The heavy chain/light chain assay (HLC) is a useful biomarker to diagnose and manage patients with cold agglutinin disease (CAD), according to the results of a new study published in the British Journal of Haematology

HLC is an alternative assay to detect, identify and quantify monoclonal immunoglobulins (Igs) that are both involved and uninvolved. The usefulness of the assay has been demonstrated in IgA myeloma but is not well characterized in CAD.

Here, a team of researchers from Saint-Louis Hospital in Paris, France led by Bertrand Arnulf, MD, PhD, compared the efficacy of HLC with that of serum protein electrophoresis (SPE) and immunofixation (IFX) in detecting and monitoring IgM monoclonal component in patients with CAD, a disease characterized by the production of a monoclonal cold agglutinin IgM.

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To this aim, the researchers retrospectively analyzed all patients who were diagnosed with CAD in their hospital between 1993 and 2018. A total of 48 patients were diagnosed with CAD during this time and were included in the analysis. SPE, IFX, and HLC assays were done in all patients.

Read more about the diagnosis of CAD

The results showed that SPE yielded positive results in 18 patients corresponding to a little more than a third (37.5%) of all patients. IFX detected monoclonal IgM in more than half (52.1%) of patients (a total of 25) and the HLC ratio was found to be abnormal in 32 patients. IFX and SPE detected monoclonal components in 15 patients corresponding to 62.5% of all patients.

“In 8 patients, IgM was missed by IFX while detected by HLC,” the researchers reported. Similarly, IgM was missed in 17 patients by SPE but detected by HLC.

Based on these findings, the researchers concluded that the detection of IgM-monoclonal components is significantly higher using the HLC ratio than using SPE or IFX.


Ursule-Dufait C, Bengoufa D, Theodorou I, Villesuzanne C, Arnulf B. Heavy chain/light chain assay is a useful biomarker for diagnosis and management of patients with cold agglutinin disease. Br J Haematol. Published online June 22, 2022. doi:10.1111/bjh.18317