Lupus in the Lab

*Disclaimer:

Interpretation of test results varies depending on the patient. Please consult a physician or other healthcare professional with a complete understanding of the clinical context for the most accurate interpretation.

*There is no single test that can diagnose lupus. A combination of the following tests, as well as signs and symptoms and physical examination helps doctors diagnose lupus.

*SLE=systemic lupus erythematosus.

*Blood tests are listed in alphabetical order.

Sensitivity— the ability of a test to correctly identify people with a disease. A highly sensitive test means that there are few false negative results. If the test came back negative, you can be confident you do not have the disease.

If it is unlikely that you have SLE, doctors will run a sensitive test to rule out the

possibility, such as ANA.

Specificity— the ability of a test to correctly identify people without a disease. A highly specific test means that there are few false positive results. If the test came back positive, you can be confident that you have the disease.

If it is very likely that you have SLE, doctors will run a specific test to confirm the disease, such as anti-dsDNA or anti-Sm.

See a word you don't understand? Find it in our glossary.

Your immune system produces antibodies to attack bacteria and viruses. In SLE, your body produces malfunctioning antibodies (autoantibodies, auto for “self”) that attack your own, normal cells. This test tests for the presence of antinuclear antibodies, antibodies that act against the nuclei of your cells.

This test is not specific for SLE, meaning a positive test does not always mean you have SLE.

ANA is a 2-part test, usually reported as titers and patterns.

Titers— the number of times a blood sample can be diluted before the antibodies can no longer be detected.

• Titers are usually expressed as ratios, such as 1:160 (1 part serum to 160 parts dilutant results in no antibodies remaining detectable in the sample). Therefore, the higher the titer, the more likely an autoimmune disease exists.

• Titer must be greater than 1:80 to be positive (e.g., 1:160, 1:320, 1:640).

Pattern— describes where on the nucleus the autoantibody attacks and gives information about the type of autoimmune disease.

• Homogenous (diffuse) pattern: common in people with SLE

• Speckled pattern: common in people with SLE

• Peripheral pattern: almost exclusive to SLE

• Nucleolar pattern

• Centromere pattern

If you test positive, your ANA generally remains positive, so there is no need for repeated ANA tests.

Anti-double-stranded DNA (dsDNA) is a subtype of ANA. It binds to double-stranded DNA in your cells. At high titers, this antibody is almost exclusively specific to people who have SLE.

Anti-dsDNA levels correlate with SLE activity: levels may increase dramatically during a lupus flare and decrease during treatment.

• Test is repeated.

High levels of anti-dsDNA are often associated with lupus nephritis.

*Family members of people who have lupus may also test positive for anti-dsDNA, even if they do not have lupus.

*Not all patients with SLE have the anti-dsDNA antibody. Patients who have SLE but do not have anti-dsDNA often have a related antibody, anti-Sm (see below).

Anti-Smith is a subtype of ANA. It acts against a collection of nuclear proteins that attach to DNA (the Smith proteins). It is highly specific for SLE.

Anti-Sm levels do NOT correlate with SLE activity (unlike anti-dsDNA): the anti-Sm antibody does not change in titer during a lupus flare or in response to treatment.

• Test is not repeated.

*Seen in most patients with SLE who do not have anti-dsDNA (some patients have both anti-dsDNA and anti-Sm).

Anti-RNP is a subtype of ANA. It acts against SnRNP70, an RNA-binding protein. It is not specific to lupus (can be positive in other rheumatoid diseases).

High levels of anti-RNP in the absence of other autoantibodies may indicate a different, lupus-like disease, called mixed connective tissue disease (MCTD).

SSA and SSB are subtypes of ANA. These two antibodies identify other molecules in the cell nucleus.

• If a patient has SLE, they will likely be positive for SSA and negative for SSB.

Patients with these antibodies:

• May develop Sjogren’s syndrome (hence, the “SS” in “SSA” and “SSB”), an autoimmune disorder characterized by dry eyes, dry mouth, and arthritis.

• Are more likely to suffer from sun-sensitive rashes.

• May have infants who develop neonatal lupus.

These antibodies attack and damage phospholipids. Phospholipids are lipids (fats) containing phosphorus and are important components of cell membranes.

High levels of aPL antibodies increase the risk of blood clotting in veins and arteries.

These antibodies can cause antiphospholipid syndrome (APS), characterized by the presence of aPL antibodies, recurring blood clots, pregnancy complications, and other clinical features.
*A positive aPL test alone, even in high levels, does not necessarily mean that a person has APS. To confirm a diagnosis of APS, the antibodies must be present in tests conducted 12 or more weeks apart.

Below are 3 common aPL antibodies:

• LA (lupus anticoagulant) *The name is confusing: LA is not specific to SLE and it isn’t a coagulant it actually increases your risk of blood clots.

• aCL (anticardiolipin antibody)

• aβ2GPI (beta-2 glycoprotein 1)

The complement system works with your immune system. It is made up of more than 30 proteins that destroy bacteria and viruses that invade your body. The proteins work in a cascade, which is activated when an antibody meets an antigen.

