Examining dendritic cells to uncover immunity defects

Eye on Innovation

Eye on Innovation features exciting advances taking place at Mayo Clinic Laboratories. This monthly series shines a spotlight on recently developed tests and highlights how Mayo Clinic translates ideas and discoveries into testing resources that improve diagnosis and care for patients across the globe.

Dendritic cells play a crucial role in the body's immune response. Research has shown that too few of these cells in the blood may signal a defect in innate immunity. Up to this point, however, no clinical test has been available to count dendritic cells.

Now Mayo Clinic Laboratories is offering clinicians a way to assess the number of both myeloid dendritic cells, or mDCs, and plasmacytoid dendritic cells, or pDCs, as well as monocytes, with its new Dendritic Cell and Monocyte Enumeration test — the only clinical test available in the United States for counting dendritic cells.

This first-of-its-kind test was developed in Mayo Clinic's Cellular and Molecular Immunology Laboratory. The lab's section director, Amir Sadighi Akha, M.D., D.Phil., notes that the test will be a valuable tool for uncovering rare immune disorders.

Amir Sadighi Akha,
M.D., D.Phil.

"The main intention for creating this test was to use it in the context of primary immune deficiencies," Dr. Sadighi Akha says. "Those are diseases where you have a defect in the development of the immune system, where one or both of the dendritic cell subsets are not produced. Monocytes are included in the test because there are a number of diseases where monocytes go up or down in tandem with differences in the dendritic cells."

The test can be used as part of an assessment for conditions such as GATA2 deficiency, IKZF1 deficiency, IRF8 deficiency, STAT3 gain-of-function disease, and HYOU1 deficiency, among others.

Dendritic cell enumeration is a noteworthy advance in the process of diagnosing these uncommon disorders. "Because it's a clinical test, it has gone through the rigorous set of necessary validations. We have a reference range for it with over 140 adults and over 60 children included," Dr. Sadighi Akha says. "It's a different case when you have a patient suspected of a disease, and you base your diagnosis on comparing that person, who you believe has a sickness, to somebody who presumably does not. This test is based on a broad number of reference subjects."

Beyond diagnosis of immune disorders, researchers at Mayo Clinic are studying the test for potential use in predicting the outcome of a COVID-19 infection. This work is one of a number of COVID-19 innovation projects supported by Mayo Clinic's Advanced Diagnostics Laboratory. Recently published studies have found that people with severe COVID-19 have fewer plasmacytoid dendritic cells and produce less interferon type 1 — an infection-fighting substance pDCs make. That may point to a connection between decreased pDC function and more severe infection.

"Our study in relation to the utility of this test in COVID-19 patients is ongoing," Dr. Sadighi Akha says. "If you base your conclusions on literature from others, it would make sense that the test could have some use for individuals with severe COVID disease. But I want to reserve judgment until we have done our study and have our own data."

The Cellular and Molecular Immunology Laboratory also is developing a test to assess dendritic cell function that could provide further information about the role of these cells in the context of immunodeficiencies.

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Tracy Will

Tracy Will is a senior marketing specialist at Mayo Clinic Laboratories where she covers innovation, specialty testing, and advances in laboratory medicine. Tracy has worked at Mayo Clinic since 2016.