Which autoantibody is most specific for the diagnosis of systemic lupus erythematosus?

• A. Anti-Smith (anti-Sm) antibodies
• B. Anti-dsDNA antibodies
• C. Anti-Ro (SSA) antibodies
• D. Antiphospholipid antibodies

Answer: (A)

Anti-Smith antibodies are the most specific marker for systemic lupus erythematosus. These antibodies target small nuclear ribonucleoprotein complexes that are essentially unique to SLE, so their presence strongly supports the diagnosis. They’re not very sensitive—many people with SLE don’t have anti-Sm—but when you do detect anti-Sm, it’s highly indicative of SLE.

Anti-dsDNA antibodies are also associated with SLE and relate to disease activity, especially lupus nephritis, but they can appear in a small subset of other conditions, so they’re less specific than anti-Sm. Anti-Ro/SSA antibodies are more commonly linked to Sjögren’s syndrome (and can occur in a subset of SLE patients), so they’re not as specific to SLE. Antiphospholipid antibodies can be found in several diseases and even in healthy individuals, so they’re not diagnostic on their own for SLE.

In short, a positive anti-Smith antibody test is the most specific serologic finding for confirming SLE.