Stratify JCV Antibody ELISA Test: Who Gets What? Issues of Sensitivity Versus Specificity
Since the inception of Stratify JCV Antibody ELISA test (Stratify) use as a safeguard to predict potential development of progressive multifocal leukoencephalopathy (PML), there has been considerable reservation about use of natalizumab (NTZ) in seropositive patients or seroconverters. Stratify indices have contributed to this confusion with JCV titers of greater than 1.5 felt to be of more significance. Apprehension regarding the use of NTZ seems justified given the fact that there is no known cure for PML. At the same time, Stratify has provided a false sense of security in predicting probability of PML in patients considered candidates for NTZ therapy.
To assess whether the Stratify should be used as the ‘gold standard’ to determine initiating or continuing natalizumab (NTZ) therapy. Comparison will be made between Stratify and JCV DNA PCR in whole blood, urine, and CSF.
45 MS patients were followed over a period of 2 to 9 years. Baseline EDSS scores ranged from 2.0-7.0 and were followed serially. Monthly peripheral blood work, including CD4/CD8 ratios were obtained on all patients. Yearly brain, cervical, and thoracic (when appropriate) MRI scans were obtained per TOUCH protocol. Stratify was performed every 6 months. Additionally, JCV DNA PCR in whole blood, CSF, and urine were obtained at yearly intervals and these results were extrapolated and compared to Stratify results. Comparison was made with clinical examination, MRI scanning, Stratify, JCV DNA PCR in whole blood, urine, CSF, EDSS scoring, and relapse rate while on NTZ.
30 of 45 (67%) patients on NTZ were seropositive for JCV antibodies via Stratify prior to treatment initiation. Of these, 56% had JCV indices > 1.5. Seroconversion to a positive antibody titer occurred in 10 (22%) patients over the 5 year course. There was no correlation between NTZ treatment duration and the development of Stratify positivity. One patient had been on NTZ for 9 years without seroconversion. All patients who were Stratify positive were negative when compared to DNA PCR in whole blood, CSF, and urine. 2 patients withdrew from the study (one at 3 years and one at 5 years) because of more frequent MS relapses despite negative NABs to NTZ. One patient developed positive conversion of whole blood DNA PCR (2%) who was also Stratify positive. Two patients had DNA PCR seroconversion in urine (4%). No patient developed seroconversion in CSF. No patient developed PML. CD4/CD8 ratios in blood remained stable without evidence for peripheral immunosuppression.
Although Stratify may be a sensitive test, it offers little in terms of specificity in predicting the possible occurrence of PML in NTZ treated patients, and did not render specificity for determining NTZ therapy. In fact, use of Stratify testing may hamper treatment of MS patients who would otherwise have had considerable clinical benefit, and should not be used as a sole measure in therapeutic decisions.