Abstract
The aim of the study was to assess RF cross-reactivity to animal antibodies used in immunoassays, and to test if selected commercial immunoassays are vulnerable to interference from RF, causing false test results. Our study included samples from patients with RF-positive rheumatoid arthritis (RA) and controls (patients with RF-negative RA and psoriatic arthritis), included in an early arthritis-cohort. Reactivity to mouse IgG1, mouse IgG2a, rabbit IgG, bovine IgG, sheep/goat IgG and human IgG was analysed using in-house interference assays. RF-positive sera with strong reactivity to mouse IgG1 were analysed in three commercial immunoassays. To reveal interference, results before and after addition of blocking aggregated murine IgG1 were compared. Samples from 124 RF-positive RA patients and 66 controls were tested. We found considerably stronger reactivity toward animal antibodies, particularly mouse IgG1 (73% vs. 12%) and rabbit IgG (81% vs. 6%), in sera from RF-positive RA-patients compared to controls (p < 0.001). After selecting samples for testing in commercial assays, interference was revealed in 6/30 sera in the Architect β-hCG assay, 7/10 sera in the 27-plex cytokine assays, and in 2/33 samples in the Elecsys Soluble Transferrin Receptor assay. Our study revealed considerable RF reactivity to animal antibodies used in immunoassays and RF was associated with falsely elevated results in immunoassays used in clinical care and research. Clinicians, laboratorians, researchers and assay manufacturers must be alert to the risk of falsely elevated test results in RF-positive RA patients.
Highlights
Immunoassays are widely used to measure analytes in clinical practice for diagnostics and disease monitoring, as well as in research
The main aims of this study were to assess the prevalence of Rheumatoid factor (RF) reactivity to animal antibodies and to test if selected commercial immunoassays are vulnerable to interference from RF-positive sera from an early arthritis population
We have assessed the prevalence of anti-animal and antihuman IgG-reactivity and the associated risk of interference in immunoassays commonly used in clinical care and research, in a large cohort of recent-onset rheumatoid arthritis (RA) patients
Summary
Immunoassays are widely used to measure analytes in clinical practice for diagnostics and disease monitoring, as well as in research. Rheumatoid factor (RF) is a group of autoantibodies with reactivity to the Fc of human IgG, and may behave as heterophilic antibodies by crossreacting with antibodies from other species [4, 5]. RF and heterophilic antibodies have the potential to cause falsely elevated test results by cross-linking the assay antibodies,. A much publicised case from the late 1990s illustrates the potential consequences when incorrect test results caused by interference lead to mismanagement of patients [7]. Repeated elevated results for human chorionic gonadotropin (hCG) in a young, non-pregnant woman, misled her gynaecologists to suspect trophoblastic disease. No malignant disease was found in biopsies or surgical resectates, her hCG remained unchanged and was shown to be falsely elevated when a sample was sent for analysis in a different hCG-assay. In addition to harming patients, false test results have the potential to confound research results
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