Associations of ABO, D, and Lewis blood groups and HLA Class I and Class II alleles with West Nile virus Lineage 2 disease outcome in Greece, 2010 to 2013

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West Nile virus (WNV) infection, commonly asymptomatic, may cause mild West Nile fever (WNF) or potentially fatal neuroinvasive disease (WNND). An outbreak of 262 cases of the new Lineage 2 strain in Greece in 2010 continued with high mortality (17%) in WNND. The objective was to investigate ABO, D, and Lewis blood groups, as well as HLA Class I and Class II alleles, in relation to WNV Lineage 2 disease morbidity.


A cohort of 132 Greek WNV cases in 2010 to 2013 (65% male; mean age 64 years; 41% WNF, 59% WNND) was compared to 51,339 healthy WNV-negative blood donors and 246 healthy subjects.


Blood group A was more common in WNV cases (51%) than blood donors (39%) and group O less common (32% vs. 42%). D negativity within group A was higher in WNV than in blood donors (18% vs. 10%, p = 0.044). The frequency of secretors (Lewis(a–b+)) was 60% in WNV and 68% in donors (p = 0.16). HLA alleles C*08, DRB1*O4:O5, and DQB1*O2 occurred significantly less frequently in WNV than controls (p < 0.05 unadjusted for multiple testing) and DRB1*10:O1 more frequently (p = 0.039).


This first study of symptomatic WNV Lineage 2 suggests A/D negativity as a new risk factor associated with WNV infection and level of morbidity. Further studies are required of the possibility that HLA C*08, DRB1*O4:O5, and DQB1*O2 are protective alleles and DRB1*10:O1 a “susceptible” allele to WNV infection and the role of secretor status in relation to WNV infection.

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