There are over 300 known primary immunodeficiency diseases (PIDDs) and that number continues to grow. Making a definitive diagnosis can present quite a challenge and requires using multiple testing modalities—an intimidating prospect especially given the increasingly prominent role of molecular testing.

The good news for 2020 AACC Annual Scientific Meeting attendees is that this session, “Evaluating Primary Immunodeficiencies: An Example of Integrating Genetic and Functional Testing,” on Monday, December 14 at 2:00 pm Central, aims to outline effective tactics to combine molecular, serologic, and cellular assays to reach a diagnosis. As speaker Attila Kumanovics, MD, points out, by using multiple testing methods, the assays “can complement each other’s blind spots if interpreted together.”

PIDDs fall into several broad categories: B-cell/antibody deficiencies, T-cell deficiencies, combined B- and T-cell deficiencies, complement deficiencies, phagocyte disorders, and idiopathic disorders. Accurate diagnosis is essential for appropriate treatment, which ranges from pharmacotherapy, biologics, bone marrow transplant, or gene therapy, depending on the specific PIDD. While PIDDs individually are quite rare, as a group they affect a significant number of people.

Kumanovics illustrates that PIDDs might impact people in more common ways than previously expected: “Recent studies suggest that 3-4% of severe COVID-19 pneumonia cases may have an underlying monogenic cause, reflecting a possible immunodeficiency.” He explains that this COVID-19 observation might indicate that PIDDs are more common than previously thought and that they might manifest later in life. This is one of many reasons why it is important to recognize and diagnose immunodeficiencies.

Speaker Ann Moyer, MD, PhD, notes that despite the different categories of PIDDs, “From a genetic standpoint, these disorders are interesting in part because they can result from multiple inheritance patterns. New causative genes are being identified regularly, and some of the important variants and genes can be difficult to test by next-generation sequencing.”

This underscores the need for multiple avenues of testing to reach a diagnosis. She plans to share her experiences with creating and validating assays for PIDDs to help others do the same in their own labs. Moreover, she notes that while this session is on PIDDs, the lessons being shared apply to many kinds of disorders.

“Our main message is that a diagnostic approach that combines functional and genetic testing is the best … because there are benefits and limitations to each approach when used independently,” Moyer says.

Integrating multiple testing modalities can benefit numerous areas of medicine, including immunology. This session shows attendees the molecular, serological, and functional assays that can be interpreted together to diagnose PIDDs.