Protein Diagnostics

  • Chapter
  • First Online:
Clinical and Laboratory Medicine Textbook

Abstract

Protein diagnostics mainly deals with monoclonal gammopathies, conditions characterized by the presence of a monoclonal immunoglobulin (or part of it) in the blood or in the urine. This chapter first examines the clinical relevance of the condition, which ranges from clinically occult forms, represented by monoclonal gammopathy of undetermined significance, to forms in which the clinical condition is determined by effects due to the peculiar characteristics of monoclonal immunoglobulin, to true neoplasms, such as multiple myeloma. Then the laboratory techniques that allow the management of patients with monoclonal gammopathy are described: protein electrophoresis (serum and urine), for the detection and quantification of the monoclonal component; immunological ty**, for the definition of the class and type of immunoglobulin involved; measurement of serum-free light chains and of the immunoglobulins not involved in monoclonality. In the second part, the other field of protein diagnostics is introduced, i.e., the measurement of some clinically relevant serum proteins. Those taken into consideration are albumin, α1-antitrypsin, haptoglobin, β2-microglobulin, ceruloplasmin, complement, immunoglobulins, C-reactive protein, transthyretin. For each of these, a summary of the physicochemical characteristics and biological function is presented as well as indications for their appropriate clinical use.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Recommended Readings

  • Aguzzi F, Poggi N (1977) Immunosubtraction electrophoresis: a simple method for identifying specific proteins producing the cellulose acetate electrophoretograms. Boll Ist Sieroter Milan 56:212–216

    CAS  PubMed  Google Scholar 

  • AIRTUM Working Group (2016) Rapporto AIRTUM 2015. The burden of rare cancers in Italy. Epidemiol Prev 40(Suppl 2):1–120

    Google Scholar 

  • Aletaha D, Smolen JS (2018) Diagnosis and management of rheumatoid arthritis: a review. JAMA 320:1360–1372

    Article  PubMed  Google Scholar 

  • Aringer M, Costenbader K, Daikh D et al (2019) 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 78:1151–1159

    Article  PubMed  Google Scholar 

  • Berggård B, Björck L, Cigén R (1980) Beta-2 microglobulin. Scand J Clin Lab Invest Suppl 154:13–25

    PubMed  Google Scholar 

  • Bradwell AR, Carr-Smith HD, Mead GP et al (2001) Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 47:673–680

    Article  CAS  PubMed  Google Scholar 

  • Caraceni P, Angeli P, Prati D et al (2016) AISF-SIMTI position paper: the appropriate use of albumin in patients with liver cirrhosis. Blood Transfus 14:8–22

    PubMed  PubMed Central  Google Scholar 

  • Dati F, Schuman G, Thomas L et al (1996) Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardisation against IFCC/BCR/CAP reference material (CRM 470). Eur J Clin Chem Clin Biochem 34:517–520

    CAS  PubMed  Google Scholar 

  • European Association for the Study of the Liver (2009) EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 51:237–267

    Article  Google Scholar 

  • European Association for the Study of the Liver (2012) EASL Clinical Practice Guidelines: Wilson’s disease. J Hepatol 56:671–685

    Article  Google Scholar 

  • Fermand JP, Bridoux F, Dispenzieri A et al (2018) Monoclonal gammopathies of clinical significance: a novel concept with therapeutic implications. Blood 132:1478–1485

    Article  CAS  PubMed  Google Scholar 

  • Gomollón F, Dignass A, Annese V et al (2017) 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: part 1: diagnosis and medical management. J Crohns Colitis 11:3–25

    Article  PubMed  Google Scholar 

  • Graziani MS (2016) Measurement of free light chains: pros and cons of current methods. Clin Chem Lab Med 54:1015–1020

    Article  CAS  PubMed  Google Scholar 

  • Graziani MS, Merlini GP (2013) Recommendations for appropriate serum electrophoresis requests: the Italian approach. Clin Chem Lab Med 51:e117–e118

    Article  CAS  PubMed  Google Scholar 

  • Graziani MS, Merlini G, Petrini C, for the IFCC Committee on Plasma Proteins and the SIBioC Study Group on Proteins (2003) Guidelines for the analysis of Bence Jones protein. Clin Chem Lab Med 41:38–46

    Article  Google Scholar 

  • Hellman N, Gitlinn J (2002) Ceruloplasmin metabolism and function. Annu Rev Nutr 22:439–458

    Article  CAS  PubMed  Google Scholar 

  • Jacobs JFM, Turner KA, Graziani MS et al (2020) An international multi-center serum protein electrophoresis accuracy and M-protein isoty** study. Part II: limit of detection and follow-up of patients with small M-proteins. Clin Chem Lab Med 58:547–593

    Article  CAS  PubMed  Google Scholar 

  • Johansson BG (1972) Agarose gel electrophoresis. Scand J Clin Lab Invest 29:7–21

    Article  CAS  Google Scholar 

  • Katzmann JA (2009) Screening panels for monoclonal gammopathies: time to change. Clin Biochem Rev 30:105–111

    PubMed  PubMed Central  Google Scholar 

  • Katzmann JA, Kyle RA, Benson J et al (2009) Screening panels for detection of monoclonal gammopathies. Clin Chem 55:1517–1522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kyle RA (1978) Monoclonal gammopathy of undetermined significance. Natural history in 241 cases. Am J Med 64:814–826

    Article  CAS  PubMed  Google Scholar 

  • Landers JP (1995) Clinical capillary electrophoresis. Clin Chem 41:495–509

    Article  CAS  PubMed  Google Scholar 

  • Lanzillotta M, Mancuso G, Della-Torre E (2020) Advances in the diagnosis and management of IgG4 related disease. BMJ 369:m1067

