Promoting optimal care for Sjogren's, a common, serious, systemic disease.
LAB TESTS THAT SUPPORT
A SJOGREN'S DIAGNOSIS
Key Concepts
Be sure to read the Introduction to Diagnosis to better understand this page.
No single test diagnoses Sjogren’s early and accurately. Sjogren’s is a clinical diagnosis that is supported by, but cannot be ruled out by, diagnostic tests.
Sjogren’s is a distinct disease. Manifestations may overlap with other autoimmune rheumatic diseases (AIRDs) such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
Rheumatologists need to look at many factors to determine the correct diagnosis and to determine if more than one AIRD is present.
See the Myths About Diagnosis page to learn more about common myths that get in the way of diagnosis.
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Note: This page discusses laboratory tests in the context of diagnosis. There are many additional tests that are used for ongoing monitoring and care. There is no single test that can be used to monitor Sjogren's:​ rheumatologists must consider many systems in the body to assess how a patient is doing.
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Initial Sjogren's Labs
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ANA, SSA, SSB, CCP, RF, ESR, CRP (titers do not reflect disease severity)
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CBC with differential and platelets, serum potassium, LFTs
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UA, Random urine protein/Cr
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HIV, HEP C
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If SSA negative, minor salivary gland biopsy (MSGB), usually via rheumatology consult.
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Note: I consulted with several Sjogren’s experts when I developed this list of initial labs for primary care practitioners (PCPs). These tests may vary depending on the medical institution/ rheumatologist the PCP is working with.
Individual Labs Used For Diagnosis
Many of the tests used to support a Sjogren's diagnosis are part of the Sjogren's classification criteria. The classification criteria should not be misused as diagnostic criteria, which do not exist.
The "lip biopsy" aka minor salivary gland biopsy (MSGB)
This is discussed on a separate page. The MSGB is an important part of the Sjogren's classification criteria, but is not always positive in people with Sjogren's.
SSA (anti-Ro antibodies) is the most helpful blood test used to support a diagnosis of Sjogren's. SSA is also seen in other AIRDs, especially SLE, and sometimes in healthy people (5, 6, 9). SSA is one type of ANA, seen in 50-70% of Sjogren's patients.
See Myth #2 on the MYTHS ABOUT DIAGNOSIS page and SSA and Sjogren's to learn why this blood test is often negative in people with Sjogren's.
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SSB (anti-La) is usually (with exceptions) present only when SSA is present. For that reason, SSB is no longer used in the Sjogren's classification criteria.
SSB is present in about 40% of Sjogren’s patients. Like SSA, SSB may be seen in other autoimmune rheumatic diseases, especially SLE, and sometimes in healthy people (4, 5, 6, 9). Rheumatologists often like to see the SSB test prior to referral because it may be associated with organ involvement and certain cardiac arrhythmias.
Isolated SSB (without SSA) may still support a Sjogren's diagnosis. See Myth # 3 on the MYTHS ABOUT DIAGNOSIS page.
SSB and SSA are types of ANA, although about 10% of Sjogren's patients with SSA have a negative ANA test.
ANA (Anti-Nuclear Antibodies) - Positive in 50-80 % of Sjogren’s. ANA is positive in many other autoimmune rheumatic diseases (5, 6, 9). Some healthy people carry ANA, although usually at lower titers such as 1:80 or 1:160 (6). Infections, liver disease, and other conditions may also be associated with a positive ANA test. Higher titers are more likely to be associated with autoimmunity but may be caused by other conditions such as infections, malignancies (cancer) or certain medications.
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CCP (anti-citrullinated peptide, a subset of ACPA, anti-citrullinated protein antibodies)
Positive antibodies to CCP in the presence of erosive arthritis is suggestive of RA. However, these autoantibodies may be occasionally seen in Sjogren’s (3-10%) (5, 11), SLE, and other AIRDs. A rheumatologist’s expertise is needed for interpreting this test when a patient presents CCP/ACPA along with clinical signs of Sjogren’s. Sjogren's can cause inflammatory arthritis (201).
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RF (Rheumatoid factor) - Positive in many AIRDs and in 60-70% of Sjogren’s patients. Also positive in many infections, and occasionally in healthy people (6).
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CRP and ESR - These classic markers of inflammation are often completely normal in Sjogren's, even though Sjogren's is a systemic inflammatory disease. Inflammation can be detected by other inflammatory markers in Sjogren's but these are not standard tests that are readily available in the clinic setting.
Learn more here:
Sjogren's and Inflammation Part I
Sjogren's and Inflammation, Part II
CBC with differential and platelets
Cytopenia refers to low counts of various blood cell types. 30-60% of Sjogren's patients have one or more types of cytopenia (151, Ch. 6).
