Lupus Lab Tests Explained: What Blood Tests Mean for Diagnosing and Monitoring Lupus

Understanding your lupus lab tests when you have lupus can be overwhelming. Labs such as ANA, anti-dsDNA, and complement levels are essential for diagnosing lupus, measuring disease activity, and guiding treatment decisions. Most patients can now view their lab results easily online. It is common to see many abnormal results that are not important (clinically unimportant). Always ask your doctor what they mean in your case. However, it is helpful for you to know the results of some of these labs so you can take better care of your lupus.

---

NOTE: Johns Hopkins University Press, publisher of The Lupus Encyclopedia, is a nonprofit publisher. If you purchase JHUP books, like The Lupus Encyclopedia, you support projects like Project MUSE.

---

In this article, I will explain some of the most commonly used tests. These descriptions come directly from a draft write-up for my 3rd edition of “The Lupus Encyclopedia” (Concise edition). In the 2nd edition, I list all the essential labs done in lupus (this is a short list). All you have to do is look up your lab test name in the index and easily find a complete description. The 2nd edition goes into more detail than below. Click on the link above.

Basic Blood and Urine Lupus Lab Tests

Complete Blood Count (CBC)

There are three major blood cell components: white blood cells, red blood cells, and platelets (see chapter 8). I list only the most essential tests in SLE.

White Blood Cells (WBCs). Also called “leukocytes.” The WBC count includes all white blood cells. The CBC also measures different types of WBCs—neutrophils (called granulocytes), lymphocytes, monocytes, basophils, and eosinophils. The first two are more important in SLE. A low WBC is called leukopenia.

Possible causes of an elevated WBC (leukocytosis) include prednisone, infection, stress, inflammation, or blood cell cancers.

Hemoglobin (HGB, or Hb). Hb is an RBC protein that carries oxygen. Low Hb or Hct is called “anemia” (chapter 8). High Hb or Hct is commonly seen in smokers. Other causes of high levels are rare.

Hematocrit (HCT, “crit”). See Hb above.

Mean Corpuscular Volume (MCV). MCV measures the average RBC size. It helps narrow down the causes of anemia. Low MCV may be due to iron deficiency, thalassemia (an inherited anemia), or sickle cell disease, among other causes. High MCV may be due to autoimmune hemolytic anemia, vitamin B12 or folic acid deficiency, liver disease, medications, or excessive alcohol.

Platelet Count. Also called thrombocytes. Essential for forming blood clots that prevent bleeding. SLE can cause low platelets (thrombocytopenia). High platelet counts (thrombocytosis) may be due to infection, inflammation, or iron-deficiency anemia.

Basophils (Absolute Basophil Count). Basophils participate in allergies and infections. It can be low during active SLE. If basophils increase during treatment, this can signify successful treatment. High basophils may be due to inflammation, infection, hypothyroidism, or leukemia.

Lymphocytes (Absolute Lymphocyte Count, ALC). Made up of B lymphocytes and T lymphocytes (called B cells and T cells). They identify foreign invaders by recognizing their foreign proteins (antigens) and alerting the immune system. B cells produce antibodies, which identify and help eliminate foreign substances. B cells produce lupus autoantibodies, such as antinuclear antibodies, anti-DNA antibodies, and anti-Smith antibodies.

Low lymphocytes (lymphopenia or lymphocytopenia) can occur during active SLE or from steroids (like prednisone). Increased lymphocytes can be seen from infections, inflammation, or, rarely, blood cancers.

Neutrophils (Absolute Neutrophil Count, ANC). WBCs that fight infections. Low levels (neutropenia) can be due to active SLE or from medications. High levels can occur from steroids, infections, inflammation, or rarely, blood cancers.

Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)

Erythrocyte Sedimentation Rate (Sedimentation Rate, Sed Rate; ESR, Westergren). High levels may be due to anemia, obesity, older age, being female, pregnancy, and other causes of inflammation (such as infections). See CRP regarding infections and other lupus problems.

C-Reactive Protein (CRP). Elevated CRP can be due to inflammation, obesity, or a high level can indicate you have an increased risk for heart attacks, strokes, and hardening of the arteries.

CRP and ESR (see below) tend to be higher in infections than in active SLE. However, lupus aortitis (vasculitis of the aorta), pleuritis (pleurisy), and pericarditis can also cause very high levels.

Antinuclear Antibody (ANA) Test

Antinuclear Antibody (ANA, FANA). ANA is positive in almost everyone with SLE. It is rarely negative in newly diagnosed patients with SLE when evaluated by the immunofluorescence assay (IFA), the “gold standard” for screening for SLE. 95% of newly diagnosed SLE patients are positive for IFA ANA.

Some newly diagnosed SLE patients may be ANA-negative by IFA but positive by another method (such as ELISA; see below), or may have antibodies like anti-dsDNA or anti-SSA, or may have SLE due to a genetic deficiency in complement levels.

