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Immunoparesis in IgM gammopathies as a useful biomarker to predict disease progression

  • Marcio Andrade-Campos , Ilda Murillo-Flórez , Ramón García-Sanz and Pilar Giraldo EMAIL logo
Published/Copyright: March 11, 2017
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 55 Issue 10

Abstract

Background:

The management of IgM monoclonal gammopathies undetermined significance (IgM-MGUS) and Waldenstrom’s macroglobulinemia (WM) may be challenging. Modern immunoassays that quantify specific monoclonal heavy and light chain immunoglobulins are promising for their use in these applications.

Methods:

Ninety consecutive patients (39 IgM-MGUS, 32 indolent WM [iWM], and 19 WM) seen between January 2007 and March 2014 were analyzed. Heavy/light chain (HLC) and serum free light chains assays (FLC) were determined at diagnosis to study their utility as biomarkers in IgM monoclonal gammopathies.

Results:

The HLC involved to uninvolved IgM ratios (iHLC/uHLC) showed a progressive increase when going from IgM-MGUS, to iWM and to WM (p=0.002). Furthermore, an iHLC/uHLC>62 identified a group of iWM patients with a shorter time-to-progression (TTP) (108 vs. 133 months, p=0.033). Separate analysis of the involved and uninvolved components showed that only the suppression of the uninvolvedimmunoglobulin was predictive of shorter TTP (HR=3.04, p=0.03) suggesting that it could be the majorcontributor to the prognostic value of the Hevylite assay. Additionally, a multivariate analysis showed that immunosuppression (either classical immunoparesis or Hevylite immunosuppression) was an independent prognostic factor (p=0.016) reinforcing its relevance in the disease mechanism. Finally, monoclonal sFLC levels were highest in WM patients, with 83% presenting values>60 mg/L.

Conclusions:

The results suggest that the levels of immunosuppression and/or the iHLC/uHLC ratio of IgM immunoglobulins measured by Hevylite are associated with greater disease activity which significantly impacts in the outcome of WM patients and may also help in the differentiation of IgMMGUS from iWM.

Keywords: free light chain; IgM heavy/light chain; IgM monoclonal gammopathy
Corresponding author: Pilar Giraldo, Traslational Research Unit, Instituto de Investigación Sanitaria Aragón (ISS-A), P° Isabel La Católica 1-3, 50009 Zaragoza, Spain, Phone: +34670285339
aMarcio Andrade-Campos and Ilda Murillo-Flórez should be regarded as joint first authors.

Acknowledgments

We want to thank personnel from the Biobank of the Aragon Health System, Izaskun Arenaz and Laura Soler Duque (technical support). Thanks also to the Miguel Servet University Hospital Library for providing documentary support. This work has been partially supported by FEHHA.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2016-8-22
Accepted: 2017-1-25
Published Online: 2017-3-11
Published in Print: 2017-8-28

©2017 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2016-0748
Keywords for this article
free light chain; IgM heavy/light chain; IgM monoclonal gammopathy

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  1. Frontmatter
  2. Editorials
  3. Reporting LDL-cholesterol levels in the era of intensive lipid management: a clarion call
  4. The challenges of genetic risk scores for the prediction of coronary heart disease
  5. Reviews
  6. Advanced lipoprotein testing for cardiovascular diseases risk assessment: a review of the novel approaches in lipoprotein profiling
  7. A review of the challenge in measuring and standardizing BCR-ABL1
  8. Mini Review
  9. Challenges in the analysis of epigenetic biomarkers in clinical samples
  10. Opinion Paper
  11. Defining a roadmap for harmonizing quality indicators in Laboratory Medicine: a consensus statement on behalf of the IFCC Working Group “Laboratory Error and Patient Safety” and EFLM Task and Finish Group “Performance specifications for the extra-analytical phases”
  12. Genetics and Molecular Diagnostics
  13. Assessment of EGFR mutation status using cell-free DNA from bronchoalveolar lavage fluid
  14. General Clinical Chemistry and Laboratory Medicine
  15. A survey of patients’ views from eight European countries of interpretive support from Specialists in Laboratory Medicine
  16. Verification of examination procedures in clinical laboratory for imprecision, trueness and diagnostic accuracy according to ISO 15189:2012: a pragmatic approach
  17. Expressing analytical performance from multi-sample evaluation in laboratory EQA
  18. A candidate reference method for serum potassium measurement by inductively coupled plasma mass spectrometry
  19. Practical motives are prominent in test-ordering in the Emergency Department
  20. Technical and clinical validation of the Greiner FC-Mix glycaemia tube
  21. Comparison of pneumatic tube system with manual transport for routine chemistry, hematology, coagulation and blood gas tests
  22. Accuracy of cerebrospinal fluid Aβ1-42 measurements: evaluation of pre-analytical factors using a novel Elecsys immunosassay
  23. Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry
  24. Analytical performance and diagnostic accuracy of six different faecal calprotectin assays in inflammatory bowel disease
  25. Novel immunoassays for detection of CUZD1 autoantibodies in serum of patients with inflammatory bowel diseases
  26. Hematology and Coagulation
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  28. Reference Values and Biological Variations
  29. Reference ranges of thromboelastometry in healthy full-term and pre-term neonates
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