If you have ever seen a Rheumatologist or there has ever been concern for lupus, you most likely have had your complement 3 (C3) and complement 4 (C4) tested. Unfortunately doctors do not do a great job of explaining these tests or their results, but are more often than not, considered when your doctor is assessing whether your lupus is “active” or “quiet.”
The complement system is complex and most doctors, aside from rheumatologists and immunologists, do not remember the specifics of the “complement cascade.” But you don’t need a PhD in immunology to have a basic understanding of how complements work and what they can teach us about our body.
What are complements?
Complements are simply proteins, found in our plasma, that are integral to our immune system’s health. When activated by the presence of foreign material in our system, they sound the alarm so bigger, badder immune cells can come to the rescue and destroy the offending material. There are different types of complements and when they work together they form a “complement cascade” that ultimately leads to a series of signals that alert immune cells such as macrophages and neutrophils. In this way, the complement system keeps us healthy and protected from various infections.
On occasion, however, the “foreign material” that activates the complement system, isn’t foreign at all and comes from our own body. The complement system isn’t specific for any particular foreign material, it simply acts in response to the presence of immune complexes (immune complexes are just big balls of antibodies attached to their antigen). Complements do not take into account whether the “foreign material” is actually foreign. And this is where we can get in trouble when we have an autoimmune condition.
Monitoring the C3 & C4 levels
Low complement levels are associated with a number of autoimmune conditions. Conditions such as vasculitis, antiphospholipid syndrome, sjogren’s syndrome, mixed cryoglobulinemia, hemolytic autoimmune anemia and glomerulonephritis can all have low complement levels. The most common condition, however, that we associate with low complements is lupus.
Lupus, immunologically speaking, is a condition of immune complex deposition and complement activation. (I know, lots of big medical words, but we’ll break it down!)
An immune complex is simply a complex of antibody and antigen. When an antibody recognizes another protein as “foreign” (even if incorrectly), a bunch of antibodies come and attach themselves to that protein, thus making an immune complex. The immune complex then goes and deposits on certain tissues or organs within the body. In the case of lupus, this can be the skin, the kidneys, the lungs, for example. It is still poorly understood why immune complexes deposit in one area and not another. The mere presence of that immune complex then triggers the complement cascade activation. As we described above, this cascade then calls all the immune cells to the area and results in inflammation. This inflammation then causes the symptom or organ damage that when then see.
Although there are 9 different types of complements, in practice the most commonly tested are C3 and C4. The C3 and C4 levels measured in the blood begin to fall as they get siphoned off to the tissues and organs, following the immune complexes. So in times of active lupus or lupus flares, blood testing of C3 and C4 will show low levels. This happens most readily in those with lupus kidney disease but can happen without kidney disease. Like most things rheumatology, however, nothing is 100%. In fact, this pattern, of low complements associated with a lupus flare is only present in ~50% of lupus patients. Following your own complement levels is one way you can get to know your “flavor” of lupus.
Get to know your complements
Whether you know it or not, if you have lupus, your doctor is likely checking your C3 and C4 levels each time you get blood drawn. And it is these results that can lead your doctor to say you “are fine” or not. But complement levels are most helpful when you see the result as part of the larger pattern. Here are some questions and points to review with your doctor to better understand your levels:
- What were your complement levels when you were first diagnosed with Lupus? Most people with lupus are diagnosed in the midst of a flare and knowing if your C3 and C4 levels were normal or low can be an important clue as to whether you are in the 50% of people with complement changes in flares or the other 50%.
- Do your complement levels change in accordance to how you feel? Do they go down when you feel bad and up when you are doing well? If so, then your levels are likely good markers of how your disease is doing. If not, or if only sometimes, then it can be trickier to interpret. Perhaps you are in the 50% where complements aren’t trustworthy markers? Or, perhaps your lupus is controlled, but your symptoms are related to another condition, such as fibromyalgia?
The intricacies and nuances of complement lab testing is something your Rheumatologist is best equipped to interpret. However, that does not mean you can’t get anything out of monitoring your own levels. With time and careful monitoring you can learn a lot about your body and condition.