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Antibodies to Influenza Virus A/H1N1 Hemagglutinin in Type 1 Diabetes Children Diagnosed Before,During and After the SWEDISH A(H1N1)pdm09 Vaccination Campaign 2009–2010
Authors:M. Svensson,A. Ramelius,A.‐L. Nilsson,A. J. Delli,H. Elding Larsson,A. Carlsson,G. Forsander,S. A. Ivarsson,J. Ludvigsson,I. Kockum,C. Marcus,U. Samuelsson,E.   rtqvist,   . Lernmark
Affiliation:1. Department of Clinical Sciences Malm?, Sk?ne University Hospital SUS, Lund University, , Malm?, Sweden;2. Pediatric Clinic, ?stersund Hospital, , ?stersund, Sweden;3. Department of Clinical Sciences Lund, Sk?ne University Hospital SUS, Lund University, , Lund, Sweden;4. Department of Pediatrics, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, , Gothenburg, Sweden;5. Division of Pediatrics, Department of Clinical and Experimental Medicine, Link?ping University, , Link?ping, Sweden;6. Department of Clinical Neuroscience, Karolinska Institute, , Stockholm, Sweden;7. Division of Pediatrics, Department of Clinical Science, Intervention and Technology Karolinska Institute, , Stockholm, Sweden;8. Division of Pediatrics and Diabetes Research Center, Link?ping University Hospital, , Link?ping, Sweden;9. Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, , Stockholm, Sweden
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 35S‐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 (< 0.0001). In children <3 years 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 (= 0.006) and 13 < 18 (= 0.001), but not among the 6 < 13‐year‐olds. HLA‐DQ2/8 positive children <3 years decreased from 54% (15/28) before and 68% (19/28) during, to 30% (9/30) after vaccination (= 0.014). Regardless of age, DQ2/2; 2/X (n = 177) patients had lower frequency (= 0.020) and levels (= 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 (= 0.009). ZnT8QA frequency increased from 30% before to 34% during and 41% after vaccination (= 0.002). Our findings suggest that young (<3 years) along with DQ2/2; 2/X patients were low responders to Pandemrix®. As the proportion of DQ2/8 patients <3 years 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.
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