Hevylite Blood Test May Help in CAD Diagnosis

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Illustration of blood in a pipette and test tubes.

A test called Hevylite was superior to standard methods at detecting immunoglobulin M (IgM) — a type of antibody associated with cold agglutinin disease (CAD) — in the blood of people with the disease, a small study has shown.

This suggests that Hevylite, sold by Binding Site, may help in the diagnosis and management of CAD patients, the researchers noted.

The study, “Heavy chain/light chain assay is a useful biomarker for diagnosis and management of patients with cold agglutinin disease,” was published as a letter in the British Journal of Haematology by a team of researchers in France.

In people with CAD, the immune system abnormally produces self-reactive antibodies, called cold agglutinins, that bind to red blood cells when exposed to cold temperatures. This promotes the formation of red blood cell clumps that trigger immune reactions against them, leading to their destruction.

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Antibodies, or immunoglobulins (Igs), are produced by an immune cell called a B-cell to help the body fight infection or foreign invaders. In autoimmune disease such as CAD, some of these antibodies mistakenly target a person’s own molecules or tissues.

Each antibody is made up of two copies of a light chain, that can be classified as kappa or lambda, and two copies of a heavy chain, which defines its type (IgA, IgD, IgE, IgG, or IgM).

Autoantibodies in CAD usually are monoclonal IgM. They are called monoclonal because they derive from a single B-cell.

Currently used methods to measure the levels of monoclonal IgM in the blood have low sensitivity, meaning they do not always do a good job of detecting the autoantibodies. This is especially true in people with CAD, “since IgM is often low and difficult to detect,” the researchers wrote.

Hevylite is a “quick, simple and highly sensitive laboratory [blood] test for measuring intact immunoglobulin monoclonal proteins,” Binding Site states in the test’s lab info page. This means it may be able to detect antibodies even if they are at very low levels in the blood.

The test measures specific combinations of heavy and light chain and calculates a ratio of kappa to lambda light chains. If the ratio differs from the normal range, it is said to be abnormal and indicates the presence of a monoclonal antibody.

Hevylite is approved by the U.S. Food and Drug Administration for monitoring people with myeloma, a cancer that arises from antibody-producing B-cells.

Comparing assays SPE and IFX

To find out how well Hevylite may measure monoclonal IgM in the blood of CAD patients, the researchers compared its results with those of two gold-standard assays: serum protein electrophoresis (SPE) and immunofixation (IFX).

Similar to Hevylite, SPE not only can detect, but also measure, the levels of monoclonal antibodies, while IFX can only detect.

The study included 48 patients (31 women and 17 men) diagnosed with CAD at a mean age of 62.3 years at Saint-Louis Hospital in Paris from 1993 to 2018.

Monoclonal gammopathy of undetermined significance, a condition defined by abnormally high levels of a monoclonal Ig, was the most common underlying disease, affecting 21 of the patients.

A total of 24 patients (50%) were receiving treatment for CAD. Half of them were given rituximab in combination with other mediations, eight received rituximab alone, and the remaining four were on other therapies. Rituximab, sold as Rituxin in the U.S., and MabThera in Europe, is a B-cell depleting therapy commonly used off-label for CAD.

Results showed that SPE detected monoclonal IgM in 15 (31.3%) patients and IFX in 25 (52.1%) patients.

Based on IFX, 23 patients had kappa light chain IgMs (IgM-kappa) and two had lambda light chain IgMs (IgM-lambda).

The Hevylite test came back positive for 32 (66.7%) patients: 25 with IgM-kappa and seven with IgM-lambda.

In 17 (35.4%) patients, monoclonal IgM was missed by SPE, but detected by Hevylite, and in eight (16.7%), it was missed by IFX but detected by Hevylite.

Overall, Hevylite was better for the detection of monoclonal IgM than SPE or IFX. Moreover, it identified a greater number of patients with IgM-lambda. “This is probably due to a better sensitivity of our assay,” the researchers wrote.

Five patients (one with IgM-lambda and four with IgM-kappa) were monitored with Hevylite over the course of their rituximab-based treatment. For all of them, test results were abnormal prior to treatment start, but returned to the normal range after treatment.

Hevylite “was useful to track the monoclonal component after treatment and was consistent with clinical improvement,” the researchers wrote.

For doctors, this could mean having a test that would allow them to foretell a potential relapse, or the return of symptoms after a period of improvement.

While the number of included patients was relatively small, these findings suggest that measurement of heavy and light chains “is a useful biomarker to detect and to follow the monoclonal component in either primary or secondary cold agglutinin disease,” the researchers concluded.