Up to 20% of healthy people test positive for ANA, while up to 37% of those older than 65 do.

ANA can be positive in other autoimmune disorders, infection, cancer, medications, and any cause of inflammation. When someone is ANA-positive, it is essential to conduct additional tests, including other autoantibodies (such as anti-Smith for lupus and anti-Scl-70 for scleroderma).

Several other methods test for ANA. The first group is “solid phase immunoassays,” including the multiplex immunoassay and the enzyme-linked immunosorbent assay (ELISA). These are ordered most often because they are relatively cheap.

IFA ANA contains around 150 antigens (types of proteins) that ANA can bind to. The multiplex immunoassays detect only about 10—up to 35% of people with SLE test negative.

If someone is negative for IFA ANA and SLE is suspected, a multiplex ANA immunoassay should be performed. IFA ANA can be negative, while solid-phase ANA can be positive in some SLE patients.

ANA by IFA is measured in titers. Most labs consider a titer of 1:40 or 1:80 and higher to be a positive ANA. The higher the titer, the greater the risk of autoimmune diseases such as SLE.

ANA by IFA produces different appearances, or patterns, on the microscope slide. The two most common in SLE are diffuse (also called homogenous) and speckled. However, they are also the most common in healthy ANA-positive people. Therefore, these patterns are not helpful.

Nuclear-dense, fine-speckled pattern ANA should be tested for anti-DFS70 antibodies. Someone positive for anti-DFS70 but negative for other autoantibodies (such as anti-dsDNA, anti-Smith, anti-SSA, and others) is less likely to have SLE.

A nucleolar pattern is more common in people with scleroderma (also called systemic sclerosis), but it can also be seen in SLE and myositis.

The centromere pattern is due to centromere antibodies (see centromere antibody, below).

ANA levels do not reliably fluctuate with disease activity. ANA becomes negative in 20-30% of well-treated patients. SLE patients who become ANA-negative are less likely to flare than those who are persistently positive.

ANA-negative SLE. Potential causes of a negative ANA in SLE patients include well-controlled SLE, variations in laboratory quality, intermittent ANA positivity, autoantibodies directed against antigens outside the nucleus, antibodies to antigens expressed only during cell division, and low immunoglobulin levels (described below). Around 37% of cutaneous lupus patients who do not have systemic involvement are ANA-negative.

Also see lupusencyclopedia.com/ana-positive-how-to-get-a-lupus-diagnosis

Anti-dsDNA 

dsDNA Antibody (Anti-dsDNA Antibody, Anti-Double-Stranded DNA Antibody, DNA (DS) AB, Anti-Native DNA). Antibodies against dsDNA appear in up to 80% of SLE patients and are uncommon in people without SLE. However, it can occasionally be seen in other systemic autoimmune diseases (especially Sjögren’s disease and drug-induced lupus).

Anti-dsDNA can help monitor treatment. Anti-dsDNA may rise during periods of lupus activity and decline when lupus activity improves. A progressively increasing anti-dsDNA level might signal a potential flare in patients who otherwise appear to be doing well, especially if it is accompanied by a decreasing C3 or C4 level or an increasing EC4d. However, many SLE patients have elevated anti-dsDNA levels that do not fluctuate with disease activity.

Anti-dsDNA SLE patients are at increased risk of lupus nephritis and vasculitis (inflammation of blood vessels). This does not mean that they will develop either. Instead, a positive result tells the doctor to pay closer attention to these possibilities.

There are several methods for measuring anti-dsDNA antibodies: ELISA (discussed earlier in the ANA section), the Farr assay, chemiluminescence immunoassay (CIA), and the Crithidia luciliae immunofluorescence assay.

The Crithidia test is one of the most specific tests for SLE; it is rarely positive in people without SLE. However, it can miss many people with SLE (i.e., it is often negative in SLE, whereas another anti-dsDNA method may be positive).

Patients vary widely in which anti-dsDNA methods they are positive for, and which method most reliably reflects their lupus disease activity.

Anti-dsDNA antibodies can occur in drug-induced lupus from minocycline, propylthiouracil, quinidine, and tumor necrosis factor inhibitors (such as adalimumab [Humira], etanercept [Enbrel], and infliximab [Remicade]).

Anti-Chromatin Antibody

See my blog post on chromatin antibody: https://www.lupusencyclopedia.com/chromatin-antibodies/

Anti-Smith (Anti-Sm), Anti-RNP Antibodies

Smith Antibody (Anti-Smith Antibody, Anti-Sm, Sm Antibody). Present in up to 40% of SLE patients. If anti-Sm is positive, anti-RNP is almost always positive. Anti-Smith rarely occurs in individuals without SLE. It helps diagnose SLE but does not help monitor disease activity.

