Motivation: Midway last year, the anti-nuclear antibody (ANA) test started appearing rather useless to me. The ANA was positive at some titer in just about everyone we tested, and even when it was positive, we discarded it under the mantra of "non-specific." What is the range of ANA in the "healthy" population?
Paper: Tan, E.M., Feltkamp, T.E.W., Smolen, J.S. et. al. "Range of antinuclear antibodies in "healthy" individuals." Arthritis & Rheumatism (1997); 40: 1601-1611.
Methods: Fifteen international laboratories experienced in performing the ANA assay were asked to give samples from healthy individuals of different age groups and from patients with systemic lupus erythematosus (SLE), scleroderma, Sjogren's syndrome, rheumatoid arthritis (RA), and soft tissue rheumatism. Healthy was defined as working individuals between 20-60 years of age without physical or mental disabilities. Soft tissue rheumatism consisted of patients with non-articular pain.
Results:
Measurement Variability: Among the fifteen laboratories, inter-laboratory coefficient of variation for ANA was: 50.7% for 1:40 dilution, 44.3% for 1:80, 37.9% for 1:160, and 36% for 1:320. Intra-laboratory variation was about three times lower than the inter-laboratory coefficient of variation.
Normal Individuals: Overall, 46.7% tested negative on ANA. 31.7% tested positive at 1:40 dilution, 13.3% at 1:80 , 5% at 1:160, and 3.3% at 1:320 dilution.
1:160 dilution: At the the 1:160 dilution, the ANA was 95% sensitive for SLE, 86.5% sensitive for scleroderma, 74% sensitive for Sjogren's, 13.5% sensitive for RA, and 7.7% sensitive for soft tissue rheumatism. Compared to healthy controls, cutoff of 1:160 is 95% specific.
1:320 dilution: At the the 1:320 dilution, the ANA was 86.8% sensitive for SLE, 83.8% sensitive for scleroderma, 71.1% sensitive for Sjogren's, 2.7% sensitive for RA, and 3.8% sensitive for soft tissue rheumatism. Compared to healthy controls, cutoff of 1:320 is 96.7% specific.
Discussion: A cutoff of 1:160 appears to me a more reasonable value to use to separate possible pathology from variation in healthy individuals with only 5% of healthy population having titers of ANA higher than 1:160. To me, other surprising findings were how variable ANA is between laboratories and how poorly the ANA performs in detecting rheumatoid arthritis (only 13.5% sensitive for RA) even though it is a immunologic disorder with positive serologic markers. These figures must, of course, be interpreted with caution because the healthy population was derived from random samples submitted to laboratories. Aside from individuals having no physical disability, we do not know more specifics which could affect the performance of ANA. For instance, would a population of young women or older individuals with cancer have different characteristics in the ANA?
Paper: Tan, E.M., Feltkamp, T.E.W., Smolen, J.S. et. al. "Range of antinuclear antibodies in "healthy" individuals." Arthritis & Rheumatism (1997); 40: 1601-1611.
Methods: Fifteen international laboratories experienced in performing the ANA assay were asked to give samples from healthy individuals of different age groups and from patients with systemic lupus erythematosus (SLE), scleroderma, Sjogren's syndrome, rheumatoid arthritis (RA), and soft tissue rheumatism. Healthy was defined as working individuals between 20-60 years of age without physical or mental disabilities. Soft tissue rheumatism consisted of patients with non-articular pain.
Results:
Measurement Variability: Among the fifteen laboratories, inter-laboratory coefficient of variation for ANA was: 50.7% for 1:40 dilution, 44.3% for 1:80, 37.9% for 1:160, and 36% for 1:320. Intra-laboratory variation was about three times lower than the inter-laboratory coefficient of variation.
Normal Individuals: Overall, 46.7% tested negative on ANA. 31.7% tested positive at 1:40 dilution, 13.3% at 1:80 , 5% at 1:160, and 3.3% at 1:320 dilution.
1:160 dilution: At the the 1:160 dilution, the ANA was 95% sensitive for SLE, 86.5% sensitive for scleroderma, 74% sensitive for Sjogren's, 13.5% sensitive for RA, and 7.7% sensitive for soft tissue rheumatism. Compared to healthy controls, cutoff of 1:160 is 95% specific.
1:320 dilution: At the the 1:320 dilution, the ANA was 86.8% sensitive for SLE, 83.8% sensitive for scleroderma, 71.1% sensitive for Sjogren's, 2.7% sensitive for RA, and 3.8% sensitive for soft tissue rheumatism. Compared to healthy controls, cutoff of 1:320 is 96.7% specific.
Discussion: A cutoff of 1:160 appears to me a more reasonable value to use to separate possible pathology from variation in healthy individuals with only 5% of healthy population having titers of ANA higher than 1:160. To me, other surprising findings were how variable ANA is between laboratories and how poorly the ANA performs in detecting rheumatoid arthritis (only 13.5% sensitive for RA) even though it is a immunologic disorder with positive serologic markers. These figures must, of course, be interpreted with caution because the healthy population was derived from random samples submitted to laboratories. Aside from individuals having no physical disability, we do not know more specifics which could affect the performance of ANA. For instance, would a population of young women or older individuals with cancer have different characteristics in the ANA?
Thank you for the article, very informative post on nuclear antibodies.
ReplyDelete