RANGE OF ANTINUCLEAR ANTIBODIES IN HEALTHY-INDIVIDUALS

Objective, To determine the range of antinuclear antibodies (ANA) in ' 'healthy'' individuals compared with that in patients with systemic lu pus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), Sjogre n's syndrome (SS), rheumatoid arthritis (RA), or soft tissue rheumatis m (STR), Methods. Fifteen international laboratories experienced in pe rforming tests for ANA by indirect immunofluorescence participated in analyzing coded sera from healthy individuals and from patients in the 5 different disease groups described above, Except for the stipulatio n that HEp-2 cells should be used as substrate, each laboratory used i ts own in-house methodology so that the data might be expected to refl ect the output of a cross-section of worldwide ANA reference laborator ies. The sera were analyzed at 4 dilutions: 1:40, 1:80, 1:160, and 1:3 20, Results, In healthy individuals, the frequency of ANA did not diff er significantly across the 4 age subgroups spanning 20-60 years of ag e. This putatively normal population was ANA positive in 31.7% of indi viduals at 1:40 serum dilution, 13.3% at 1:80, 5.0% at 1:160, and 3.3% at 1:320, In comparison with the findings among the disease groups, a low cutoff point at 1:40 serum dilution (high sensitivity, low specif icity) could have diagnostic value, since it mould classify virtually all patients with SLE, SSc, or SS as ANA positive, Conversely, a high positive cutoff at 1:160 serum dilution (high specificity, low sensiti vity) would be useful to confirm the presence of disease in only a por tion of cases, but would be likely to exclude 95% of normal individual s, Conclusion, It is recommended that laboratories performing immunofl uorescent ANA tests should report results at both the 1:40 and 1:160 d ilutions, and should supply information on the percentage of normal in dividuals who are positive at these dilutions, A low-titer ANA is not necessarily insignificant and might depend on at least 4 specific fact ors. ANA assays can be a useful discriminant in recognizing certain di sease conditions, but can create misunderstanding when the limitations are not fully appreciated.