Contributions
Abstract: P710
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Elevated seroreactivity against the JC Polyomavirus (JCPyV) is the main risk factor for natalizumab-associated progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS). A negative correlation between antibody levels to JCPyV and BK Polyomavirus (BKPyV), another virus in the Polyoma family, is a common serological observation. There is also evidence that patients with HIV-associated PML have lower antibody levels to BKPyV capsids compared to matched controls up to 2 years prior to PML diagnosis, suggesting a protective role for BKPyV in this population.
Objective: To investigate the association of BKPyV capsid antibody levels with natalizumab-associated PML in MS patients compared to control MS patients.
Methods: We obtained serum samples at the time of PML diagnosis from 10 natalizumab-associated PML cases and 212 control MS patients, of whom 130 currently treated with natalizumab and 82 treated with other disease-modifying treatment and never exposed to natalizumab. The samples were tested in ELISA assays for antibodies to JCPyV and BKPyV serotype 1 and 4 capsids.
Results: JCPyV antibody levels were higher in PML cases than controls (mean optical density [OD]: 1.461 vs. 0.415, p< 0.001). Among controls, natalizumab-exposed patients (n=130) had lower JCPyV, but higher BKPyV antibody levels, than patients (n=82) unexposed to natalizumab (p< 0.01). BKPyV serotype 1 antibody levels were significantly lower in PML cases than controls (mean OD: 0.628 vs. 0.932, p=0.033). This latter finding was confirmed in unadjusted (OR: 0.55, 95% CIs 0.32-0.98) and sex-, age-and natalizumab exposure-adjusted (OR: 0.45, 95% CIs 0.24-0.85) analyses. There was no significant difference in BKPyV serotype 4 reactivity between cases and controls.
Conclusions: Our findings show that lower levels of antibody to BKPyV serotype 1 are associated with PML in natalizumab-treated MS patients. The lower antibody levels to JCPyV in natalizumab-treated patients compared to drug unexposed patients may reflect the STRATIFY-based decision not to take natalizumab. This decision could in part explain the difference in BKPyV seroreactivity given that antibody levels to the viruses are inversely correlated. We speculate that high BKPyV antibody levels may be a marker of protection against PML mediated by cross-reactive cellular immunity. Assessing antibody levels to BKPyV may be useful to mitigate the risk of natalizumab-associated PML.
Disclosure:
Francesca Rossi: nothing to declare
Luca Prosperini: nothing to declare
Carlo Pozzilli: nothing to declare
Paola Cinque: nothing to declare
Laura Passeri: nothing to declare
Ruggero Capra: nothing to declare
Nicola De Rossi: nothing to declare
Raphael Viscidi: nothing to declare
Abstract: P710
Type: Poster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Elevated seroreactivity against the JC Polyomavirus (JCPyV) is the main risk factor for natalizumab-associated progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS). A negative correlation between antibody levels to JCPyV and BK Polyomavirus (BKPyV), another virus in the Polyoma family, is a common serological observation. There is also evidence that patients with HIV-associated PML have lower antibody levels to BKPyV capsids compared to matched controls up to 2 years prior to PML diagnosis, suggesting a protective role for BKPyV in this population.
Objective: To investigate the association of BKPyV capsid antibody levels with natalizumab-associated PML in MS patients compared to control MS patients.
Methods: We obtained serum samples at the time of PML diagnosis from 10 natalizumab-associated PML cases and 212 control MS patients, of whom 130 currently treated with natalizumab and 82 treated with other disease-modifying treatment and never exposed to natalizumab. The samples were tested in ELISA assays for antibodies to JCPyV and BKPyV serotype 1 and 4 capsids.
Results: JCPyV antibody levels were higher in PML cases than controls (mean optical density [OD]: 1.461 vs. 0.415, p< 0.001). Among controls, natalizumab-exposed patients (n=130) had lower JCPyV, but higher BKPyV antibody levels, than patients (n=82) unexposed to natalizumab (p< 0.01). BKPyV serotype 1 antibody levels were significantly lower in PML cases than controls (mean OD: 0.628 vs. 0.932, p=0.033). This latter finding was confirmed in unadjusted (OR: 0.55, 95% CIs 0.32-0.98) and sex-, age-and natalizumab exposure-adjusted (OR: 0.45, 95% CIs 0.24-0.85) analyses. There was no significant difference in BKPyV serotype 4 reactivity between cases and controls.
Conclusions: Our findings show that lower levels of antibody to BKPyV serotype 1 are associated with PML in natalizumab-treated MS patients. The lower antibody levels to JCPyV in natalizumab-treated patients compared to drug unexposed patients may reflect the STRATIFY-based decision not to take natalizumab. This decision could in part explain the difference in BKPyV seroreactivity given that antibody levels to the viruses are inversely correlated. We speculate that high BKPyV antibody levels may be a marker of protection against PML mediated by cross-reactive cellular immunity. Assessing antibody levels to BKPyV may be useful to mitigate the risk of natalizumab-associated PML.
Disclosure:
Francesca Rossi: nothing to declare
Luca Prosperini: nothing to declare
Carlo Pozzilli: nothing to declare
Paola Cinque: nothing to declare
Laura Passeri: nothing to declare
Ruggero Capra: nothing to declare
Nicola De Rossi: nothing to declare
Raphael Viscidi: nothing to declare