Source:Craig WY, Ledue TB, Johnson AM, Ritchie RF. The distribution of antinuclear antibody titers in “normal” children and adults.
J Rheum.
1999
;
26
(4):
914
–919.

Many children are referred to pediatric rheumatologists because laboratory testing revealed a “positive ANA.” These referrals are based on data obtained in the 1970–80s which concluded that children who have positive antinuclear antibodies (ANAs) usually develop identifiable autoimmune diseases.1 These conclusions were valid for ANA titers performed by the traditional “tissue ANA” method which used rat kidney as substrate. For the past decade, however, the substrate used to test for ANA has been Hep II cells, a human cell line. The use of Hep II cells has made it possible to detect a wide spectrum of antibodies (anti-centromere, anti-nucleolar, etc) but the test has a higher false positive rate than the tissue ANA. Tan et al surveyed the rate of positive ANA tests in healthy individuals at the dilutions usually used to differentiate between a “positive” and “negative” ANA.2 At a titer of 1:40, 31.7% of normal adults were positive, and at a titer of 1:80, 13% were still positive. The authors suggested that individual laboratories must determine what is “normal” in their labs.

Craig et al tested the blood of healthy children to determine how many had detectable levels of ANA using the standard immunofluorescence assay with Hep II cells as substrate. Three groups were tested: 200 healthy school children undergoing routine cholesterol screening as part of an unrelated study, 237 children whose sera had been sent to the lab to be tested for ANA, and 183 healthy blood donors age 20–63 years. Before including any child’s data in this study, diagnostic information from the group whose sera was tested for ANA was evaluated, and sera from children who had the following conditions were excluded from the study: a known autoimmune disease; symptoms suggestive of autoimmune disease (rash, photosensitivity, fever, fatigue, joint pain, arthritis, hematuria, stiffness or urticaria) and diagnosis reported to be associated with abnormal ANA titers (infection, hepatitis, allergy, or malignancy). Results demonstrated that 5% of healthy children 0–19 years of age had ANA titers greater than or equal to 1:64 (vs 18% of adults) and 2.5% had titers greater than or equal to 1:128 (vs 6% of adults). ANA titers tended to increase in the normal adult population, but this trend did not appear in the children tested. In children <20 years of age, the 50th centile was 1:8 and the 90th 1:32. There was no difference in titers between males and females in the pediatric group.

This is an important study, because it shows that only 5% of children will have ANA titers >1:64. Although healthy children with ANAs above this titer should, of course, be followed with routine pediatric exams, two large studies3,4 have shown that a positive ANA titer of 1:64 in a child with only non-specific musculoskeletal complaints means nothing. Patients who had a positive ANA and no signs...

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