Lupus is an autoimmune disease that can affect multiple organ systems in the body. One of the most common diagnostic tests for lupus is the antinuclear antibody (ANA) blood test. This looks for autoantibodies, which are antibodies the immune system makes against the body’s own tissues. A positive ANA test means autoantibodies were detected in the blood. However, the ANA test alone does not confirm a lupus diagnosis. Other specific antibody tests are used as well. This article will discuss what a positive ANA test result means, the role ANA titers play, and other diagnostic criteria used to diagnose lupus.
What Does a Positive ANA Test Mean?
The antinuclear antibody (ANA) test is often one of the first tests ordered when a doctor suspects an autoimmune disorder like lupus. It is used as a screening test to look for autoantibodies in the blood. A positive ANA test simply means autoantibodies were detected. However, a number of other conditions besides lupus can cause a positive ANA test.
Around 5-20% of healthy individuals with no disease will test positive for ANA. And it’s estimated that up to 15-30% of people overall will test positive at some point in their lives. So while a positive ANA may raise suspicion for an autoimmune disorder like lupus, it cannot alone confirm the diagnosis.
Some other common conditions associated with a positive ANA test include:
– Rheumatoid arthritis
– Sjögren’s syndrome
– Scleroderma
– Mixed connective tissue disease
– Autoimmune thyroid diseases like Hashimoto’s thyroiditis
– Autoimmune liver diseases like autoimmune hepatitis
– Inflammatory myopathies like polymyositis and dermatomyositis
– Juvenile idiopathic arthritis
– Drug-induced lupus
The pattern and titer level of the ANA (discussed more below) along with other clinical information is used to determine the likelihood of lupus versus another autoimmune condition. Around 95% of diagnosed systemic lupus erythematosus (SLE) patients will test positive for ANA. However, a negative ANA does not rule out lupus entirely either. Around 5% of lupus patients can have a negative ANA.
Why Do Healthy Individuals Test Positive for ANA?
A number of factors can cause someone without autoimmune disease to test positive for ANA, including:
– Older age – ANA prevalence increases with age even among healthy adults. 12% of healthy individuals over age 60 may test positive compared to only around 5% under 60.
– Infections – Active infections from viruses like EBV or hepatitis may stimulate transient ANA production.
– Inflammation – Inflammation from any cause (even something as simple as the common cold) can raise ANA levels temporarily.
– Family history – There may be a genetic predisposition to developing autoantibodies.
– Gender – Women naturally tend to have higher ANA levels compared to men.
– Medications – Certain prescription drugs like hydralazine, procainamide, and isoniazid can induce a positive ANA.
– Cancer – Some cancers including lymphomas and lung cancer may present with positive ANA tests.
In healthy individuals who test positive, ANA levels usually remain low and return to normal when the trigger resolves. Repeat testing of ANA months later often reverts back to a negative result. Whereas with autoimmune disease, ANA levels persist over time.
Understanding ANA Titers
ANA test results report both a positive or negative result along with a titer level. The titer refers to the dilution of blood at which autoantibodies are still detected. It is reported as a ratio, for example 1:40. The higher the second number, the higher the concentration of autoantibodies in the blood.
Examples of different ANA titer ranges:
– 1:40 – Weakly positive
– 1:80 – Low positive
– 1:160 – Moderate positive
– 1:320 – High positive
– 1:640 or greater – Very high positive
In healthy individuals or other conditions, ANA titers usually remain ≤1:160. Lupus patients commonly have ANA levels ≥1:80, and the majority have moderate to high positive ratios. However, around 20% of lupus patients have weakly positive titers between 1:40-1:60.
While higher titers increase suspicion for lupus, low titers alone cannot rule it out given a subset of patients have lower levels. Titer trends over time and correlation with clinical presentation is most useful in assessing results. For example, if a patient with lupus has a rising titer level over months where it was previously low, it may indicate a disease flare.
ANA Titer Trends in Lupus
– Titers ≥1:80 present in 70% of lupus patients
– Titers ≥1:160 present in 50%
– Titers ≥1:640 present in 25-30%
ANA levels fluctuate over time and do not directly correlate with lupus disease activity. Patients in remission may still test positive. However, significantly increasing titers in someone previously low can be one sign of a pending flare.
ANA Patterns in Lupus
Besides the quantitative titer, ANA tests also identify patterns in the immunofluorescence staining of cells. Different autoantibodies will bind to certain components of the nucleus in unique patterns. The pattern may provide clues as to what type of autoantibodies are present and possibility of certain disease manifestations.
Common ANA patterns seen in lupus include:
– Homogeneous – The most common pattern in lupus, present in 50-70% of patients. Stains the nucleus uniformly. Associated with antibodies to dsDNA and histones. Correlates with lupus kidney disease like glomerulonephritis.
