CD55, also known as Decay-Accelerating Factor (DAF), is a protein found on the surface of human cells. It acts like a protective shield, signaling to the immune system that the cell belongs to the body. This helps prevent the immune system from mistakenly attacking healthy cells.
The Function of CD55 in the Complement System
The human body possesses an intricate defense mechanism known as the complement system, a part of the innate immune system. This system consists of proteins that work in a cascade to identify and eliminate invading pathogens like bacteria and viruses. When activated, these proteins can coat pathogens, making them easier for immune cells to clear, or directly punch holes in their membranes, leading to destruction.
CD55 plays a specialized role in regulating this powerful system, preventing it from damaging the body’s own healthy cells. Its alternative name, Decay-Accelerating Factor, describes its function: it accelerates the breakdown of protein complexes called C3 and C5 convertases. By destabilizing these convertases, CD55 limits the amplification of the complement response on cell surfaces. This ensures the complement system targets only foreign invaders, leaving host cells unharmed.
Consequences of CD55 Deficiency
When CD55 is absent or not functioning correctly, the body’s own cells become vulnerable to attack by the unregulated complement system. A primary example of this vulnerability is Paroxysmal Nocturnal Hemoglobinuria (PNH), a rare acquired blood disorder. In PNH, a mutation in the PIGA gene prevents the proper formation of a glycophosphatidylinositol (GPI) anchor, which is necessary for CD55 and another protective protein, CD59, to attach to cell surfaces.
The absence of these GPI-anchored proteins, particularly CD55 and CD59, on red blood cells makes them highly susceptible to destruction by the complement system. Without CD55 to dismantle the C3 convertases, the complement cascade proceeds unchecked on the red blood cell surface, leading to the formation of a “membrane attack complex” (MAC). This complex causes them to burst, a process known as intravascular hemolysis. Patients with PNH often experience symptoms such as anemia, fatigue, and dark-colored urine due to this ongoing red blood cell destruction.
CD55’s Role in Cancer and Infection
Beyond its role in preventing complement deficiency, CD55 is also implicated in other disease processes. In various cancers, tumor cells can overexpress CD55 on their surface. This overexpression acts as a protective mechanism, shielding cancer cells from destruction by the immune system, particularly from complement-mediated attacks. By maintaining high levels of CD55, cancer cells effectively evade immune surveillance.
CD55 also serves as a binding site for certain pathogens, allowing them to gain entry into host cells. Several enteroviruses, such as echoviruses, and certain bacteria like uropathogenic Escherichia coli, utilize CD55 as a receptor. This interaction facilitates the pathogen’s adhesion to and invasion of human cells, contributing to chronic infections. For instance, the malaria parasite Plasmodium falciparum has been shown to use CD55 as an essential host receptor for infection.
Medical Testing and Therapeutic Approaches
Diagnosing conditions related to CD55 deficiency, such as PNH, primarily relies on a specialized laboratory test called flow cytometry. This technique can precisely measure the presence or absence of specific proteins like CD55 and CD59 on the surface of blood cells. A blood sample is taken, and cells are mixed with fluorescently labeled antibodies that bind to these proteins; the flow cytometer then detects the fluorescence, indicating whether the proteins are present. Detecting the absence or reduced expression of both CD55 and CD59 on red blood cells and granulocytes is diagnostic for PNH.
Therapeutic strategies for conditions like PNH aim to counteract the effects of missing CD55. Complement inhibitors are drugs designed to block specific components of the complement system. For example, drugs such as eculizumab and ravulizumab target the C5 protein in the complement cascade, preventing the formation of the membrane attack complex and reducing intravascular hemolysis. Newer inhibitors target earlier points in the complement pathway, such as C3 or Factor D, for broader protection.