Systemic lupus erythematosus laboratory tests

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]

Diagnosis of lupus can be problematic. Making a correct diagnosis of lupus requires knowledge and awareness on the part of the doctor and good communication on the part of the patient.

An accurate medical history, physical examination and the results of laboratory tests help the doctor consider other diseases that may mimic lupus or determine if you truly have the disease.10

The most useful tests to aid a diagnosis identify certain autoantibodies often present in the blood of people with lupus. For example, the antinuclear antibody (ANA) test is commonly used to look for autoantibodies that react against components of the nucleus of the body's cells.

About 98% of people with lupus possess ANA, which can attack the nucleic material of your cells. However, there are a number of other causes of a positive ANA besides lupus, including infections and other autoimmune diseases.

Diagnostic tools for lupus include:

• Medical history
• Complete physical exam
• Laboratory tests including complete blood count (CBC), erythrocyte sedimentation rate (ESR), urinalysis, blood chemistries, complement levels, ANA and other autoantibody tests
• Skin biopsy
• Kidney biopsy.

Blood tests for lupus

Example of an ANA panel test.

In people with a positive ANA, more tests are usually performed to check for other antibodies that can help confirm a diagnosis.

Certain autoantibodies and substances in the blood can give information about which autoimmune disease, if any, is present. To check for other antibodies, doctors usually order an ANA panel, which checks for the following antibodies:17

• Anti-phospholipid
• Anti-double-stranded DNA
• Anti-Smith
• Anti-U1RNP
• Anti-Ro/SSA
• Anti-La/SSB.

1) Antiphospholipid antibodies (APLs)

APLs are a type of antibody directed against phospholipids. APLs are present in up to 60% of people with lupus.

A positive test is also used to help identify women with lupus that have certain risks that require preventive treatment and monitoring. Those risks include blood clots, miscarriage, or preterm birth.

2) Anti-double-stranded DNA antibody

The anti-double-stranded DNA antibody (anti-dsDNA) is a specific type of ANA antibody found in about 30% of people with lupus. The presence of anti-dsDNA antibodies often suggests a more serious form of lupus, such as lupus nephritis (kidney lupus).

3) Anti-Smith antibody

An antibody to Sm, a ribonucleoprotein found in the nucleus of a cell, is found 20% of people with lupus. Unlike anti-dsDNA, anti-Sm does not correlate with the presence of kidney lupus.

4) Anti-U1RNP antibody

Anti-U1RNP antibodies are commonly found along with anti-Sm antibodies in people with lupus. The incidence of anti-U1RNP antibodies in people with lupus is approximately 25%. Anti-U1RNP has been shown to be associated with features of scleroderma, including Raynaud's phenomenon. It has also been linked to other conditions, such as Jaccoud's arthropathy, a deformity of the hand caused by arthritis.

5) Anti-Ro/SSA and anti-La/SSB antibodies

Anti-Ro/SSA and anti-La/SSB are antibodies found mostly in people with lupus (30-40%) and primary Sjögren's syndrome. They are also commonly found in people with lupus who have tested negative for ANA.

Babies of mothers with anti-Ro and anti-La antibodies are at an increased risk of neonatal lupus, an uncommon condition that produces a temporary rash and can lead to congenital heart block. Therefore, women with lupus who wish to become pregnant should be tested for these antibodies.

6) Anti-histone antibodies

Antibodies to histones, proteins that help to lend structure to DNA, are usually found in people with drug-induced lupus, but they can also be found in people with SLE. However, they are not specific enough to lupus to be used to make a concrete diagnosis.

Serum (blood) complement test

A serum complement test measures the levels of proteins consumed during the inflammatory process. Low complement levels reflect that inflammation is taking place within the body. Variations in complement levels exist in different individuals simply due to genetic factors.

Some laboratories also include other antibodies in their panel, including antinucleoprotein or anticentromere.

Urine tests for lupus

Besides blood tests used to diagnose and monitor lupus, doctors use urine tests to diagnose and monitor the effects of lupus on the kidneys. These tests include the following:19

• Measurement of glomerular filtration rate and proteinuria: this test measures how effective the kidneys are at filtering the blood to eliminate waste products. It is conducted on urine collected over a 24-hour period
• Protein/creatinine ratio: this test is performed on a one-time urine sample. It measures for protein loss, an indicator of kidney function
• Urinalysis: urinalysis can be used in screening for kidney disease. The presence of protein, red blood cells, white blood cells and cellular casts may all indicate kidney disease.

Other laboratory tests are used to monitor the progress of the disease after diagnosis, and the effectiveness of medications include:18

• Erythrocyte sedimentation rate (ESR): a test that measures the amount of inflammation in your body
• C-reactive protein (CRP)/Westergren sedimentation rate: like the ESR, the CRP test measures inflammation. However, CRP usually changes more rapidly than ESR because it is made by the liver and secreted hours after the beginning of infection or inflammation
• Creatine phosphokinase (CPK): creatine is an enzyme (a protein that helps to elicit chemical changes in your body) found in your heart, brain, and skeletal muscles. When muscle tissue is damaged, CPK leaks into your blood. A high level of CPK usually indicates stress or injury to your heart or other muscles
• Coombs' test: the Coombs' test is used to detect antibodies that act against the surface of your red blood cells. The presence of these antibodies indicates a condition known as hemolytic anemia, in which your blood does not contain enough red blood cells because they are destroyed prematurely. An acquired form, autoimmune hemolytic anemia (AIHA), is present in about 10% of people with lupus and results from an immune system attack on your red blood cells.

