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Anti-Synthetase Syndrome — SCE Rheumatology MCQ

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HardAutoimmune SerologyAnti-Synthetase SyndromeSCE Rheumatology

A 52-year-old woman has inflammatory polyarthritis, mechanic's hands and NSIP-pattern interstitial lung disease, but a normal creatine kinase and no objective muscle weakness. HEp-2 indirect immunofluorescence is reported as: "nuclear ANA negative; isolated cytoplasmic fine-speckled staining (AC-20) to 1:640". Anti-Jo-1 is positive on two different assay platforms. Which interpretation is most accurate?

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Correct answer: E — The nuclear ANA is negative, but the cytoplasmic pattern reflects clinically significant anti-synthetase reactivity.

Option E is correct. Anti-Jo-1 targets histidyl-tRNA synthetase, a cytoplasmic aminoacyl-tRNA synthetase, and may produce a cytoplasmic fine-speckled HEp-2 pattern rather than nuclear fluorescence. Some laboratories therefore report the nuclear ANA component as negative while separately describing clinically important cytoplasmic staining. Confirmed anti-Jo-1 together with NSIP-pattern interstitial lung disease, inflammatory arthritis and mechanic's hands strongly supports anti-synthetase syndrome; myositis may be absent initially, so normal creatine kinase does not exclude it. The pattern neither establishes SLE nor characterises drug-induced lupus. Orthogonal confirmation of anti-Jo-1 and a compatible phenotype also make contamination or an incidental false-positive result unlikely.

Reference: BMJ Open Respiratory Research, "Clinicoserological features of antisynthetase syndrome-associated interstitial lung disease presenting to respiratory services: comparison with idiopathic pulmonary fibrosis and ASyS diagnosed in rheumatology services", autoantibody testing and discussion, 2021. https://bmjopenrespres.bmj.com/content/8/1/e000829