Which laboratory test is MOST SPECIFIC for the diagnosis of rheumatoid arthritis?

Correct answer: B. Anti-cyclic citrullinated peptide (anti-CCP) antibody

• A. ANTINUCLEAR ANTIBODY is the screening test for SYSTEMIC LUPUS ERYTHEMATOSUS, where it is highly sensitive but poorly specific. It is positive in perhaps 30–40% of rheumatoid patients and in a substantial minority of healthy people, particularly older women, so it establishes nothing here. This is the option most often chosen for a rheumatoid case, and it is the wrong disease's test.
• B. CORRECT. ANTI-CCP is the most SPECIFIC serological marker for rheumatoid arthritis, with specificity around 95%. It also appears EARLY, often years before symptoms, and its presence predicts more erosive and aggressive disease. Its sensitivity is comparable to rheumatoid factor at roughly 60–70%, which is why the two are ordered together in practice — rheumatoid factor for sensitivity, anti-CCP for specificity.
• C. ESR and CRP are markers of INFLAMMATION. They are used to gauge disease ACTIVITY and to monitor response to treatment, and they are raised in countless conditions. They diagnose nothing.
• D. RHEUMATOID FACTOR is an IgM antibody directed against the Fc portion of IgG. It is the traditional test and remains useful for its sensitivity, but it is poorly SPECIFIC — positive in Sjögren syndrome, hepatitis C, infective endocarditis, sarcoidosis and in healthy older people.

Note: ANA is the LUPUS test; for rheumatoid arthritis the diagnostic serology is rheumatoid factor plus ANTI-CCP. Worth carrying the whole set: anti-SSA (Ro) and anti-SSB (La) for Sjögren syndrome; anti-Scl-70 and anticentromere for systemic sclerosis; anti-dsDNA and anti-Smith for lupus, both highly specific.