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Usefulness of antinuclear antibody testing to screen for rheumatic diseases
P N Malleson1, M Sailer, M J Mackinnon
1Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Insights
The indirect immunofluorescence antinuclear antibody test (FANA) is not a reliable screening tool for childhood rheumatic diseases due to frequent false positives. Higher screening dilutions may improve diagnostic value for specific conditions like SLE and MCTD.
Area of Science:
- Pediatric Rheumatology
- Immunoserology
- Diagnostic Test Evaluation
Background:
- The indirect immunofluorescence antinuclear antibody test (FANA) is utilized in diagnosing autoimmune conditions.
- Screening for childhood rheumatic diseases requires accurate and efficient diagnostic methods.
- Human laryngeal epithelial carcinoma cells serve as a nuclear substrate in FANA testing.
Purpose of the Study:
- To evaluate the utility of the FANA test in screening for childhood rheumatic diseases.
- To assess the effectiveness of FANA using human laryngeal epithelial carcinoma cells as a nuclear substrate.
Main Methods:
- A retrospective review of FANA tests performed on pediatric patients.
- Data collected from British Columbia's Children's Hospital between March 1991 and July 1995.
- Analysis of FANA positivity rates in relation to rheumatic and non-rheumatic diagnoses.
Main Results:
- FANA tests were positive in 41% of all subjects and 65% of those with a confirmed diagnosis.
- FANA positivity rates were similar in children with and without rheumatic diseases (67% vs. 64%).
- At a 1:40 dilution, the test showed low sensitivity (0.63) and positive predictive value (0.33) for rheumatic diseases, but high sensitivity (0.98) and low positive predictive value (0.10) for SLE, MCTD, or overlap syndrome.
Conclusions:
- A negative FANA test is highly indicative of the absence of SLE or MCTD.
- A positive FANA test, even at high titers, has limited diagnostic value for general rheumatic diseases in children due to high false positive rates.
- Increasing screening dilutions to 1:160 or 1:320 could enhance diagnostic utility for SLE and MCTD while potentially reducing costs.
Objective:
To assess the usefulness of the indirect immunofluorescence antinuclear antibody test (FANA) using human laryngeal epithelial carcinoma cells as nuclear substrate, to screen for childhood rheumatic diseases.
Study Design:
A review of all FANA tests performed on children at British Columbia's Children's Hospital between 7 March 1991 and 31 July 1995.
Results:
FANA tests were positive at titres of 1:20 or greater in 41% of all subjects tested, and in 65% of all subjects in whom the diagnosis was obtained. FANA positivity occurred in 67% of those with a rheumatic disease, compared with 64% of those with a non-rheumatic disease (p = 0.4). More girls had high titre FANA positivity than boys independent of whether or not they had a rheumatic disease (p = 0.05). At a screening serum dilution of 1:40 a positive test has a sensitivity of only 0.63, and a positive predictive value of only 0.33 for any rheumatic disease. For systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), or overlap syndrome at a screening dilution of 1:40 the test has a very high sensitivity of 0.98, but a very low positive predictive value of only 0.10, the test having slightly better characteristics for boys than girls.
Conclusion:
Although a negative FANA test makes a diagnosis of SLE or MCTD extremely unlikely, a positive test even at moderately high titres of 1:160 or higher is found so frequently in children without a rheumatic disease that a positive result has little or no diagnostic value. It is suggested that a screening serum dilution of 1:160 or 1:320 would increase the usefulness of the test, by decreasing false positive tests, without significantly increasing false negative tests for SLE or MCTD, and would have the potential for considerable cost savings.