Trampe AK et al. Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort. Neurology. 2012 May 16. [Epub ahead of print]
OBJECTIVE: To investigate the rate of seropositivity of anti-JC virus (JCV) antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab in the postmarketing setting and to assess anti-JCV serostatus in samples obtained before diagnosis of progressive multifocal leukoencephalopathy (PML).
METHODS: This was a blinded, retrospective cross-sectional and longitudinal analysis for anti-JCV antibodies using a confirmatory 2-step ELISA on 2,782 blood samples obtained from 2,253 patients nationwide for routine testing for anti-natalizumab antibodies during open-label treatment between 2007 and 2010.
RESULTS: Of the natalizumab-treated patients with MS, 58.8% tested positive for anti-JCV antibodies. The rate of seropositivity was higher in males and increased with age, with a plateau between age intervals 20-29 and 30-39 years. In longitudinal analyses, 19 of 194 (9.8%) patients converted from anti-JCV antibody-negative to seropositive status over 7.7 months; 4.7% reverted from antibody-positive to seronegative status over 7.9 months. Antibody levels, especially in the latter group, were low, indicating fluctuations around the lower cut point of the assay. Neither anti-JCV serostatus nor antibody levels were associated with immunosuppressive pretreatment, duration of natalizumab treatment, or anti-natalizumab antibodies. All samples obtained from 10 patients who developed PML were seropositive (13 samples before PML diagnosis [2.0-37.6 months]; 2 samples at diagnosis). Antibody levels in these samples were higher than those in samples from seropositive patients who did not develop PML.
CONCLUSIONS:These data argue for the potential clinical utility of JCV serology for PML risk stratification. However, further investigations of fluctuations in serostatus and of antibody levels for a more precise understanding of the predictive value are warranted.
Many questions-
ReplyDeleteRe 'These data argue for the potential clinical utility of JCV serology for PML risk stratification'
Why are they saying this now? I thought the clinical utility was already established. This blog has many posts on PML risk stratification
Re 'JC virus is one of the major causes of PML'
Isn't JC virus the only cause? Are there other causes too?
Re '4.7% reverted from antibody-positive to seronegative status'
How can antibodies disappear and what does it mean for PML risk?
Re 'Four subjects with JCV-DNA in urine and undetectable anti-JCV antibodies were retested for anti-JCV antibodies and three out of four resulted positive'
How can this happen? If the urine has JCV DNA, shouldn't there be anti-JCV antibodies too?
from the other post today
Re risk stratification..I agree with you mayeb they should read the blog.
ReplyDeleteAntibodies have a natural half-time and dissappear from circulation unless new ones are made.
In terms of PML risk it means some one perhaps tested negative may still harbor the virus.
1 in 10,000 people that is seronegative can get PML based on the risks posed.
The kidneys filter out alot of things and proteins are often broken down by the body before excretion. DNA can be detected by amplicification means and so low amounts of visus could be detected.
"If you have virus shouldn't you be antibody positive".
ReplyDeleteSometimes it takes time to sero convert. For example with HIV it can take weeks for you to become positive. So there can be a time lag before antibodies appear.
Looking for DNA means you amplify the viral copy number up. So it may exists at vey low levels and may perhaps be sub-immunogenic.
so it does not induce an antibody response.
Yes JC virus is the cause of PML, I thought there was another, guess I thought wrong
ReplyDelete