Laboratory Markers for Lupus Flares

Are there any objective lab markers that can be checked when a flare of lupus is suspected? Are there any markers correlating with disease severity and progression in patients with lupus? I have found that checking the following blood tests can be helpful in my patients with lupus.

Double-stranded DNA antibody titer

The double-stranded DNA antibody level not only aids and solidifies the diagnosis of systemic lupus erythematosus. It is 1 of the only antibodies that fluctuate up and down with lupus flares and disease activity levels. This is in contrast to the ANA titer and other tests, like the anti-Smith antibodies, which can help with lupus diagnosis but do not trend up or down with flares. In my patients with severe manifestations of lupus and frequent flares, I monitor their double-stranded DNA antibody levels periodically. These tend to correlate with their flares and can reflect how well they are responding to treatments.^1,2

Erythrocyte sedimentation rate (ESR)

The erythrocyte sedimentation rate, more commonly referred to as ESR or a "sed rate," is used frequently to monitor inflammation in multiple conditions, including lupus. Using ESR to predict systemic inflammation and flares has positive and negative aspects. The positive is that the ESR is quite sensitive for detecting inflammation and can be 1 of the early markers of lupus flares when other markers are still normal.³

The downfall of the ESR test is that it's not very specific for lupus or autoimmune diseases. The test measures how fast a person's red blood cells fall within a test tube – hence the name. Conditions like anemia can affect the test results and falsely elevate the ESR level. This marker can also be elevated in conditions such as infection, cancer, diabetes, severe obesity, or just regular aging. In fact, some experts say that the ESR level should be adjusted for a patient's age since it tends to rise as we age.^4,5

C-reactive protein (CRP)

Compared to the ESR level, the CRP test is a newer inflammation marker with greater specificity for inflammatory conditions and flares. It more accurately reflects a state of systemic inflammation and is not affected by conditions such as anemia. Some conditions, such as infection, cancer, and severe obesity, can still cause a mild elevation in the CRP level.⁴

A challenge occurs when the ESR and CRP levels don't match up – which happens quite often. It is difficult to interpret results when ESR is elevated but CRP is normal, or vice versa. It can also be difficult to tell from these markers whether a patient is experiencing a flare of lupus or just going through something like the cold or flu, which are infections that can cause inflammatory markers to rise. I usually take both the ESR and CRP with a grain of salt and try to correlate them with clinical findings of lupus flares, such as joint pain, swelling, or skin rashes.^5,6

Complement levels

Another tool to assess a lupus flare is the measurement of complement levels. Complement levels affect our immune system's ability to fight bacteria and viruses. There are 2 complement levels – C3 and C4 – which drop to low levels during a lupus flare. This is because the complements are being deposited in organs, so they are found less abundantly in the blood. Low complement levels indicate that patient may be experiencing a flare of lupus and has an active ongoing disease process. Normal complement levels may indicate that lupus is well-controlled or in a period of remission. High complement levels are usually a normal variant and usually do not indicate that lupus is flaring or active.^7,8

Have you had any of these tests? What did your doctor tell you about them, or about your results?