalta, Catalyst, CSL-Behring, Mallinckrodt, Novartis NuFactor and Terumo BCT. He has also received grants from Alexion, Biomarin, Catalyst, CSL-Behring, FDA/OPD, GSK, Grifols, MDA, NIH, Novartis & TMA. Jean-Marc Leger acted as a consultant or received departmental research grants from Baxalta, CSL-Behring, LFB, Novartis, Terumo BCT and UCB. This article reports the proceedings of a sponsored satellite symposium held at the 14th International Congress on Neuromuscular Diseases symposium, Toronto, Canada, 7 July 2016 and, as such, has not been subject to this journal’s usual peer-review process. A member of the editorial board reviewed the report before publication.
Acknowledgments: Writing assistance was provided by Katrina Mountfort, Touch Medical Media, funded by Terumo BCT.
Received: December 15, 2016 Published Online: February 01, 2017
Correspondence: Mazen M Dimachkie, The University of Kansas Medical Center, Kansas City, Kansas, US. E: mdimachkie@kumc.edu
Support: The publication of this article was funded by Terumo BCT.
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.
Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.

Therapeutic plasma exchange (TPE) is a valuable technique in peripheral nervous system and neuromuscular diseases: the removal of autoantibodies and immune complexes ensures a rapid onset of action, and the treatment is safe and effective for long-term use. However, the mechanism of action of TPE involves more than the removal of large molecules; studies have shown that TPE has numerous immunomodulatory effects. Despite the fact that TPE is widely used in the treatment of neurological diseases, its effectiveness has only been formally demonstrated in a limited number of conditions: myasthenia gravis (MG), Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). This article describes the proceedings of a symposium convened at the 14th International Congress on Neuromuscular Diseases (ICNMD) symposium, in Toronto, Canada on 7 July 2016. The symposium aimed to further explore the immunomodulatory role of TPE, and to discuss current clinical evidence and unmet needs.

Luis Querol began his presentation by defining several terms that are often used interchangeably in the literature. Apheresis is derived from the Greek term aphaeresis, meaning to take away by force. Plasmapheresis refers to the removal of small volumes of plasma, not more than 15% of total blood volume (TBV), without necessarily replacing the volume. Therapeutic plasma exchange (the abbreviation TPE will be used in this report though PLEX, PE and PEX are also used to mean TPE) is the removal of large volumes of plasma (1 to 1.5 of patients’ TBV) with appropriate volume replacement using either albumin or fresh frozen plasma (FFP).1

Separation of blood components by TPE may employ a centrifuge or membrane filtration. The major differences between the two techniques are the plasma volumes required: centrifuge techniques require lower volumes than membrane and allow a higher plasma extraction rate, which affects the procedural time and the effectiveness of the procedure. Centrifuge TPE usually employs citrate as anticoagulation factor while membrane TPE employs heparin. In addition, centrifuge-based TPE requires a lower blood flow than membrane-based TPE (<150 ml/min versus >150 ml/min). As a result, centrifuge-based TPE can be performed successfully using peripheral venous access.2

The World Apheresis Association (WAA) apheresis registry now comprises data from 50,846 procedures performed in 7,142 patients, of which 16,942 were TPE.3 Most adverse events (AEs) associated with the procedure were reversible and mild in 2.4% of procedures, and included: vascular access problems (54%), device issues (7%), hypotension (15%) and tingling (8%). Moderate AEs were reported in in 3% of procedures and included: tingling (58%), urticaria (15%), hypotension (10%) and nausea (3%). In this registry, severe AEs occurred in only 0.4% of procedures: syncope/hypotension (32%), urticaria (17%), chills/fever (8%), arrhythmia/ asystole (4.5%), nausea/vomiting (4%). Centrifuge-based techniques are much more commonly used than membrane filtration (16:1) and are associated with fewer AEs (6% versus 11%). Procedures performed with central venous access are associated with more severe AEs compared with peripheral access.3

Despite its use in a variety of diseases, and the fact that the use of TPE dates back to the 1950s, its mechanism of action has only been evaluated in a limited number of small studies. While the early use of TPE involved the bulk removal of pathological substances, this action does not explain all of its therapeutic effects, particularly in neuromuscular conditions.4 Plasma exchange has the ability to modulate several immune mechanisms on which other drugs act individually. These are complementary to each other and include the removal of autoantibodies, immune complexes, cytokines etc. that control homeostasis and help to restore the patient’s immune function to normal (see Figure 1).5 In addition to the removal of pathogenic antibodies and circulating immune complexes, TPE also involves modification of immune complex structure and processing by changing the antigen/antibody ratio; modulation of immune complex solubility via complement activation; and modification of cellular components such as lymphocyte subsets.6

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Keywords: Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, myasthenia gravis, plasma exchange