A biological marker is a molecule that indicates a particular state or process within a cell or an organism. These markers can signal the presence of a disease, how well the body responds to a treatment, or a normal biological function. CD38 is a significant protein marker found on the surface of various cells throughout the body. Its presence and activity are involved in numerous bodily functions.
The Basic Biology of CD38
CD38 is a protein embedded in the cell membrane, classified as a transmembrane glycoprotein. This molecule possesses multiple enzymatic activities, primarily functioning as an NADase and an ADPR cyclase. As an NADase, CD38 breaks down nicotinamide adenine dinucleotide (NAD+), a molecule crucial for cellular energy and various metabolic processes. Concurrently, its ADPR cyclase activity converts NAD+ into cyclic ADP-ribose (cADPR).
The cADPR produced by CD38 is a second messenger molecule that plays a fundamental role in regulating intracellular calcium signaling. Calcium ions are essential for numerous cellular functions, including muscle contraction, nerve impulse transmission, and hormone secretion. CD38’s ability to influence calcium levels means it impacts a wide range of cellular communication processes. This protein is widely expressed on diverse cell types, extending beyond just immune cells to include pancreatic islet cells, neurons, and prostatic epithelial cells.
CD38’s Involvement in Immune Regulation
CD38 is expressed on various immune cells, including T cells, B cells, natural killer (NK) cells, and macrophages. On T cells, CD38 can attach to CD31, leading to T cell activation and cytokine production. CD38 also influences B cell activation by regulating their receptor signaling.
Innate immune cells like macrophages express CD38, where it regulates cytokine release, adhesion, and cellular migration towards sites of inflammation. CD38 contributes to the activation and migration of myeloid immune cells in inflammatory processes. Its activity helps regulate inflammation, influencing immune cell recruitment and function. CD38 impacts both innate and adaptive immunity.
CD38 in Disease Development
Dysregulation of CD38 contributes to the development and progression of several diseases. In cancers like multiple myeloma and chronic lymphocytic leukemia (CLL), CD38 is often highly expressed on malignant cells. In multiple myeloma, this high expression makes CD38 a target for therapies, as it is uniformly present on myeloma cells. For patients with B-cell chronic lymphocytic leukemia, increased CD38 expression is associated with a more aggressive disease and shorter survival times.
CD38 also contributes to chronic inflammatory conditions. For instance, in individuals with HIV, persistent high CD38 expression on T cells is linked to chronic inflammation, even when the viral load is controlled by medication. The enzymatic activity of CD38 can also promote the migration and proliferation of cancer cells in some solid tumors, such as ovarian and lung cancer.
Clinical Relevance of CD38
CD38 has applications in clinical settings, particularly in diagnosing and treating certain diseases. As a diagnostic biomarker, CD38 expression levels provide information for prognosis and monitoring disease activity in specific leukemias and lymphomas. For example, measuring CD38 on chronic lymphocytic leukemia cells helps identify patients with more aggressive forms of the disease. It also assists in classifying certain hematological malignancies.
Beyond diagnosis, CD38 is a therapeutic target, especially in oncology. Monoclonal antibodies, such as daratumumab, have been developed to specifically bind to and block CD38 on cancer cells. These therapies lead to the destruction of CD38-expressing cells. These treatments improve the management of diseases like multiple myeloma by directly eliminating malignant cells and modulating the immune environment.