The Role of CD38 Activity in the Impaired Immune Response

Cluster of differentiation 38 (CD38) is a multifaceted protein contributing to immune response, cell adhesion, and signal transduction. Furthermore, it plays a vital role in calcium signaling, which is necessary for further cell signaling. Calcium acts as a second messenger regulating muscle contraction, cell growth, fertilization, and cellular motility, to name a few areas of relevance.

Calcium levels are increased in patients with multiple myeloma (MM). MM is a type of cancer that affects plasma (white blood) cells, ultimately affecting antibody production.¹ Additionally, asthma can result from calcium levels not being appropriately regulated.² This inflammatory disease affects millions putting a massive burden on our healthcare system.

Inflammation and antibody production are essential in the immune response, allowing our bodies to fight and eliminate disease, allergies, and injuries. The inflammatory response recruits several mediators, such as cytokines, to aid in the destruction of foreign molecules invading the body. CD38 acts as a receptor to activate numerous cytokines that are involved in the immune response.²

In the case of MM, scientists have found multiple inhibitors against CD38 which eliminate tumor cells.¹ Although this is the case, there’s always room for improved therapies, especially since relapse is common.

Calcium Signaling Pathway

Calcium levels are typically at a resting level in the cell’s cytoplasm, and to remain at that level there is a regular release into the extracellular space. However, there are times when calcium is released in more significant amounts. One example is when CD38 is activated. CD38 has enzymatic activity that drives second messengers to regulate calcium levels. Specifically, as tumor necrosis factor (TNF) enhances CD38 in airway smooth muscle (ASM) cells, cyclic ADP-ribose (cADPR) releases calcium which increases the dysfunctional contractility in asthma. ²   Finding ways to control CD38 will ultimately lead to solutions for patients who have asthma.

CD38 Enzymatic Activity Assay 

As researchers continue to find molecules capable of inhibiting CD38 to combat a plethora of illnesses, including cancer and inflammatory-related diseases, there are ever-growing technological advances that assist this research.  Transcreener Assays are capable of detecting enzymatic activity, of Kinases, ATPases, and various other proteins. These biochemical assays are capable of testing multiple targets due to their flexible design which is ideal for drug discovery. Other ways these assays can assist in research in the fight against diseases that are due to an impaired immune response are as follows:

• Determine enzymatic activity
• Screen for small molecule inhibitors
• Profile inhibitor potency / determine IC₅₀ values
• Mechanism of action studies

Learn more about how the Transcreener Assay was developed to measure CD38.

Learn More About the CD38 Assay

References

1. Petrucci, M. T., & Vozella, F. (2019). The Anti-CD38 Antibody Therapy in Multiple Myeloma. Cells, 8(12), 1–9. https://doi.org/10.3390/cells8121629
2. Glaría, E., & Valledor, A. F. (2020). Roles of CD38 in the Immune Response to Infection. Cells, 9(1). https://doi.org/10.3390/cells9010228
3. Guedes, A. G. P., Deshpande, D. A., Dileepan, M., Walseth, T. F., Panettieri, R. A., Subramanian, S., & Kannan, M. S. (2014). CD38 and airway hyper-responsiveness: Studies on human airway smooth muscle cells and mouse models. Canadian Journal of Physiology and Pharmacology, 93(2), 145–153. https://doi.org/10.1139/cjpp-2014-0410