Which laboratory tests are most useful for confirming a diagnosis of Sjögren's Syndrome?

The most useful laboratory tests for confirming a diagnosis of Sjögren's syndrome include detection of specific autoantibodies such as anti-Ro/SSA and anti-La/SSB antibodies, which are considered hallmark serological markers. These antibodies help differentiate Sjögren's syndrome from other autoimmune conditions and are integral to classification criteria ¹. Additionally, antinuclear antibody (ANA) testing is commonly positive in Sjögren's syndrome, supporting the autoimmune nature of the disease. Rheumatoid factor (RF) is also frequently elevated and can aid diagnosis, especially when combined with other serological markers ¹. Complement levels (C3 and C4) may be reduced in active disease, reflecting immune complex activity, although these are less specific. In some cases, salivary gland biopsy remains a key diagnostic tool, but laboratory tests are essential initial steps.

Recent literature emphasizes advances in laboratory diagnostics, including improved sensitivity and specificity of anti-Ro/SSA and anti-La/SSB assays, and highlights challenges in seronegative cases where these antibodies are absent (Li et al., 2025). In such cases, additional markers and clinical correlation are necessary (Lenti et al., 2022). Overall, the UK guidelines prioritize anti-Ro/SSA and anti-La/SSB antibody testing as the cornerstone laboratory confirmation, supported by ANA and RF, with complement levels providing adjunctive information ¹ (Li et al., 2025; Lenti et al., 2022).