Remember that SLE causes production of autoantibodies. These autoantibodies activate complement proteins despite absence of an antigen. Thus, by measuring complement protein levels, we can monitor SLE activity.

The 2 most-commonly measured complement proteins are C3 and C4.

Results are usually in milligrams per deciliter (mg/dL) or grams per liter (g/L). Low levels of complement proteins (hypocomplementemia) indicate disease.

CBC measures the number of red blood cells, white blood cells, and platelets in your blood.

Red blood cells (RBCs):

Lupus can lead to low RBC (anemia) due to potentially damaged kidneys that do not produce erythropoietin, a hormone which normally stimulates the production of red blood cells.

• Measured by hematocrit (the percentage by volume of red cells in your blood) and hemoglobin (a protein in red blood cells that carries oxygen).

White blood cells (WBCs):

WBCs protect against infection and are a critical part of your immune system. That is why almost all untreated patients with lupus have low WBC (leukopenia).

Platelets (thrombocytes):

In lupus patients, the immune system attacks platelets, resulting in low platelets (thrombocytopenia).

Measures 14 different substances in a sample of your blood, providing information about your metabolism.

Liver function:

• Bilirubin - A substance produced by breakdown of red blood cells that is excreted from the body through the liver.

• Albumin - A protein made by the liver.

• Liver enzymes - Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP).

Kidney function:

• BUN (blood urea nitrogen) - A waste product that your kidneys normally help remove from your blood.

• Creatinine - A waste product of muscle activity that your kidneys filter and remove from your blood.

Electrolytes:

• Sodium - A mineral found in many foods. If the kidneys are damaged, sodium can build up in the body.

• Potassium - A mineral found in many foods that regulates heart and muscle function.

• Bicarbonate - Indicates the amount of carbon dioxide (CO2) in your blood.

• Chloride - Helps control fluid in the body.

Other:

• Glucose - An important energy source for the body. Checks for diabetes, the leading cause of kidney failure.

• Calcium - A mineral stored mainly in your bones that regulates many processes.

• Inflammation indicator.

• CRP levels correlate with disease activity and response to treatment.

• No diagnostic value (not indicative of any one specific disease).

• Infection, necrosis, trauma, malignancy, and allergic reaction can raise CRP.

*aka “sedimentation rate” or “sed rate”

This test measures the rate (in millimeters per hour) at which red blood cells (erythrocytes) settle to the bottom of a test tube of blood. Typically, red blood cells sink slowly. But inflammation makes red blood cells stick together in clumps. The clumps are heavier than single cells, so they sink faster.

• Inflammation indicator.

• No diagnostic value (not indicative of any one specific disease and subject to inaccuracy).

• Infection, anemia, and pregnancy can raise ESR.

When your kidneys are not working as well as they should, protein and blood cells can leak through your kidney's filters and into your urine.

A urinalysis examines a sample of your urine. It typically evaluates:

• pH − Acidic (low pH) is normal. Alkaline (high pH) may indicate a urinary tract infection (UTI) or kidney dysfunction.

• Protein − There should be no protein or trace amounts. When your kidneys are cleaning waste from your blood, filters prevent the protein from leaking out. If a large amount of protein is present in your urine, it may indicate kidney dysfunction.

• Protein/creatinine ratio − This test measures just how much protein is lost in the urine. Higher ratios are more suggestive of kidney dysfunction. Creatinine is a waste product excreted by the kidney at a constant rate, so it is used as a baseline to assess the rate of excretion of other substances.

• White blood cells (WBCs) − Only a low number of WBCs are normally present in urine. A high WBC count in urine often indicates that your body is fighting an infection or inflammation, usually in the urinary tract.

• Blood − More than a small number of red blood cells or presence of hemoglobin may indicate bladder or kidney disease or kidney stones (unless a woman is menstruating when the sample is collected).

• Casts (bits of cells) − May suggest more severe kidney issues.

• Bacteria – May indicate infection if the specimen was properly collected.

Chest X-ray

May reveal abnormal shadows indicating fluid or inflammation in your lungs.

Echocardiogram

Uses sound waves to produce real-time images of your beating heart. Checks for problems with your valves and other portions of your heart.

A biopsy is a procedure that removes tissue. The tissue is then examined for signs of inflammation or damage. People with lupus typically undergo skin and kidney biopsies.

• Kidney biopsy: lupus can harm your kidneys. Doctors may test a small sample of kidney tissue to determine what the best treatment for you is. These are done using a needle and an ultrasound to guide it.

• Skin biopsy: cutaneous lupus affects the skin. This biopsy can be performed to confirm diagnosis of skin lupus. These are done using a hollow needle.

Antinuclear Antibody Test (ANA Test) | Cleveland Clinic

Comprehensive Metabolic Panel (CMP): What It Is & Results | Cleveland Clinic ​

Lupus Blood Test Results: What to Know | HSS Rheumatology

Lupus - Diagnosis & treatment | Mayo Clinic