Antinuclear antibodies: when to order them, what to do if positive

Internal medicine and immunology · Abnormal laboratory result · updated 2026-10-30

BioMG follows French guidelines. Adapt it to the guidelines and the tests available where you practise.

Frequency: “Healthy” subjects: antinuclear antibodies positive in 13% at 1/80 and 5% at 1/160 ^[1]

Positive ANA (titre ≥ 1/160 or suggestive clinical sign): characterise and look for organ involvement

Anti-dsDNA antibodies (if the laboratory has not already done them)
Anti-ENA antibodies (at least anti-Sm, anti-SSA/Ro60, anti-SSB, anti-RNP)
FBC
Serum creatinine with eGFR
Complement fractions C3 and C4 (if lupus suspected)if neededHypocomplementaemia is an argument in favour of lupus; only the fall in C3 is relatively specific ^[2].
Urine protein:creatinine ratio (spot sample) (if the dipstick shows proteinuria)if neededProteinuria positive on dipstick is quantified by the urine protein:creatinine ratio; a ratio ≥ 0.5 g/g raises the question of a renal biopsy ^[2].
HIV, HCV and parvovirus B19 IgG and IgM serology (if recent presentation that may be viral)if neededThe PNDS (French national protocol for diagnosis and care) suggests them to exclude a viral infection that sometimes mimics lupus at onset ^[2].

Detailed explanation and international comparison (in French): read it in English (machine translation)

Signs suggestive of lupus? If the picture suggests lupus, follow the page Lupus for the initial tests.
Dry mouth or dry eyes? If the patient complains of dryness, see the page Sicca syndrome (suspected Sjögren's disease).

“Screening” antinuclear antibodies without suggestive clinical signs (isolated fatigue, diffuse pain, routine tests): the French laboratory fee schedule (NABM) provides for them only if the clinical picture suggests an autoimmune disease ^[4], and an isolated positive result does not define a disease ^[3].
Follow-up anti-ENA: their level does not track disease activity, they are tested only at diagnosis ^[3].
Anti-denatured DNA (single-stranded) antibodies and IgM-isotype anti-dsDNA antibodies: no diagnostic value for lupus ^[2].
Anti-nucleosome, anti-ribosomal P protein, anti-Ku, anti-C1q antibodies as a routine: not to be tested for from the outset ^[2].

No other laboratory test: re-examine the patient and review them if a clinical sign appears.

Detailed explanation and international comparison (in French): read it in English (machine translation)

Repeating antinuclear antibodies “just to see” without any new clinical element: an isolated low titre does not define a disease ^[3], and autoimmunity tests are provided for only if the clinical picture suggests an autoimmune disease ^[4].

Sources (15)