Performance Characteristics of Commercial Immunoassays for the Detection of IgG and IgM Antibodies to β2 Glycoprotein I and an Initial Assessment of Newly Developed Reference Materials for Assay Calibration.
OBJECTIVE
To investigate the performance characteristics and impact of newly developed reference calibrators on the commutability between anti-β2 glycoprotein I (anti-β2 GPI) immunoassays in antiphospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE).


METHODS
Immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-β2 GPI immunoassays from four manufacturers were evaluated. Serum samples from 269 patients (APS only, n = 31; SLE and APS, n = 83; SLE only, n = 129; pregnancy-related clinical manifestations without APS, n = 26) and 162 women with histories of successful pregnancies were tested. Results were expressed in kit-specific arbitrary units and in the calibrator reference units (RUs) based on 99th percentile cutoff values. Diagnostic accuracies, correlation between kits, and specific clinical manifestations in APS were investigated.


RESULTS
The sensitivities of the assays ranged from 15.8% to 27.2% (IgG) and 12.3% to 15.8% (IgM) while specificities ranged from 79.4% to 86.5% (IgG) and 80.6% to 84.5% (IgM). There was moderate to almost perfect interassay reliability (Cohen κ, 0.69-0.98), and Spearman correlation coefficients were generally improved when results of the IgG determinations were expressed in RUs.


CONCLUSIONS
Although qualitative agreements between immunoassays for both antibody isotypes are acceptable, correlations with APS clinical manifestations were kit dependent. Only the use of IgG reference material improved quantitative correlations between assays.
From Rheumatology/Internal Medicine, University of Texas Medical Branch, Galveston.
Rohan
R
Willis
From Rheumatology/Internal Medicine, University of Texas Medical Branch, Galveston.
Silvia S
SS
Pierangeli
ARUP Institute of Clinical and Experimental Pathology, Salt Lake City, UT.
Troy D
TD
Jaskowski
ARUP Institute of Clinical and Experimental Pathology, Salt Lake City, UT.
Elisabeth
E
Malmberg
Rheumatology, Hospital for Special Surgery, New York, NY.
Marta
M
Guerra
Rheumatology, Hospital for Special Surgery, New York, NY.
Jane E
JE
Salmon
Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD.
Michelle
M
Petri
Maternal Fetal Medicine, University of Utah and Intermountain Healthcare, Salt Lake City;
D Ware
DW
Branch
ARUP Institute of Clinical and Experimental Pathology, Salt Lake City, UT Department of Pathology, University of Utah, Salt Lake City. anne.tebo@hsc.utah.edu.
Anne E
AE
Tebo
D000328:Adult; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D002138:Calibration; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000592:standards*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D011933:Reagent Kits, Diagnostic / Q000592:standards; D012015:Reference Standards; D012680:Sensitivity and Specificity; D053482:beta 2-Glycoprotein I / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011933:Reagent Kits, Diagnostic; D053482:beta 2-Glycoprotein I
Antibodies; Antiphospholipid syndrome; Harmonization; Immunoassays; Standardization; β2 glycoprotein I