– Speckled – Second most common, present in 30-50% of lupus patients. Stains the nucleus in a speckled pattern. Associated with antibodies to extractable nuclear antigens (anti-Sm, anti-RNP, anti-Ro, anti-La). Correlates with rashes, Raynaud’s phenomenon, and arthritis.
– Nucleolar – Present in 10-25% of lupus patients. Stains the nucleolar regions within the nucleus. Associated with antibodies to RNA polymerase I/III. Correlates with systemic disease like vasculitis.
– Peripheral/rim – Less common in lupus. Stains the outer edge of the nucleus. Associated with antibodies to dsDNA. Correlates with rashes and arthritis.
– Centromere – Rare in lupus. Stains the centromere areas of chromosomes. More associated with scleroderma.
Having a positive ANA with a homogeneous, speckled, or nucleolar pattern increases probability of lupus but must be interpreted in combination with other lab and clinical findings.
Other Antibody Tests Used to Diagnose Lupus
While a positive ANA is a hallmark of lupus, testing for other autoantibodies is critical to confirm diagnosis, determine prognosis, and predict disease manifestations. Some key specific antibody tests include:
– Anti-dsDNA – Antibodies to double stranded DNA are highly specific for lupus (90-95% specific) and found in 60-80% of SLE patients. Levels correlate with disease activity and kidney involvement.
– Anti-Sm – Antibodies to Smith nuclear antigen. Found in 10-30% of lupus patients and highly specific for SLE diagnosis. Associated with kidney disease and neurological manifestations.
– Anti-RNP – Antibodies to ribonuclear proteins. Present in 40% of lupus patients and associated with Raynaud’s phenomenon and joint inflammation.
– Anti-Ro/SSA – Anti-Ro found in 30-40% of lupus patients. Linked to rashes and sensitivity to sun. Anti-Ro strongly associated with neonatal lupus syndromes.
– Anti-La/SSB – Anti-La found in 10-15% of SLE patients. Also linked to photosensitivity rashes and neonatal lupus.
– Anti-ribosomal P – Linked to lupus psychosis and depression in 10-20% of lupus patients.
– Anti-phospholipid antibodies – anti-cardiolipin and lupus anticoagulant antibodies. Risk factor for miscarriages and blood clots in 15-30% of lupus patients.
– Anti-C1q antibodies – Found in 30-50% of lupus patients. Associated with kidney involvement and correlated with disease activity.
While a positive ANA is sensitive for lupus, additional antibody testing provides specificity for diagnosis. In particular, anti-dsDNA and anti-Sm have high specificity for SLE. Doctors also use antibody testing to predict complications like renal disease, guide treatment regimens, and monitor disease activity over time.
Other Diagnostic Criteria for Lupus
Given the limits of relying on ANA testing alone, classification criteria have been developed to definitively diagnose systemic lupus erythematosus combining clinical and lab information. The American College of Rheumatology (ACR) has established 11 criteria that are commonly used, with at least 4 required to classify lupus:
Clinical Criteria
1. Skin rashes – malar “butterfly” rash, photosensitivity, oral ulcers
2. Joint inflammation – nonerosive arthritis
3. Serositis – inflammation of the lining around lungs (pleuritis) or heart (pericarditis)
4. Kidney disorder – excessive protein or cellular casts in urine
5. Neurologic disorder – seizures, psychosis
6. Blood disorder – hemolytic anemia, low platelets or white cells
Immunologic Criteria
1. Positive ANA
2. Anti-dsDNA, anti-Sm, or antiphospholipid antibodies
3. Positive finding of antinuclear antibodies in the absence of medications known to induce them
Other Criteria
1. Oral ulcers – in absence of other causes like infections
2. Non-scarring hair loss
3. Fingertip skin lesions – pulp fingertip infarcts
While the ANA and other autoantibodies play an important role, lupus is ultimately a clinical diagnosis based on presenting signs and symptoms. Doctors will thoroughly assess medical history, perform a physical exam, and integrate both lab testing and clinical findings to reach a diagnosis. Since lupus can vary widely in severity and affected organs, diagnosis requires a holistic approach.
Conclusion
In summary, a positive ANA blood test is one piece of the puzzle in diagnosing lupus, but is not confirmatory alone. Levels above 1:80 increase suspicion for SLE, but around 20% of patients have lower titers. Specific autoantibodies like anti-dsDNA and anti-Sm have greater diagnostic accuracy. However, there is no one “positive number” that definitively indicates lupus. Clinical criteria and medical judgment along with lab testing guide diagnosis. While a positive ANA is a hallmark of SLE, the key is interpreting results in the full context of the patient presentation.