Reduction in White Blood Cell, Neutrophil, and Red Blood Cell Counts Related to Sex, HLA, and Islet Autoantibodies in Swedish TEDDY Children at Increased Risk for Type 1 Diabetes
Authors: Salami Falastin , Lee Hye-Seung , Freyhult Eva , Elding Larsson Helena , Lernmark Åke , Törn Carina ,   The TEDDY Study Group, Rewers Marian , Bautista Kimberly , Baxter Judith , Felipe-Morales Daniel , Driscoll Kimberly , Frohnert Brigitte I. , Gallant Marisa , Gesualdo Patricia , Hoffman Michelle , Karban Rachel , Liu Edwin , Norris Jill , Samper-Imaz Adela , Steck Andrea , Waugh Kathleen , Wright Hali , Toppari Jorma , Simell Olli G. , Adamsson Annika , Ahonen Suvi , Hyöty Heikki , Ilonen Jorma , Jokipuu Sanna , Karlsson Leena , Kähönen Miia , Knip Mikael , Koreasalo Mirva , Kurppa Kalle , Latva-aho Tiina , Lönnrot Maria , Mattila Markus , Mäntymäki Elina , Multasuo Katja , Niininen Tiina , Niinistö Sari , Nyblom Mia , Ollikainen Paula , Rajala Petra , Rautanen Jenna , Riikonen Anne , Romo Minna , Ruohonen Suvi , Rönkä Juulia , Simell Satu , Simell Tuula , Sjöberg Maija , Stenius Aino , Vainionpää Sini , Varjonen Eeva , Veijola Riitta , Virtanen Suvi M. , Vähä-Mäkilä Mari , Åkerlund Mari , Lindfors Katri , She Jin-Xiong , Schatz Desmond , Hopkins Diane , Steed Leigh , Bryant Jennifer , Adams Janey , Silvis Katherine , Haller Michael , Gardiner Melissa , McIndoe Richard , Sharma Ashok , Anderson Stephen W. , Jacobsen Laura , Marks John , Towe P.D. , Ziegler Anette G. , Beyerlein Andreas , Bonifacio Ezio , Gavrisan Anita , Gezginci Cigdem , Heublein Anja , Hummel Michael , Hummel Sandra , Knopff Annette , Koch Charlotte , Koletzko Sibylle , Ramminger Claudia , Roth Roswith , Scholz Marlon , Stock Joanna , Warncke Katharina , Wendel Lorena , Winkler Christiane , Lernmark Åke , Agardh Daniel , Aronsson Carin Andrén , Ask Maria , Bremer Jenny , Carlsson Ulla-Marie , Cilio Corrado , Ericson-Hallström Emelie , Fors Annika , Fransson Lina , Gard Thomas , Bennet Rasmus , Hansson Carina , Hyberg Susanne , Jisser Hanna , Johansen Fredrik , Jonsdottir Berglind , Jovic Silvija , Elding Larsson Helena , Lindström Marielle , Lundgren Markus , Månsson-Martinez Maria , Markan Maria , Melin Jessica , Mestan Zeliha , Nilsson Caroline , Ottosson Karin , Rahmati Kobra , Ramelius Anita , Salami Falastin , Sibthorpe Sara , Sjöberg Anette , Sjöberg Birgitta , Törn Carina , Wallin Anne , Wimar Åsa , Åberg Sofie , Hagopian William A. , Killian Michael , Crouch Claire Cowen , Skidmore Jennifer , Akramoff Ashley , Banjanin Jana , Chavoshi Masumeh , Dunson Kayleen , Hervey Rachel , Lyons Rachel , Meyer Arlene , Mulenga Denise , Radtke Jared , Schmitt Davey , Schwabe Julie , Zink Sarah , Becker Dorothy , Franciscus Margaret , Dalmagro-Elias Smith MaryEllen , Daftary Ashi , Klein Mary Beth , Yates Chrystal , Krischer Jeffrey P. , Austin-Gonzalez Sarah , Avendano Maryouri , Baethke Sandra , Brown Rasheedah , Burkhardt Brant , Butterworth Martha , Clasen Joanna , Cuthbertson David , Eberhard Christopher , Fiske Steven , Garcia Dena , Garmeson Jennifer , Gowda Veena , Heyman Kathleen , Hsiao Belinda , Laras Francisco Perez , Lee Hye-Seung , Liu Shu , Liu Xiang , Lynch Kristian , Maguire Colleen , Malloy Jamie , McCarthy Cristina , Merrell Aubrie , Meulemans Steven , Parikh Hemang , Quigley Ryan , Remedios Cassandra , Shaffer Chris , Smith Laura , Smith Susan , Sulman Noah , Tamura Roy , Toth Michael , Uusitalo Ulla , Vehik Kendra , Vijayakandipan Ponni , Wood Keith , Yang Jimin , Yu Liping , Miao Dongmei , Bingley Polly , Williams Alistair , Chandler Kyla , Ball Olivia , Kelland Ilana , Grace Sian , Gillard Ben , Hagopian William , Chavoshi Masumeh , Radtke Jared , Schwabe Julie , Erlich Henry , Mack Steven J. , Fear Anna Lisa , Ke Sandra , Mulholland Niveen , Akolkar Beena , Bourcier Kasia , Briese Thomas , Johnson Suzanne Bennett , Triplett Eric 
Published: August 2018

Islet autoantibodies (IAs) precede the clinical onset of type 1 diabetes (T1D); however, the knowledge is limited about whether the prodrome affects complete blood counts (CBCs) in 4- to 12-year-old children with increased genetic risk for T1D. This study tested whether CBCs were altered in 4- to 12-year-old children without (n = 376) or with one or several IAs against insulin, GAD65, or IA-2 (n = 72). CBC was analyzed during longitudinal follow-up in 448 Swedish children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A linear mixed-effects model was used to assess potential association between IA and CBC measurements over time. The white blood cell and neutrophil counts were reduced in children with IAs, primarily in boys. In contrast, girls had lower levels of hemoglobin and hematocrit. Positivity for multiple IAs showed the lowest counts in white blood cells and neutrophils in boys and red blood cells, hemoglobin, and hematocrit in girls. These associations were primarily observed in children with the HLA-DR3-DQ2/DR4-DQ8 genotype. We conclude that the reduction in neutrophils and red blood cells in children with multiple IAs and HLA-DR3-DQ2/DR4-DQ8 genotype may signal a sex-dependent islet autoimmunity detected in longitudinal CBCs.