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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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