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Correction for age of anticardiolipin antibodies cut-off points
E Rapizzi1, A Ruffatti, M Tonello
1Division of Rheumatology, Department of Medical and Surgical Sciences, University of Padova, Padova, Italy.
Insights
Anticardiolipin antibody (aCL) levels vary significantly by age. New age-specific cut-off levels for IgG and IgA aCL are proposed to improve antiphospholipid syndrome diagnosis in children and the elderly.
Area of Science:
- Immunology
- Clinical Chemistry
Background:
- Anticardiolipin antibodies (aCL) of immunoglobulin (Ig) isotypes G, M, and A are established biomarkers for antiphospholipid syndrome (APS).
- Standard diagnostic cut-off levels for aCL were primarily established in adult populations.
Purpose of the Study:
- To evaluate the suitability of adult aCL cut-off levels for pediatric and elderly populations.
- To determine age-specific reference ranges for aCL in healthy children and elderly individuals.
- To propose new cut-off values to enhance diagnostic accuracy for APS across different age groups.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to measure IgG, IgM, and IgA aCL in sera from 100 healthy children (6 months–16 yrs) and 100 healthy elderly subjects (65–103 yrs).
- Results were compared against a reference group of 100 healthy adults (21–47 yrs).
- Cut-off points were calculated as mean + 2.5 standard deviations (SD) for each group.
Main Results:
- Significantly higher frequencies of IgG aCL were observed in children (26%) compared to adults (P = 0.0001), particularly in younger children (6 months–5 yrs).
- Elderly subjects showed a significantly higher frequency of IgA aCL (37%) compared to adults (P = 0.0001), especially in the oldest subgroup.
- New age-specific cut-off levels were proposed: IgG aCL 27.7 GPL for children, IgA aCL 13.8 APL for children, and IgA aCL 51.1 APL for the elderly.
Conclusions:
- Existing adult aCL cut-off levels may lead to false positives in children (IgG) and the elderly (IgA), and false negatives in children (IgA).
- Age-adjusted cut-off levels for aCL are necessary to improve the specificity and sensitivity of APS diagnosis in pediatric and geriatric populations.
- Implementing age-corrected reference ranges can optimize the clinical utility of aCL testing for antiphospholipid syndrome detection across the lifespan.
Abstract:
Immunoglobulin (Ig) isotypes G, M, and A of anticardiolipin antibodies (aCL) are considered markers of antiphospholipid syndrome (APS). They were determined by ELISA in sera of 100 healthy children aged between 6 months and 16 yrs (mean 5.4 yrs +/-3.4 SD) and 100 healthy elderly subjects aged between 65 and 103 yrs (mean 84.2 yrs +/-8.1 SD). The frequency with which they were detected was compared to that in sera of 100 healthy adults aged between 21 and 47 yrs (mean 25.8 yrs +/-5.2 SD) in order to evaluate if adult aCL cut-off levels were fit for pediatric and elderly populations. The cut-off points were calculated adding 2.5 SD to the mean values and, in the adult group, the results were 11.6 GPL, 7.5 MPL, and 23.9 APL for IgG, IgM, and IgA, respectively. In the children, IgG aCL were positive in 26 cases (26%), IgM and IgA aCL in 1 case (1%) respectively. Statistical comparison of these results to those of adults showed a higher significant frequency for children IgG aCL (P = 0.0001) with the major contribution by children aged between 6 months and 5 yrs, and a lower significant frequency for children IgA aCL (P = 0.041). In elderly subjects IgG aCL were positive in 12 cases (12%), IgM aCL in 4 (4%), and IgA aCL in 37 (37%). In a comparison of these values to those of adults, only elderly IgA aCL frequency was significantly higher (P = 0.0001) with the major contribution by the oldest subgroup. In order to avoid false positive results for IgG aCL in children and for IgA aCL in elderly, as well as false negative results for IgA aCL in children, we introduced three new cut-off points: (1) 27.7 GPL for IgG aCL in children; (2) 13.8 APL for IgA aCL in children; and (3) 51.1 APL for IgA aCL in elderly subjects. These data suggest that a correction for age of aCL cut-off levels should be considered to raise specificity and sensitivity for APS in pediatric as well as in elderly populations.