Tuesday, 25 December 2012

Research: Plasma Exchange and JC Virus Immunity

Epub: Mancuso et al. JC virus detection and JC virus-specific immunity in natalizumab-treated Multiple Sclerosis patients.J Transl Med. 2012 Dec;10(1):248.

BACKGROUND: The use of natalizumab in multiple sclerosis (MS) may favour JC virus reactivation; this phenomenon is usually asymptomatic but can, albeit rarely, evolve into frank progressive multifocal leucoencephalopathy (PML).

METHODS: JCV-specific CD8+ T lymphocytes were evaluated by flow cytometry over a 24-month period in 24 natalizumab-treated MS patients in whom JCV DNA was or was not detected in blood using quantitative real-time polymerase chain reaction; all these cases were asymptomatic.


RESULTS: Perforin-and granzymes- (Molecules used to punch holes into infected cells to kill them) containing VP-1-specific CD8+ T lymphocytes were reduced whereas CD107a (a marker of degranulation of CD8 cells which have emptied their contents such as perforin and granzyme)-expressing cells were increased in JCV positive patients, suggesting an active degranulation of these cells; naive CD8+ T lymphocytes were also decreased whereas memory cells were increased in patients in whom JCV reactivation was observed.

CONCLUSION: The presence of a CD8+ T lymphocyte-mediated effector immune response offers a greater insight into reactivation of JCV and its clinical sequelae, and may help the monitoring of patients on natalizumab therapy.

This suggests that people infected with JC virus have ongoing immune control of the virus by CB8 T cells. In PML the battle favours the virus and the virus causes problems because the CD8 ces are kept out of the brain and can not do their job of killing virally infected cells. However, if there is too much virus in the brain and tysabri is removed so that cells can get in the brain then IRIS occurs and the cells kill the virally infected oligodendrocytes, which is not a cell type we want destroyed.



Epub: Subramanyam et al. The effect of plasma exchange on serum anti-JC virus antibodies. Mult Scler. 2012 Dec.

OBJECTIVE: Natalizumab, a highly effective treatment for multiple sclerosis (MS) and Crohn's disease, is associated with progressive multifocal leukoencephalopathy (PML). Upon suspicion or diagnosis of PML, plasma exchange (PLEX) is performed to remove natalizumab from the circulation, allowing immune reconstitution of the central nervous system. Since PLEX may also remove other circulating antibodies, we examined the effects of PLEX on serum immunoglobulin (IgG) and anti-JC virus (JCV) antibody levels in MS patients with and without PML.


METHODS: Serum samples from 12 natalizumab-treated patients without PML collected before, during and after PLEX were tested for IgG isotypes using a commercial assay, and for anti-JCV antibodies using a two-step enzyme-linked immunosorbent assay. Five natalizumab-treated PML patients who underwent PLEX were also tested for anti-JCV antibodies.

RESULTS: PLEX produced a two- to three-fold reduction in all IgG isotypes. Among patients without PML, 42% (five of 12 patients) had detectable anti-JCV antibodies before PLEX; in these patients, anti-JCV antibodies were reduced approximately two- to five-fold, with levels returning to 50-100 percent of baseline two weeks after the final PLEX. The five PML patients, all of whom had detectable anti-JCV antibodies before PLEX, experienced similar reductions in anti-JCV antibody levels following PLEX.

CONCLUSIONS: Our results indicate that PLEX effectively removes circulating antibodies; however, levels of endogenous anti-JCV antibody, unlike exogenously administered natalizumab, were replenished relatively quickly following PLEX. While interpretation of anti-JCV antibody levels during or within two weeks after PLEX may be problematic, humoral JCV immunity is not abolished by PLEX and antibody levels are rapidly restored.

If you get PML you want to get rid of the tysabri asap. Prof Gs idea was to do plasma exchange ,where you filter out the blood and remove the tysabri. The question was would this process remove JC virus antibodies, which will serve to neutralise the virus of help kill virally infected cells. This study shows that they get removed but because you are not removing the B cells then the body replenishes its protection. However there is a period of risk. However the CD8 cells will be there to try and destroy the virus.

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