One of the risk factor to develop progressive multifocal leukoencephalopathy (PML) among natalizumab-treated patients is the presence and high levels of anti-JCV antibodies. Our purpose was to test the association of different clinical and demographic variables with the presence and levels of anti-JCV antibodies in a Spanish cohort of multiple sclerosis (MS) patients during natalizumab treatment MATERIALS AND METHODS: All MS patients from two hospitals with at least one measure of the anti-JCV antibodies levels (2011-2014) were recruited, among them two PML cases. Anti-JCV antibody levels were assessed using two-step ELISA RESULTS: 1061 patients (16.3% natalizumab-treated) participated in this study. The seropositivity rate of anti-JCV antibodies was 58.2%. It increased with age (pcorrected =0.00005) and was lower among HLA-DRB1*15:01 carriers (pcorrected =0.049). The two PML patients were HLA-DRB1*15:01carriers. We had at least 3 quarterly anti-JCV antibody measurements (index value) from 137 patients, whose levels did not increase during natalizumab treatment. However, 5.8% of these patients had an increase of the index value higher of one point in a maximum of 6 months, something that was more frequently observed (p=0.054) among patients treated with immunosuppressant prior to natalizumab onset CONCLUSIONS: Old age and HLA-DRB1*15:01 were the factors that influence positively and negatively respectively our anti-JCV antibody prevalence, although our both PML cases were HLA-DRB1*15:01carriers. Most of our patients showed a stable anti-JCV antibody index values during natalizumab treatment.
There are certain truths about JCV risk: 1) being JCV seropositive in the first place; 2) natalizumab therapy for longer than 2 years; and 3) previous heavy immunosuppressant use. In addition, in 2016 there were some additional criteria introduced, namely IgM oligoclonal bands which may be protective, whereas low L-selectin positive CD4+ T-cells in long-term natalizumab therapy may increase risk. Here, Dominguez-Mozo et al. look for a genetic association to JCV antibody development.
They note that increasing age is an additional risk factor, but not male gender as previously described. They also noted that the risk was lowered if you were a carrier of HLA-DRB1*1501. Now HLA-DRB1*1501 has been consistently associated with MS in almost all populations studied, which makes it easier to find the link (it's like being stuck on a deserted island with only bananas to eat, the chances of your scurvy being linked to banana intake is pretty high!). Their total case accrual (i.e. those who developed PML) was also only two!
Despite this, there are some interesting findings; their JCV seropositivity status is 58.2% (in keeping with background exposure of ~60%), and their serconversion rate from negative to positive was 20.2% (again in keeping with previous rates). Converse, to other studies they did not find a change in JCV index levels with natalizumab treatment, but they do advocate periodic re-testing based on their finding of 5.8% of those studied exceeded an index value >1.5 in 6 months.
So Cliff Richard reached No.8 in the charts with his album 'When in Spain'; undoubtedly not one of his most well known works! I wonder how far this genetic link hypothesis would go...