Heat-resistant cryoglobulin investigated through dynamic cryoaggregation assay and mass spectrometry

Cryoglobulins are immune complexes of antibodies that precipitate from serum at temperatures less than 37 °C. In the diagnostic laboratories, the usual method for the detection of cryoglobulins is the observation of a serum precipitate when left for several days at 4 °C. Dissolution of the precipitate when warmed at 37 °C is confirmation that the precipitate is cryoglobulin immune complexes. We report a rare case of heat-resistant type II cryoglobulin in an asymptomatic patient with chronic hepatitis C, that effectively solubilised at 42 °C. Mass spectrometric typing revealed this to be a minimally mutated cryoglobulin of the Wa-idiotype. This case emphasises the importance of laboratorians to be aware of rare cases of heat-resistant cryoglobulins to avoid false negative results.