ECTRIMS eLearning

Type 0 blood group associates with higher anti-JCV antibody levels
ECTRIMS Learn. Warnke C. 10/25/17; 199764; EP1744
Clemens Warnke
Clemens Warnke
Contributions
Abstract

Abstract: EP1744

Type: ePoster

Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments

Background: JC virus (JCV) associated progressive multifocal leukoencephalopathy (PML) occurs during therapy for multiple sclerosis (MS). Detection of anti-JCV antibodies, and the so-called serum 'index values' are accepted risk factors for the later development of PML. The reasons why higher antibody levels to JCV associate with higher risk of developing PML are not well understood. Host genetic factors may influence the anti-JCV antibody levels, and thus may be the underlying cause for such link. Putative host gene candidates could include those that encode the ABO blood groups, with the blood group 0 previously noted to display a trend for over-representation in cases with PML (Khoury et al, JAMA Neurology 2013).
Aim: To assess if type O blood group associated with higher levels of anti-JCV antibodies, and if type O blood group therefore was a risk factor for the development of PML.
Methods: Determination of ABO blood group antigens on blood samples of 62 patients with PML, and 64 controls without PML. Sera were tested in an enzyme-linked immunosorbent assay using a JCV-VP1 protein fused to GST as antigen, and anti-JCV antibody levels in arbitrary units (AU) were determined as previously published (Warnke et al, MSJ 2013).
Results: Of the patients with PML and known underlying disease, 62% were patients with MS treated with natalizumab, 14% were HIV positive, and 11% had underlying malignancy. JCV antibody levels were higher in patients with blood group 0 compared with all other blood groups, irrespective of the development of PML (0: median AU: 136; not 0: median AU: 53; p< 0.01). This association was not observed for the closely related BK virus. Of the 62 patients with PML, 29 (47%, 95% CI 35-59%) were of blood group 0, which showed a non-significant trend to differ from the expected distribution in the German population (41%), and the MS controls studied (23/64=36%, 95% CI 25-48%). In the natalizumab-associated PML subgroup, this deviation was the most prominent with 16 of the 29 cases having blood group 0 (55%, 95% CI 38-71%).
Conclusion: The ABO blood group 0 antigen associates with higher anti-JCV antibody levels, and may impact the risk of the later development of PML. The non-significant over-representation of blood group 0 in cases with PML was in line with a previous publication. Larger studies are warranted to assess a potential value of host genetic risk factors, such as the ABO status, for PML risk prediction during immunotherapy.
Disclosure:
PF: nothing to disclose.
HPH: consulting fees and fees for serving on steering and data monitoring committees from Bayer Healthcare, Biogen, GeNeuro, Medimmune, Merck, Novartis, Receptos / Celgene, Roche, Sanofi Genzyme, Teva with approval by the Rector of Heinrich-Heine-University.
TO: has received lecture and/or advisory board honoraria from Biogen, Novartis, Genzyme, and Merck. The same companies have provided unrestricted MS research grants.
OA: accepted speakers honoraria and research funding from Biogen.
CW: consulting and/or research funding: Biogen, Novartis, Teva.
Study support: grant of the European Charcot Foundation and the Hertie-Foundation to CW (P1150063).

Abstract: EP1744

Type: ePoster

Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments

Background: JC virus (JCV) associated progressive multifocal leukoencephalopathy (PML) occurs during therapy for multiple sclerosis (MS). Detection of anti-JCV antibodies, and the so-called serum 'index values' are accepted risk factors for the later development of PML. The reasons why higher antibody levels to JCV associate with higher risk of developing PML are not well understood. Host genetic factors may influence the anti-JCV antibody levels, and thus may be the underlying cause for such link. Putative host gene candidates could include those that encode the ABO blood groups, with the blood group 0 previously noted to display a trend for over-representation in cases with PML (Khoury et al, JAMA Neurology 2013).
Aim: To assess if type O blood group associated with higher levels of anti-JCV antibodies, and if type O blood group therefore was a risk factor for the development of PML.
Methods: Determination of ABO blood group antigens on blood samples of 62 patients with PML, and 64 controls without PML. Sera were tested in an enzyme-linked immunosorbent assay using a JCV-VP1 protein fused to GST as antigen, and anti-JCV antibody levels in arbitrary units (AU) were determined as previously published (Warnke et al, MSJ 2013).
Results: Of the patients with PML and known underlying disease, 62% were patients with MS treated with natalizumab, 14% were HIV positive, and 11% had underlying malignancy. JCV antibody levels were higher in patients with blood group 0 compared with all other blood groups, irrespective of the development of PML (0: median AU: 136; not 0: median AU: 53; p< 0.01). This association was not observed for the closely related BK virus. Of the 62 patients with PML, 29 (47%, 95% CI 35-59%) were of blood group 0, which showed a non-significant trend to differ from the expected distribution in the German population (41%), and the MS controls studied (23/64=36%, 95% CI 25-48%). In the natalizumab-associated PML subgroup, this deviation was the most prominent with 16 of the 29 cases having blood group 0 (55%, 95% CI 38-71%).
Conclusion: The ABO blood group 0 antigen associates with higher anti-JCV antibody levels, and may impact the risk of the later development of PML. The non-significant over-representation of blood group 0 in cases with PML was in line with a previous publication. Larger studies are warranted to assess a potential value of host genetic risk factors, such as the ABO status, for PML risk prediction during immunotherapy.
Disclosure:
PF: nothing to disclose.
HPH: consulting fees and fees for serving on steering and data monitoring committees from Bayer Healthcare, Biogen, GeNeuro, Medimmune, Merck, Novartis, Receptos / Celgene, Roche, Sanofi Genzyme, Teva with approval by the Rector of Heinrich-Heine-University.
TO: has received lecture and/or advisory board honoraria from Biogen, Novartis, Genzyme, and Merck. The same companies have provided unrestricted MS research grants.
OA: accepted speakers honoraria and research funding from Biogen.
CW: consulting and/or research funding: Biogen, Novartis, Teva.
Study support: grant of the European Charcot Foundation and the Hertie-Foundation to CW (P1150063).

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