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Updated on July 11, 2025
The immune system is a network of proteins, cells, tissues, organs, structures, and substances that fight infections. The immune system also helps the body fight off other diseases (such as destroying cancerous cells) and helps heal injuries.
While the immune system plays numerous critical roles in keeping a person healthy, excessive or abnormal immune system activity can damage healthy tissues and organs. One example is IgA nephropathy, a rare kidney disease characterized by inflammation and damage in the kidneys.
Here, we will look at how IgA nephropathy is associated with the activation of a part of the immune system called the complement system, and why the complement system can be an important therapeutic target in the treatment of IgA nephropathy.
What is IgA?
Antibodies are proteins that bind to foreign or harmful substances that have made their way into the body, such as viruses, infection-causing bacteria, and other pathogens. This binding process helps neutralize these substances and activates other parts of the immune system to respond.
Immunoglobulin A (IgA) is one of the main antibodies found in the human body. It’s found in mucous-producing cells, such as the inner linings of the respiratory and digestive tract. It is also found in fluids like blood, saliva, tears, and breast milk.
What is the complement system?
The complement system is a part of the immune system. It’s made up of dozens of proteins with specialized functions. These proteins activate in response to certain events or circumstances, such as the presence of a pathogen. Immunoglobulins (including IgA in some circumstances) play an important role in activating the complement system.
What is IgA nephropathy?
When a person has IgA nephropathy, the body makes abnormal IgA. This causes a chain of events that leads to the formation of immune complexes, clumps of IgA and other proteins. Immune complexes circulate in the blood and clog glomeruli. The glomeruli are the delicate filtering structures inside the kidneys that are made up of clusters of tiny blood vessels. Glomeruli are what enable the kidneys to remove excess fluid and waste from the bloodstream.
These deposits activate an inflammatory response by the complement system, which can cause significant damage to the glomeruli. Over time, this causes the formation of scar tissue and a permanent decline in kidney function. As a result, waste and excess fluid accumulate in the blood, while protein and blood cells end up in urine. This can lead to serious complications, including hypertension, heart failure, and edema. Kidney failure is another potential complication.
IgA can occur on its own or occur secondary to other health conditions, such as gastrointestinal disorders, liver disease, and autoimmune disorders.
What is the role of the complement system in IgA nephropathy?
While the exact cause of IgA nephropathy is not fully understood, research supports that it occurs as a result of a combination of genetic and environmental factors. Complement system activation is a continued topic of interest for medical researchers studying IgA nephropathy and investigating new ways to treat this disorder.
Activation of the complement system is the main cause of damage and loss of kidney function that occurs in IgA nephropathy. Drugs that regulate or reduce activity in the complement system are a new and emerging area of treatment for IgA nephropathy. These therapies can help slow the progression of damage to the kidneys.
Medications to control blood pressure, medications that reduce protein in the urine, corticosteroids, and diet/lifestyle changes to help protect the kidneys remain important parts of treating IgA nephropathy. For questions about treating IgA nephropathy or other types of kidney disease, your best source of information will be a healthcare provider.