It is more common in people of African ancestry. It increases the risk for pleurisy, nephritis (kidney inflammation), psychosis, seizures, lung disease, low white blood cell counts, arthritis, discoid rash, butterfly rash, vasculitis, pulmonary hypertension, mouth sores, and worse overall disease.

RNP Antibody (Anti-Ribonucleic Protein, Anti-RNP, Anti-Mo, U1RNP antibody). This is not to be confused with anti-U3RNP (seen in myositis). Anti-RNP antibodies are present in up to 60% of SLE patients and increase the risk of swallowing problems, muscle inflammation, Raynaud’s phenomenon, lung inflammation, pulmonary hypertension, brain inflammation, low white blood cell counts, and arthritis.

RNP antibodies also appear in rheumatoid arthritis, Raynaud’s phenomenon, Sjögren’s, and scleroderma. It is most helpful in diagnosing mixed connective tissue disease (MCTD). MCTD patients always have high anti-U1-RNP antibodies (especially anti-RNP-70kDa). RNP antibodies can be further divided into IgM and IgG forms. Patients with SLE are more likely to have high IgM levels; IgG is more common in MCTD.

RNP antibodies can remain positive for many years before the development of an autoimmune disease. Healthy anti-RNP-positive people should be monitored regularly. Relatives of patients with SLE who are anti-RNP positive are more likely to develop SLE than those who are not. Also see lupusencyclopedia.com/uctd

Anti-Ro/SSA and Anti-La/SSB Antibodies

SSA (Anti-Sjögren’s Disease A, Sjögren’s Anti-SS-A, Anti-SSA, Ro Antibody). Anti-SSA is the same as anti-Ro; anti-SSB is the same as anti-La.

Up to 75% of people with Sjögren’s disease are anti-SSA-positive, but it can also occur in other systemic autoimmune diseases, cancer, and infections.

Depending on the study, anti-SSA occurs in 20% to 60% of SLE patients, increasing the risk of sun-sensitive rash (especially subacute cutaneous lupus), lung inflammation, shrinking lung syndrome, liver inflammation, pancreatic inflammation, heart inflammation, low platelet counts, low lymphocyte counts, and an overlap syndrome with Sjögren’s.

Some ANA-negative SLE patients are anti-SSA-positive.

Anti-SSA can appear many years before SLE or Sjögren’s. Anti-SSA-positive healthy people should be monitored regularly. However, some anti-SSA-positive people never develop any disease.

Anti-SSA can cause neonatal lupus

SSB (Anti-Sjögren’s Disease B, Sjögren’s Anti-SS-B, Anti-SSB, La Antibody, Ha Antibody).

Anti-SSB occurs in up to 25% of people with SLE and up to 60% of people with Sjögren’s, but can be present in other systemic autoimmune diseases, cancer, or infection. People with SLE who are positive for both anti-SSA and anti-SSB antibodies have a higher risk of subacute cutaneous lupus, sun sensitivity, heart inflammation, and seizures, but are less likely to develop lupus nephritis.   It is unusual to be positive for anti-SSB without being positive for anti-SSA (called isolated anti-SSB), but this can occur. Isolated anti-SSB positivity (anti-SSA-negative) doesn’t increase the risk for Sjögren’s. Also see lupusencyclopedia.com/know-your-lupus-labs-anti-ssa

Urinalysis and Urine Protein Results

Urinalysis

The urinalysis helps identify lupus nephritis (kidney inflammation), which occurs in around 45% of SLE patients. Urinary tract infections, diabetes, kidney stones, drug side effects, or kidney/bladder cancer can also be found.

Urine Protein-to-Creatinine Ratio (UPCR, Protein/G Creat, Protein/Creat Ratio)

What It Looks For: One of the most valuable tests for SLE. The protein concentration (labeled as protein, urine) and creatinine concentration (labeled as creatinine, urine) appear separately on the lab slip. These values are not helpful on their own. Pay attention to only the UPCR (the protein level divided by the creatinine level).

Elevated UPCR can be due to lupus nephritis, RBCs, medications, other kidney diseases, kidney damage, sitting or standing (if collected after the 2nd void of the day), or other body proteins (such as immunoglobulins, myoglobin, and hemoglobin).

If the UPCR is elevated, your doctor may order a 24-hour urine collection or even a kidney biopsy to see if there is evidence of lupus nephritis. Almost everyone with active lupus nephritis has elevated urinary protein.

Complement Levels (C3, C4)

Complement C3 (C3, Complement Component C3). The immune systems of most people with SLE will use up C3 and C4 during immune activation. This can cause C3 and C4 blood levels to decrease. In someone whose C3 or C4 consistently drops during disease flares and improves during disease control, it can help monitor their SLE.

