Range of antinuclear antibodies in
September 8, 1997
OBJECTIVE: To determine the range of antinuclear antibodies
(ANA) in "healthy" individuals compared with that in patients
with systemic lupus erythematosus (SLE), systemic sclerosis
(SSc; scleroderma), Sjogren's syndrome (SS), rheumatoid
arthritis (RA), or soft tissue rheumatism (STR).
METHODS: Fifteen international laboratories experienced in
performing 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 stipulation that HEp-2 cells should be used as
substrate, each laboratory used its own in-house methodology
so that the data might be expected to reflect the output of a
cross-section of worldwide ANA reference laboratories. The
sera were analyzed at 4 dilutions: 1:40, 1:80, 1:160, and 1:320.
RESULTS: In healthy individuals, the frequency of ANA
did not differ significantly across the 4 age subgroups
spanning 20-60 years of age. This putatively normal population
was ANA positive in 31.7% of individuals 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
specificity) could have diagnostic value, since it would
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 sensitivity) would be useful
to confirm the presence of disease in only a portion of cases,
but would be likely to exclude 95% of normal individuals.
CONCLUSION: It is recommended that laboratories performing
immunofluorescent ANA tests should report results at both the
1:40 and 1:160 dilutions, and should supply information on the
percentage of normal individuals who are positive at these
dilutions. A low-titer ANA is not necessarily insignificant
and might depend on at least 4 specific factors. ANA assays
can be a useful discriminant in recognizing certain disease
conditions, but can create misunderstanding when the
limitations are not fully appreciated.
Tan EM, Feltkamp TE, Smolen JS, Butcher B, Dawkins R, Fritzler MJ, Gordon T, Hardin JA, Kalden JR, Lahita RG, Maini RN, McDougal JS, Rothfield NF, Smeenk RJ, Takasaki Y, Wiik A, Wilson MR, Koziol JA