A Multilaboratory Peer Assessment Quality Assurance Program-Based Evaluation of Anticardiolipin Antibody, and beta₂-Glycoprotein I Antibody Testing

Abstract

We evaluated the performance of anticardiolipin (aCL) and beta2-glycoprotein I (beta2-GPI) antibody assays through a large external quality assurance program. Data from the 2002 cycle of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP) were analyzed for variation in reported numerical values and semiquantitative results or interpretations according to method type or group and in conjunction with available clinical data. High interlaboratory variation in numerical results and notable method-based variation, combined with a general lack of consensus in semiquantitative reporting, continues to be observed. Numerical results from cross-laboratory testing of 12 serum samples (for immunoglobulin G [IgG]-aCL, IgM-aCL, and IgG-beta2-GPI) yielded interlaboratory coefficients of variation (CVs) that were higher than 50% in six of 12 (50%) specimens for IgG-aCL, and 12 of 12 (100%) specimens for IgM-aCL and IgG-beta2-GPI. Semiquantitative reporting also varied considerably, with total (100%) consensus occurring in only four of 36 (11%) occasions. General consensus (where > 90% of participating laboratories agreed that a given serum sample gave a result of either negative or positive) was only obtained on 13 of 36 (36%) occasions. Variation in results between different method types or groups were also present, resulting in potential biasing of the RCPA QAP-defined target results by the large number of laboratories using the dominant aCL assays. Finally, laboratory findings frequently did not agree with the available clinical information. In conclusion, in a large proportion of specimens from the 2002 RCPA QAP cycle, laboratories could not agree on whether a serum sample tested was aCL-positive or aCL-negative, or beta2-GPI-positive or beta2-GPI-negative. Despite prior attempts to improve the standardization of testing and reporting practices, laboratory testing for aCL and anti-beta2-GPI still demonstrates significant interlaboratory and intermethod variation, which needs to be taken into account for the clinical interpretation of test results, especially those from different laboratories.

Prevalencia de anticuerpos antifosfolípidos en pacientes con conectivopatías

“…Estudios realizados en los países desarrollados relacionan la presentación de trombosis con el hallazgo de anticuerpos antifosfolípidos en pacientes con conectivopatías, sobre todo con anticoagulante lúpico y anticardiolipina IgG (12)(13)(14) .…”

The antiphospholipid syndrome: a large elephant with many parts or an elusive chameleon disguised by many colours?

“…In cross-laboratory studies, coefficients of variation approaching 50% in aCL and anti-β2GPI results have been consistently reported [29][30][31]. This means that the range of reported aCL and anti-β2GPI test results can differ substantially from the median result obtained from a group of diagnostic laboratories, including those using the same in-house or commercial test/assay.…”

“…It is also important to acknowledge the disappointing fact that many aPL tests are neither robust nor appropriately standardized, leading to much frustration amongst experts in the field as well as potential diagnostic errors in clinical and laboratory practice [18,19,[26][27][28][29]. In cross-laboratory studies, coefficients of variation approaching 50% in aCL and anti-β2GPI results have been consistently reported [29][30][31].…”

Anti-cardiolipin and anti-β2-glycoprotein I antibodies: normal reference ranges in northwestern Italy

“…These new assays have good analytical performances, excellent intra-assay variation (<10% CV) and may thus reduce the variability between laboratories -a major problem with ELISA kits. [3][4][5][6][7][8][9] However, even with these new platforms, the cut-off values for aCL and a-b2GPI must be carefully chosen, since the diagnostic performance strongly depends on the Correspondence to: B Montaruli, Laboratorio Analisi, AO Ordine Mauriziano, Largo Turati 62, 10128 Turin, Italy Email: bmontaruli@mauriziano.it upper limit reference ranges. It is recommended for each laboratory to establish in-house cut-off values obtained on a population of healthy volunteers with local reagent/instruments combination.…”

“…reporting and interpretation of the results). [3][4][5][6][7][8][9] Most commonly, aCL and a-b2GPI are measured by ELISA, although new technologies and automated platforms such as chemiluminiscent (CliA) and fluorescence enzyme (FEIA) immunoassays, have recently been marketed. These new assays have good analytical performances, excellent intra-assay variation (<10% CV) and may thus reduce the variability between laboratories -a major problem with ELISA kits.…”