CD11a is a protein found on the surface of immune cells. It mediates how these cells interact with other cells and tissues. Its function is significant in orchestrating immune responses, contributing to both protective immunity and, when dysregulated, to certain health conditions.
CD11a’s Role in Immune Function
CD11a is a subunit of Leukocyte Function-associated Antigen-1 (LFA-1). LFA-1 is an integrin composed of two parts: the CD11a subunit (alpha L) and the CD18 subunit (beta 2). This LFA-1 complex is expressed on the surface of all leukocytes.
LFA-1 enables immune cells to adhere to other cells and tissues. It binds to specific partners like intercellular adhesion molecules 1-3 (ICAM-1, ICAM-2, ICAM-3). These ICAMs are often found on the surface of endothelial cells and antigen-presenting cells.
This binding facilitates several immune processes. It allows immune cells to migrate from the bloodstream into inflamed tissues, a process known as diapedesis or extravasation. This interaction also contributes to the activation of immune cells, particularly T-cells, and the formation of the immunological synapse. The immunological synapse is a specialized junction between a T-cell and an antigen-presenting cell, necessary for effective immune activation and signal transduction.
CD11a and Its Impact on Health
Dysregulated CD11a function can contribute to health issues, particularly inflammation. Excessive or inappropriate adhesion mediated by CD11a can lead to chronic inflammatory responses. This dysregulation means immune cells might accumulate in tissues where they are not needed, causing ongoing damage.
CD11a’s aberrant activity is also implicated in several autoimmune diseases. In conditions like psoriasis, overactive T-cells, facilitated by CD11a, contribute to skin inflammation. Similarly, in multiple sclerosis and rheumatoid arthritis, abnormal CD11a function can lead to immune cells targeting and damaging nerve tissue or joint linings, respectively.
CD11a also contributes to transplant rejection. Following an organ transplant, the recipient’s immune system recognizes the new organ as foreign. CD11a on the recipient’s immune cells facilitates their recognition and attack of transplanted tissues, leading to rejection. Modulating CD11a activity is therefore a focus in preventing this immune response.
Targeting CD11a for Treatment
CD11a’s role in immune cell interactions makes it a target for therapies, especially where immune overactivity is a problem. One approach uses therapeutic antibodies to block CD11a and LFA-1 activity. These antibodies aim to prevent immune cells from adhering and migrating to sites of inflammation.
Efalizumab (Raptiva) was a notable example. This humanized monoclonal antibody bound specifically to the CD11a subunit of LFA-1. It inhibited LFA-1 binding to its ligand, ICAM-1, preventing T-cell activation and migration.
Efalizumab was approved for moderate to severe plaque psoriasis. It was administered as a once-weekly subcutaneous injection. It aimed to reduce activated T-cells in the skin, improving psoriasis symptoms.
However, efalizumab was voluntarily withdrawn from the market in 2009 due to serious safety concerns. The primary reason for its withdrawal was the risk of progressive multifocal leukoencephalopathy (PML), a rare but severe brain infection caused by the JC virus. PML affects individuals with weakened immune systems, potentially leading to severe disability or death. Several cases of PML were reported in patients treated with efalizumab, with an incidence of approximately one in 500 treated patients. This risk, particularly with longer treatment duration, led regulatory bodies like the FDA and European Medicines Agency to recommend its suspension.