X-rays and other imaging tests can help doctors see the organs affected by lupus.

A rheumatologist's diagnosis is considered the gold standard, with the American College of Rheumatology (ACR) using a standard classification scheme that requires 4 of 11 criteria for research definition. This system can sometimes fail to recognize or miss early and mild cases.

***

General lab exams	Complete blood count	leukopenia mild anemia thrombocytopenia
	serum creatinine	Elevated	suggestive of renal dysfunction
	Urinalysis with urine sediment	hematuria, pyuria, proteinuria, and/or cellular casts
Specefically lab exams for SLE diagnosis	ANA		positive in virtually all patients with SLE at some time in the course of their disease	If the ANA is positive, one should test for other specific antibodies such as dsDNA, anti-Sm, Ro/SSA, La/SSB, and U1 ribonucleoprotein (RNP)
	Antiphospholipid antibodies	lupus anticoagulant [LA], IgG and IgM anticardiolipin [aCL] antibodies; and IgG and IgM anti-beta2-glycoprotein [GP]
	complement levels	C3 and C4 or CH50
	Erythrocyte sedimentation rate (ESR)
	C-reactive protein (CRP)
	Urine protein-to-creatinine ratio
	Anti-dsDNA	highly specific for SLE in 70% of patients
	anti-Sm antibodies	highly specific for SLE lack sensitivity in 30% of patients
	Anti-Ro/SSA antibodies	in 30% of patients more commonly associated with Sjögren’s syndrome 15593352
	anti-La/SSB antibodies	in 20% of patients more commonly associated with Sjögren’s syndrome 15593352
	Anti-U1 RNP antibodies	in approximately 25 percent of patients with SLE Not specific, always present in patients with mixed connective tissue disease (MCTD) 15593352
	Antiribosomal P protein antibodies	high specificity for SLE & low sensitivity for SLE lack specificity for involvement of a particular organ system or disease manifestation.

If the initial ANA test is negative, but the clinical suspicion of SLE is high, then additional antibody testing may still be appropriate. This is partly related to the differences in the sensitivity and specificity among the methods used to detect ANA.

Laboratory exams to distinguish SLE from other diseases

anti-cyclic citrullinated peptide (CCP) antibodies	In patients with predominant arthralgias or arthritis may help exclude a diagnosis of rheumatoid arthritis (RA) higher specificity for RA and may be more useful for distinguishing the arthritis associated with RA. (See "Biologic markers in the diagnosis and assessment of rheumatoid arthritis", section on 'Rheumatoid factors' and "Biologic markers in the diagnosis and assessment of rheumatoid arthritis
Rheumatoid factor (RF)	less diagnostic utility since 20 to 30 percent of people with SLE have a positive RF
Serological studies for infection	serologic testing for human parvovirus B19	In patients with a brief history (for example, less than six weeks) of predominant arthralgias or arthritis
	serologic testing for hepatitis B virus (HBV) and hepatitis C virus (HCV)	in patients with multisystemic clinical findings
	serologic studies for Borrelia	n areas endemic for Lyme disease
	Testing for Epstein-Barr virus (EBV)
Creatine kinase (CK)	may reflect myositis, which is relatively uncommon in patients with SLE.	Myositis may also suggest an alternative diagnosis such as MCTD, polymyositis (PM), or dermatomyositis (DM).

Laboratory Findings

Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE.Several techniques are used to detect ANAs.Clinically the most widely used method is indirect immunofluorescence.The pattern of fluorescence suggests the type of antibody present in the patient's serum.

ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals. Subtypes of antinuclear antibodies include anti-Smith and anti-double stranded DNA (dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies (which are linked to drug-induced lupus). Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE. The anti-dsDNA antibody titers also tend to reflect disease activity, although not in all cases. Other ANA that may occur in SLE sufferers are anti-U1 RNP (which also appears in systemic sclerosis), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjögren's syndrome). SS-A and SS-B confer a specific risk for heart conduction block in neonatal lupus.

Other tests routinely performed in suspected SLE are complement system levels (low levels suggest consumption by the immune system), electrolytes and renal function (disturbed if the kidney is involved), liver enzymes, complete blood count and recently By proteomics, we can directly detect proteins as gene products as well as their alterations by post-translational modification and internal abscission which are characteristically observed in proteins.

Previously, the lupus erythematosus (LE) cell test was not commonly used for diagnosis because those LE cells are only found in 50–75% of SLE cases, and are also found in some people with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance.

As a summary:

• Medical history
• Complete physical examination
• Laboratory tests:

• Complete blood count (CBC)
• Erythrocyte sedimentation rate (ESR)
• Urinalysis
• Blood chemistries
• Complement levels
• Antinuclear antibody test (ANA)
• Other autoantibody tests (anti-DNA, anti-Sm, anti-RNP, anti-Ro [SSA], anti-La [SSB])
• Anticardiolipin antibody test

• Skin biopsy
• Kidney biopsy