학술논문
Joint modeling of longitudinal autoantibody patterns and progression to type 1 diabetes: results from the TEDDY study
Document Type
Original Paper
Author
Köhler, Meike; Beyerlein, Andreas; Vehik, Kendra; Greven, Sonja; Umlauf, Nikolaus; Lernmark, Åke; Hagopian, William A.; Rewers, Marian; She, Jin-Xiong; Toppari, Jorma; Akolkar, Beena; Krischer, Jeffrey P.; Bonifacio, Ezio; Ziegler, Anette-G.; Rewers, Marian; Bautista, Kimberly; Baxter, Judith; Bedoy, Ruth; Felipe-Morales, Daniel; Driscoll, Kimberly; Frohnert, Brigitte I.; 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; Kallio, Tiina; Karlsson, Leena; Kähönen, Miia; Knip, Mikael; Kovanen, Lea; Koreasalo, Mirva; Kurppa, Kalle; Latva-aho, Tiina; Lönnrot, Maria; Mäntymäki, Elina; Multasuo, Katja; Mykkänen, Juha; