Sjögren’s syndrome (SS) is a systemic autoimmune disorder that primarily targets the body’s moisture-producing exocrine glands, such as the salivary and lacrimal glands, leading to chronic dry eyes and dry mouth. Because it is a systemic condition, Sjögren’s can also affect various organs and tissues throughout the body, making diagnosis and monitoring complex. Laboratory testing is fundamental for identifying this autoimmune activity and assessing its reach. While no single blood test confirms the diagnosis, a pattern of specific abnormal lab results provides the biological evidence needed to support a clinical evaluation and track disease progression.
Specific Autoantibodies for Diagnosis
The most definitive laboratory findings in Sjögren’s syndrome involve specific autoantibodies, which are proteins produced by the immune system that mistakenly target the body’s healthy components. Screening often begins with a test for Antinuclear Antibodies (ANA), found in up to 80% of patients with primary Sjögren’s syndrome. While a positive ANA result suggests an autoimmune condition, it is not specific to Sjögren’s, as it can be positive in many other disorders or in healthy individuals.
The hallmark antibodies for Sjögren’s syndrome are anti-Ro/SSA and anti-La/SSB. Anti-Ro/SSA antibodies are present in 50–75% of patients with primary SS and are considered a major classification criterion. These antibodies are associated with greater disease severity and a higher risk of systemic involvement, meaning the disease affects organs beyond the glands. Anti-La/SSB antibodies are less frequent (25–40% of SS patients), but their presence alongside anti-Ro/SSA is highly specific to the diagnosis. An isolated positive anti-La/SSB result without anti-Ro/SSA is uncommon in Sjögren’s syndrome.
Many Sjögren’s patients also test positive for Rheumatoid Factor (RF), an autoantibody typically associated with rheumatoid arthritis. RF is an IgM antibody that targets the Fc portion of IgG antibodies. Its co-occurrence is frequent (36–74% of cases) and is linked to a higher chance of systemic complications. Another serological abnormality is the presence of cryoglobulins, proteins that clot when exposed to cold temperatures. Cryoglobulins, particularly Type II, are associated with vasculitis, which is an inflammation of the blood vessels and a severe complication of Sjögren’s syndrome.
General Markers of Inflammation and Immune Activity
Several non-specific lab tests indicate chronic inflammation and B-cell overactivity characteristic of Sjögren’s syndrome. The Erythrocyte Sedimentation Rate (ESR) measures how quickly red blood cells settle in a test tube; a faster rate suggests inflammation due to increased proteins in the blood. An elevated ESR is common in 20–40% of patients and is often caused by the excessive production of antibodies.
C-Reactive Protein (CRP) is another marker of systemic inflammation produced by the liver. While CRP is often elevated in Sjögren’s patients, levels are typically much lower than those seen during an acute infection. Both ESR and CRP may remain within the normal range even when the disease is active, meaning they do not always reliably reflect the severity of the condition.
Hypergammaglobulinemia is another frequent finding, defined as an abnormally high level of immunoglobulins (antibodies) in the blood. This elevation reflects the overactivity of B-cells, the immune cells responsible for antibody production. This polyclonal increase in immunoglobulin levels, particularly IgG, indicates the chronic immune stimulation central to Sjögren’s syndrome.
Complement proteins, specifically C3 and C4, are part of the immune system’s defense mechanism. In some cases of Sjögren’s syndrome, especially those involving vasculitis or cryoglobulinemia, these complement levels may be low. Low C3 and C4 levels suggest these proteins are being consumed rapidly during immune complex formation and subsequent tissue damage.
Evaluating Systemic Organ Involvement
Specific lab tests monitor for potential damage to major organ systems, as Sjögren’s syndrome can extend beyond the exocrine glands. A Complete Blood Count (CBC) may reveal abnormalities like leukopenia (a low white blood cell count), seen in 15–20% of patients. Mild anemia, often classified as anemia of chronic disease, is also a common finding in long-term inflammatory conditions.
Renal function tests, such as Blood Urea Nitrogen (BUN) and creatinine, are important for screening for kidney involvement. A significant complication is tubulointerstitial nephritis, which can lead to renal tubular acidosis. This kidney problem may be indicated by a low serum bicarbonate or carbon dioxide level in the blood chemistry panel.
Liver Function Tests (LFTs), including enzymes like AST and ALT, are also monitored. Elevated liver enzymes can signal associated autoimmune liver conditions, such as primary biliary cholangitis, which occur more frequently in Sjögren’s patients. These tests indicate whether the systemic autoimmune process is actively damaging non-glandular tissues.
Interpretation and Next Steps
The diagnosis of Sjögren’s syndrome is rarely confirmed by a single abnormal lab result; instead, it relies on a specific pattern of serological findings combined with clinical symptoms and physical examination. The presence of anti-Ro/SSA and anti-La/SSB antibodies provides strong evidence of the underlying autoimmune process. However, about one-third of patients may not have these antibodies, a condition known as seronegative Sjögren’s, which necessitates further investigation.
In seronegative cases, or to confirm the diagnosis, blood work is interpreted alongside other diagnostic procedures. These procedures include the Schirmer’s test (to measure tear production) and a minor salivary gland biopsy, which is considered highly specific. The biopsy looks for characteristic lymphocytic infiltrates (clusters of immune cells) attacking the glandular tissue. Ultimately, the profile of abnormal blood tests, coupled with clinical data, must be interpreted by a specialist, typically a rheumatologist, to establish a definitive diagnosis and management strategy.