    Article  PubMed  Google Scholar 

  • Merlini G, Stone MJ (2006) Dangerous small B-cell clones. Blood 108:2520–2530

    Article  CAS  PubMed  Google Scholar 

  • Miravitlles M, Asger Dirksen A, Ferrarotti I et al (2017) European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1-antitrypsin deficiency. Eur Respir J 50:1700610

    Article  PubMed  Google Scholar 

  • Murray DL, Puig N, Kristinsson S et al (2021) Mass spectrometry for the evaluation of monoclonal proteins in multiple myeloma and related disorders: an International Myeloma Working Group Mass Spectrometry Committee Report. Blood Cancer J 11:24. https://doi.org/10.1038/s41408-021-00408-4

    Article  PubMed  PubMed Central  Google Scholar 

  • Napodano C, Gulli F, Ludovico G et al (2021) Cryoglobulins: identification, classification, and novel biomarkers of mysterious proteins. Adv Clin Chem 104:299–340

    Article  CAS  PubMed  Google Scholar 

  • National Kidney Foundation. KDOQI clinical practice guideline for hemodialysis: 2015 update. https://www.kidney.org/professionals/guidelines/hemodialysis2015. Last accessed: March 2020

  • Palumbo A, Avet-Loiseau H, Oliva S et al (2015) Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol 33:2863–2869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest 111:1805–1812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Picard C, Al-Herz W, Bousfiha A et al (2015) Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin Immunol 35:696–726

    CAS  Google Scholar 

  • Rajkumar SV, Dimopoulos MA, Palumbo A et al (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15:e538–e548

    Article  PubMed  Google Scholar 

  • Ranasinghe RN, Biswas M, Vincent RP (2022) Prealbumin: the clinical utility and analytical methodologies. Ann Clin Biochem 59:7–14

    Article  CAS  PubMed  Google Scholar 

  • Rapporto AIOM-AIRTOM (2021) I numeri del cancro in Italia 2020. https://www.aiom.it/wp-content/uploads/2020/10/2020_Numeri_Cancro-operatori_web.pdf. Last accessed: March 2022

  • Rishi K, Wadhera RK, Phil M et al (2010) Prevalence of monoclonal gammopathy of undetermined significance: a systematic review. Mayo Clin Proc 85:933–942

    Article  Google Scholar 

  • Ritchie RF, Smith R (1976) Immunofixation. I. General principles and application to agarose gel electrophoresis. Clin Chem 22:497–499

    Article  CAS  PubMed  Google Scholar 

  • Rothschild MA, Oratz M, Schreiber SS (1972) Albumin synthesis. N Eng J Med 286:816–821

    Article  CAS  Google Scholar 

  • Shih AWY, McFarlane A, Verhovsek M (2014) Haptoglobin testing in hemolysis: measurement and interpretation. Am J Hematol 89:443–447

    Article  CAS  PubMed  Google Scholar 

  • Silverman EK, Sandhaus RA (2009) α1-antitrypsin deficiency. N Engl J Med 360:2749–2757

    Article  CAS  PubMed  Google Scholar 

  • Sun L, Pennells L, Kaptoge S et al (2021) Polygenic risk scores in cardiovascular risk prediction: a cohort study and modelling analyses. PLoS Med 18:e1003498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swain S, Selmi C, Gershwin ME et al (2019) The clinical implications of selective IgA deficiency. J Transl Autoimmun 2:100025

    Article  PubMed  PubMed Central  Google Scholar 

  • Tate J, Caldwell G, Daly J et al (2012) Recommendations for standardized reporting of protein electrophoresis in Australia and New Zealand. Ann Clin Biochem 49:242–256

    Article  CAS  PubMed  Google Scholar 

  • Touzeau C, Moreau P, Dumontet C (2017) Monoclonal antibody therapy in multiple myeloma. Leukemia 31:1039–1047

    Article  CAS  PubMed  Google Scholar 

  • Turner KA, Frinack JL, Ettore MW et al (2020) An international multi-center serum protein electrophoresis accuracy and M-protein isoty** study. Part I: factors impacting limit of quantitation of serum protein electrophoresis. Clin Chem Lab Med 58:533–546

    Article  CAS  PubMed  Google Scholar 

  • Vidya Sarma J, Peter A, Ward PA (2011) The complement system. Cell Tissue Res 343:227–235

    Article  PubMed  Google Scholar 

  • Watson J, Round A, Hamilton W (2012) Raised inflammatory markers. BMJ 344:e454

    Article  PubMed  Google Scholar 

  • Weiss BM, Abadie J, Verma P et al (2009) A monoclonal gammopathy precedes multiple myeloma in most patients. Blood 113:5418–5422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiedermann CJ, Wiedermann W, Michael Joannidis M (2017) Causal relationship between hypoalbuminemia and acute kidney injury. World J Nephrol 6:176–187

    Article  PubMed  PubMed Central  Google Scholar 

  • Willerson JT, Ridker PM (2004) Inflammation as a cardiovascular risk factor. Circulation 109(21 Suppl 1):II2–I10

    PubMed  Google Scholar 

  • Willrich MAV, Katzmann JA (2016) Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias. Clin Chem Lab Med 54:907–919

    Article  CAS  PubMed  Google Scholar 

  • Zajec M, Langerhorst P, VanDuijn MM et al (2020) Mass spectrometry for identification, monitoring, and minimal residual disease detection of M-proteins. Clin Chem 66:421–433

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria Stella Graziani .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Graziani, M.S., Caldini, A. (2023). Protein Diagnostics. In: Ciaccio, M. (eds) Clinical and Laboratory Medicine Textbook. Springer, Cham. https://doi.org/10.1007/978-3-031-24958-7_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-24958-7_12

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-24957-0

  • Online ISBN: 978-3-031-24958-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Navigation