Monday, May 12

Antibody Index Test May Aid PML Diagnosis on TYSABRI (Natalizumab)

A new test that compares JC virus (JCV) antibody levels in cerebrospinal fluid (CSF) with those in serum might be a useful complementary tool in the diagnostic workup for progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS) treated with natalizumab (Tysabri, Biogen Idec), a new study suggests.

Dr. Warnke explained that PML caused by JCV can be difficult to diagnose because early symptoms can be mistaken for a relapse in MS.

"At present, JCV-DNA detection by polymerase chain reaction (PCR) in cerebrospinal fluid is used for diagnosis of PML. However, false-negatives often occur, leading to delayed diagnosis and poor patient outcome in some cases," he said. "So we need more tests to allow earlier diagnosis."
"Our main findings are when you have clinical suspicion of PML — changes in behavior, personality, and motor function untypical for MS in patients treated with natalizumab, we might suspect it to be PML," he told Medscape Medical News.
He and his colleagues have proposed using the anti-JCV antibody specificity index (ASI-JCV) as an additional test for JCV DNA detection. This involves measuring the JCV antibody level in both serum and CSF and calculating the proportion of antibodies in CSF compared with serum.
In this study, Dr. Warnke and colleagues calculated the anti-JCV antibody specificity index in 25 patients who had developed PML while receiving natalizumab and in 47 patients also taking natalizumab who had not developed PML. Results showed that none of the control patients had JCV antibodies in CSF, whereas CSF antibodies were detected in more than 60% of the patients with PML.
Dr. Warnke stressed that this test would not replace the PCR test for JCV DNA. "But levels of JCV DNA detection and the antibody index tests do not exactly correlate, so here is an argument for using the antibody index alongside the DNA test for additional diagnostic value," he suggested.
"If we assume an estimate of 70% to 80% for the early diagnosis of PML using PCR, maybe we can increase this up to 85% using this antibody index test as well," he added.
The antibody index test is not yet commercially available.
"We have developed our own test and now use it at our hospital," he noted. "But it is not an established procedure yet. It is still a clinical research tool which needs further validation."
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