In most people with lupus, C3 and C4 do not change much with disease activity. A cell-bound complement activation product, EC4d (discussed later), may be more helpful in these individuals.

In patients who appear well, progressively decreasing C3 or C4 levels may signal an impending flare, especially if accompanied by rising anti-dsDNA.

Low C3 and C4 levels can also be seen in IgG4-related disease.

High C3 or C4 can increase during nonspecific inflammation and should increase during pregnancy. If levels do not rise in pregnancy, this may indicate active SLE and an increased risk for pregnancy complications.

Antiphospholipid Antibody Panel

Cardiolipin Antibodies (Anticardiolipin Antibodies, ACLA). Cardiolipin antibodies are a type of antiphospholipid antibody (aPLA). aPLAs are present in up to 55% of people with SLE and include ACLA, lupus anticoagulant, and beta-2-glycoprotein-1 antibodies.

Approximately 50% of SLE patients with aPLAs may get blood clots or have recurrent miscarriages; this is called antiphospholipid syndrome (APS).

See lupusencyclopedia.com/anticardiolipin-antibodies-and-lupus

Lupus Anticoagulant (Dilute Russell’s Viper Venom Test, PTT-LA with Reflex to Hexagonal Phase Return, dRVVT with Mixing Study, LAC, dRVVT, Kaolin Clot Time). LAC is one of the antiphospholipid antibodies (see Cardiolipin Antibody).

Approximately 30% of people with SLE are LAC-positive, and roughly half of them may develop blood clots.

ß-2 Glycoprotein I Antibodies (Beta-2 Glycoprotein I Antibodies, Anti-ß-2 Glycoprotein I, and ß-2 GPI). Beta-2 GPI (ß is the Greek letter “beta”) is one of the antiphospholipid antibodies

Vitamin D Levels

Vitamin D, 25-Hydroxy (Calcidiol, 25-Hydroxycalciferol, 25-OH-D). The most helpful test for diagnosing and monitoring vitamin D. I aim for a level of 40 to 59 ng/mL to help lupus disease activity.

Thyroid Function Tests

Thyroid-Stimulating Hormone (Thyrotropin; TSH, 3rd Generation). Produced in the brain and directs the thyroid gland (located under the Adam’s apple region in the neck) to release thyroid hormones. TSH is the most helpful test in detecting abnormal thyroid hormone production. High TSH indicates an underactive thyroid gland (hypothyroidism); low TSH indicates an overactive thyroid (hyperthyroidism) or can occur from steroids.

Thyroid Peroxidase Antibody (AbTPO, Microsomal antibody, Thyroperoxidase Antibody, TPO Antibody, TPOAb). Thyroid peroxidase antibody appears in especially high levels in Hashimoto’s thyroiditis. It can also occur in other thyroid diseases like Graves’ disease. Up to 40% of SLE patients are AbTPO-positive, and one-third of SLE patients also have autoimmune thyroid disease.

What to Do if your Lab Tests are Abnormal

Look them up on this blog post. If they are not there, consider getting a copy of the 2nd edition of The Lupus Encyclopedia, look them up in the index. You will find full explanations. Then if you are still unsure of their meaning, ask your doctor.

How Often Should Lupus Labs be Checked?

I like to check labs, especially the urine protein:creatinine ratio. This helps identify patients with early, mild lupus nephritis at a stage that is most easily treated and brought into remission.

Monitoring Lupus Over Time

Some tests are very important in monitoring how well lupus responds to treatment and to see if any organ systems are active or not.

Labs that can fluctuate with disease activity:

Anti-dsDNA, anti-C1q, C3, C4, EC4d, quantitative immunoglobulin levels.

There is recent evidence that in some patients, anti-Smith and anti-RNP may also help follow disease activity.

Summary and Key Take-Aways

Labs are vital for diagnosing and monitoring our SLE patients. However, they are just one piece of the puzzle. Empower yourself. Look up your results in patient resources, such as this blog post and the 2nd edition of The Lupus Encyclopedia. However, every SLE patient is different, and a particular result in one patient may mean something very different in another. Always check with your doctor.

For more in-depth information on Lupus Lab Tests Explained: What Blood Tests Mean for Diagnosing and Monitoring Lupus:

Read more in The Lupus Encyclopedia, edition 2

Look up your symptoms, conditions, and medications in the Index of The Lupus Encyclopedia

If you enjoy the information from The Lupus Encyclopedia, please click the “SUPPORT” button at the top of the page to learn how you can help. 

---

What are your comments and opinions?

If you have lupus, what has your experience been? What do you recommend for other patients?

Do you have any questions to ask Dr. Thomas?

Please click on “Leave a Comment” above to comment.

Please support “The Lupus Encyclopedia” blog post page

Click on “SUPPORT” at the top of the page to learn how you can support “The Lupus Encyclopedia“

FAQs

This article includes contributions from