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Licensed Unlicensed Requires Authentication Published by De Gruyter July 24, 2023

Recommendations for the study of monoclonal gammopathies in the clinical laboratory. A consensus of the Spanish Society of Laboratory Medicine and the Spanish Society of Hematology and Hemotherapy. Part I: Update on laboratory tests for the study of monoclonal gammopathies

  • María C. Cárdenas ORCID logo EMAIL logo , Ramón García-Sanz , Noemí Puig , David Pérez-Surribas , Juan Flores-Montero , María Ortiz-Espejo , Javier de la Rubia and Elena Cruz-Iglesias


Monoclonal gammopathies (MG) are characterized by the proliferation of plasma cells that produce identical abnormal immunoglobulins (intact or some of their subunits). This abnormal immunoglobulin component is called monoclonal protein (M-protein), and is considered a biomarker of proliferative activity. The identification, characterization and measurement of M-protein is essential for the management of MG. We conducted a systematic review of the different tests and measurement methods used in the clinical laboratory for the study of M-protein in serum and urine, the biochemistry and hematology tests necessary for clinical evaluation, and studies in bone marrow, peripheral blood and other tissues. This review included literature published between 2009 and 2022. The paper discusses the main methodological characteristics and limitations, as well as the purpose and clinical value of the different tests used in the diagnosis, prognosis, monitoring and assessment of treatment response in MG. Included are methods for the study of M-protein, namely electrophoresis, measurement of immunoglobulin levels, serum free light chains, immunoglobulin heavy chain/light chain pairs, and mass spectrometry, and for the bone marrow examination, morphological analysis, cytogenetics, molecular techniques, and multiparameter flow cytometry.

Corresponding author: María C. Cárdenas, PhD, Department of Clinical Analysis, Institute of Laboratory Medicine, IdSSC, Hospital Clinico San Carlos, Madrid, Spain; and Protein Commission, Spanish Society of Laboratory Medicine (SEQCML), Barcelona, Spain, E-mail:

  1. Research funding: None declared.

  2. Author contribution: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: María C Cárdenas, Noemí Puig, David Pérez-Surribas, Juan Flores-Montero, María Ortiz-Espejo and Elena Cruz-Iglesias state no conflict of interest. Ramón García-Sanz states: Honoraria: Amgen, Millennium/Takeda, Janssen, Incyte, Astellas, BeiGene, AstraZeneca, Pfizer. Research funding: Novartis, Gilead, Astellas, Janssen. Advisory boards: Amgen, Pharmacyclics, Millennium/Takeda. Research support / PI: Spanish National Health System, Regional Health System (Castilla y León), Spanish Association Against Cancer. Ex-president: Spanish Society of Hematology and Hemotherapy. Employee: Spanish National Health System. Javier De la Rubia states: Honoraria: Takeda, Janssen, BMS, Pfizer, GSK, Oncopeptide, Sanofi. Research funding: Takeda. Advisory boards: Amgen, Janssen, Sanofi, GSK. Employee: Spanish National Health System.

  4. Informed consent: Not applicable.

  5. Research ethics: Not applicable.


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Supplementary Material

This article contains supplementary material (

Received: 2023-03-30
Accepted: 2023-05-29
Published Online: 2023-07-24
Published in Print: 2023-11-27

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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