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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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1437-4331
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Volume 54, Issue 6

Issues

Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation

Maria Alice V. Willrich
  • Corresponding author
  • Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Paula M. Ladwig
  • Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Bruna D. Andreguetto / David R. Barnidge
  • Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ David L. Murray
  • Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jerry A. Katzmann
  • Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Melissa R. Snyder
  • Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-01-21 | DOI: https://doi.org/10.1515/cclm-2015-1023

Abstract

Background: The use of therapeutic recombinant monoclonal antibodies (mAbs) has triggered concerns of mis-diagnosis of a plasma cell dyscrasia in treated patients. The purpose of this study is to determine if infliximab (INF), adalimumab (ADA), eculizumab (ECU), vedolizumab (VEDO), and rituximab (RITU) are detected as monoclonal proteins by serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE).

Methods: Pooled normal sera were spiked with various concentrations (ranging from trough to peak) of INF, ADA, ECU, VEDO and RITU. The peak concentration for VEDO and RITU was also added to samples with known monoclonal gammopathies. All samples were analyzed by SPEP (Helena Laboratories) and IFE (Sebia); sera containing peak concentrations of mAbs were reflexed to electrospray-time-of-flight mass spectrometry (AbSciex Triple TOF 5600) for the intact light chain monoclonal immunoglobulin rapid accurate mass measurement (miRAMM).

Results: For all mAbs tested, no quantifiable M-spikes were observed by SPEP at any concentration analyzed. Small γ fraction abnormalities were noted on SPEP for VEDO at 300 μg/mL and RITU at 400 μg/mL, with identification of small IgG κ proteins on IFE. Using miRAMM for peak samples, therapeutic mAbs light chain accurate masses were identified above the polyclonal background and were distinct from endogenous monoclonal gammopathies.

Conclusions: MAbs should not be easily confounded with plasma cell dyscrasias in patients undergoing therapy except when a SPEP and IFE are performed within a couple of days from infusion (peak). In ambiguous cases the use of the miRAMM technology could precisely identify the therapeutic mAb distinct from any endogenous monoclonal protein.

Keywords: immunofixation; monoclonal antibody therapies; monoclonal immunoglobulin Rapid Accurate Mass Measurement (miRAMM); protein electrophoresis

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About the article

Corresponding author: Maria Alice V. Willrich, PhD, Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA, Phone: +507-266-4909, Fax: +507-266-4088


Received: 2015-10-19

Accepted: 2015-12-13

Published Online: 2016-01-21

Published in Print: 2016-06-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 54, Issue 6, Pages 1085–1093, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2015-1023.

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