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Molecular typing of cryoglobulins by mass spectrometry
  1. Adrian YS Lee1,2,
  2. Tim Chataway3,
  3. Thomas P Gordon1,2,
  4. Jing Jing Wang1,2
  1. 1 Department of Immunology, SA Pathology (Flinders Medical Centre), Bedford Park, SA, Australia
  2. 2 Department of Immunology, Flinders University, Bedford Park, SA, Australia
  3. 3 Flinders Proteomics Facility, Flinders University, Bedford Park, SA, Australia
  1. Correspondence to Dr Jing Jing Wang, Department of Immunology, SA Pathology and Flinders University, Adelaide, SA 5042, Australia; wang0524{at}

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A cause of potentially devastating pathologies, cryoglobulins are immunoglobulin complexes that precipitate out of serum at temperatures lower than 37°C. They often arise secondary to underlying conditions, such as hepatitis infections, although may be idiopathic. Brouet et al 1 classified cryoglobulins according to their immunoglobulin composition: type I (monoclonal), type II (mixed with monoclonal rheumatoid factor (RF)) and type III (mixed with polyclonal RF).

Detection of cryoglobulins has not changed in decades and as a multistep process, is fraught with problems and a lack of universal standardisation to preanalytic handling. Currently, electrophoresis and immunofixation methods are used to characterise cryoglobulins. These techniques are unable to resolve and track specific clonotypes which can mutate and change pathogenicity over time.

Mass spectrometry (MS) may be used to molecularly type IgM RFs in cryoglobulins.2 Using an MS-based proteomic approach, we recently identified the immunoglobulin heavy chain variable region (IGHV) subfamilies and mutational …

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  • Handling editor Josef S Smolen

  • Contributors All the authors contributed substantially to the manuscript and were involved in concept development, data collection and analyses, and manuscript drafting. All the authors have approved the final version of the manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding This work was supported by an Australian National Health and Medical Research Council (NHMRC) project grant (1041900) and an NHMRC Early Career Fellowship grant (1090759).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Clinical Ethics Committee of the Flinders Medical Centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.