Antibodies to Influenza VirusA/H1N1 Hemagglutinin in Type 1 Diabetes Children Diagnosed Before, During and After the SWEDISHA(H1N1)pdm09 Vaccination Campaign 2009–2010

Abstract

We determined A/H1N1-hemagglutinin (HA) antibodies in relation to HLA-DQ genotypes and islet autoantibodies at clinical diagnosis in 1141 incident 0.7-to 18-year-old type 1 diabetes patients diagnosed April 2009-December 2010. Antibodies to (35) S-methionine-labelled A/H1N1 hemagglutinin were determined in a radiobinding assay in patients diagnosed before (n=325), during (n=355) and after (n=461) the October 2009-March 2010 Swedish A(H1N1)pdm09 vaccination campaign, along with HLA-DQ genotypes and autoantibodies against GAD, insulin, IA-2 and ZnT8 transporter. Before vaccination, 0.6% patients had A/H1N1-HA antibodies compared with 40% during and 27% after vaccination (P<0.0001). In children <3years of age, A/H1N1-HA antibodies were found only during vaccination. The frequency of A/H1N1-HA antibodies during vaccination decreased after vaccination among the 3<6 (P=0.006) and 13<18 (P=0.001), but not among the 6<13-year-olds. HLA-DQ2/8 positive children <3years decreased from 54% (15/28) before and 68% (19/28) during, to 30% (9/30) after vaccination (P=0.014). Regardless of age, DQ2/2; 2/X (n=177) patients had lower frequency (P=0.020) and levels (P=0.042) of A/H1N1-HA antibodies compared with non-DQ2/2; 2/X (n=964) patients. GADA frequency was 50% before, 60% during and 51% after vaccination (P=0.009). ZnT8QA frequency increased from 30% before to 34% during and 41% after vaccination (P=0.002). Our findings suggest that young (<3years) along with DQ2/2; 2/X patients were low responders to Pandemrix(®) . As the proportion of DQ2/8 patients <3years of age decreased after vaccination and the frequencies of GADA and ZnT8QA were enhanced, it cannot be excluded that the vaccine affected clinical onset of type 1 diabetes.