High level of agreement in a fixed vs. live cell-based assay for antibodies to myelin oligodendrocyte glycoprotein in a real-world clinical laboratory setting

Abstract

IntroductionAs recognition of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease becomes more widespread, the importance of appropriately ordering and interpreting diagnostic testing for this antibody increases. Several assays are commercially available for MOG testing, and based on a few small studies with very few discrepant results, some have suggested that live cell-based assays (CBA) are superior to fixed CBA for clinical MOG antibody testing. We aimed to determine the real-world agreement between a fixed and live CBA for MOG using two of the most commonly available commercial testing platforms.MethodsWe compared paired clinical samples tested at two national clinical reference laboratories and determined the real-world agreement between the fixed CBA and live CBA.ResultsOf 322 paired samples tested on both platforms, 53 were positive and 246 were negative by both methodologies (agreement 92.9%, Cohen’s kappa 0.78, [0.69-0.86]). Spearman correlation coefficient was 0.80 (p < 0.0001). Of the discrepant results, only 1 of 14 results positive by the live CBA had a titer greater than 1:100, and only 1 of 9 results positive by the fixed CBA had a titer of greater than 1:80. Lower titers on the fixed CBA correlate to higher titers on the live CBA.ConclusionOverall, there is excellent agreement between fixed and live CBA for MOG antibody testing in a real-world clinical laboratory setting. Clinicians should be aware of which method they use to assess any given patient, as titers are comparable, but not identical between the assays.

Comparison of live and fixed cell-based assay performance: implications for the diagnosis of MOGAD in a low-middle income country

“…The majority of our patients with low MOG IgG titres on FCBA had high (clear positive) titres on corresponding LCBA results. This has been emphasised in a recent study that found a high level of agreement between assays, but while titres were comparable, they were not identical ( 13 ). Testing at higher serum dilutions, as recommended in the international criteria, did not contribute additionally to the diagnosis.…”

“…In these studies, both live and fixed CBAs done at multiple centres were compared, using a limited number of samples from patients with either a pre-defined MOG IgG status or a known MOGAD phenotype (10,12). A recent study that compared assay performances in 322 patient samples found an excellent agreement between LCBA and FCBA for the diagnosis of MOGAD (13). The newly developed international MOGAD panel proposed diagnostic criteria that not only emphasised the clinical phenotypes associated with MOGAD but also laid down criteria for interpretation of CBA (both LCBA and FCBA) for definitive diagnosis (14).…”

Myelin oligodendrocyte glycoprotein antibody titers by fixed cell-based assay: positive predictive value and impact of sample collection timing

“…Following this operational change, assurance that anti-MOG titers by fixed CBA represent an improvement in the quality of anti-MOG testing we offer is essential to confirm clinical utility of titers we are now reporting as part of routine laboratory practice, and justify their burden on laboratory cost and workflow ( 11 ). This is particularly important for our laboratory because the recommendation by the 2023 MOGAD criteria to perform anti-MOG titers is primarily based on studies of titers using live CBA, which are not identical to titers using fixed CBA ( 8 , 9 , 12 , 13 ). With respect to how to best evaluate the clinical utility of fixed CBA anti-MOG titers, determinations of sensitivity and specificity are limited by the lack of an independent diagnostic gold standard to effectively discriminate between true-negative and false-negative anti-MOG results ( 5 ).…”