Cytopenia is a systemic feature of Sjogren's. It is one of the 12 major categories of the twelve categories in the ESSDAI, a research tool used to measure systemic activity.
Most cytopenia is mild and asymptomatic. Cytopenia can sometimes be caused by medications.
TYPES OF CYTOPENIA
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Low white blood cells (lymphopenia and neutropenia)
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Low platelets (thrombocytopenia)
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Low red blood cells (anemia)
The type of anemia caused by Sjogren's is called anemia of chronic disease. It is not the same as iron deficiency anemia, although the two may occur together. Severe thrombocytopenia or autoimmune hemolytic anemia are uncommon, but require management by a hematologist when they occur (10).
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Serum Potassium - Hypokalemia may indicate distal renal tubular acidosis, a kidney complication of Sjogren’s (10).
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UA, random urine protein and creatinine - Mild proteinuria (protein in the urine)is common in Sjogren’s, but usually occurs without symptoms. Learn more about Sjogren's and kidney disease.
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Liver tests (often inaccurately called liver function tests, or LFTs) - May indicate liver and/or biliary tract disease. Learn more about Liver Disease and Sjogren's.
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HIV/ Hepatitis C - These infections often have symptoms that overlap with Sjogren’s, such as sicca and flu-like fatigue. It is important to rule these out early on.
What about the ENA panel?
"The ANA test evaluates the presence or absence of autoantibodies, while the ENA panel aims to determine to what proteins in the cell nucleus the autoantibodies recognize. If an ANA test is negative, then the person is extremely unlikely to test positive for a specific antinuclear antibody (which is what the ENA panel tests). In Sjogren's, SSA sometimes occurs without a positive ANA."
More about Autoantibody Tests
How do autoantibodies help diagnose Sjogren’s and other CTDs?
In many patients with autoimmune rheumatic diseases, autoantibodies help clinicians distinguish between diseases that have overlapping manifestations. The relationship between autoantibodies and various diseases can be complicated. Many autoantibodies, including SSA, are associated with a number of diseases. There is no one "Sjogren's test" or "lupus test".
For more information, see So What is Sjogren's, Really?
What exactly are “Sjogren’s antibodies”?
SSA (anti-Ro) and SSB (anti-La) are also known as Sjogren’s antibodies. This is inaccurate because SSA and SSB are also seen in other autoimmune rheumatic diseases, especially SLE.
Among Sjogren's researchers and experts, the term “seropositive” usually refers to patients who are positive for SSA. Some researchers and rheumatologists may include ANA, SSB, or RF along with SS-A in their definition of seropositivity. Many primary care providers equate seropositive with positive RF. inconsistent terminology This can be very confusing!
ANA and SSA do not tell you how sick you are. They should not be used to guide monitoring and treatment decisions. Every Sjogren's patient, regardless of symptoms or antibody status, should be monitored for a wide variety of systemic manifestations.
Learn more about What is Good Sjogren's Care?
"In a patient who has Sjögren’s syndrome with SSA (Ro) and/or SSB (La) antibodies, the levels of these antibodies do not correlate with disease activity. In fact, these levels remain fairly constant in a given patient." ~ Alan Baer, MD, October 2012 The Moisture Seekers
Should SSA and ANA tests be used to follow the disease?
No. With rare exceptions, there is no need to repeat these tests for diagnosis once a positive SSA or ANA is obtained. Sometimes SSA and ANA may be repeated by a rheumatologist if previous results had were borderline (e.g., low titers) or as part of a research study.
See this article to learn why repeated tests are not generally recommended.
Other tests that can support a Sjogren's diagnosis
There are many other tests that can help point to a Sjogren’s diagnosis. Laboratory markers, such as cytopenia and hypergammaglobulinemia (elevated IgG) are common in Sjogren’s. Rheumatologists should consider these as part of the big clinical picture that suggests a Sjogren’s diagnosis (3), beyond the classification criteria.
Salivary Gland Ultrasound (SGUS) may eventually be added to the classification criteria, or even replace the lip biopsy (MSGB). However, like the lip biopsy, SGUS focuses on salivary gland damage, and not every person with Sjogren's will test positive.
See Myth # 6 on the MYTHS ABOUT DIAGNOSIS page.
Early markers of Sjogren's
New biomarkers are being investigated, including PSP (parotid secretory protein), CA-6 (carbonic anhydrase VI), various tear proteins (9, 15) and others.
Because these tests appear to produce many false positives, they are not widely accepted by rheumatologists as evidence of Sjogren's. However, further research is needed.
Updated 04-19-2024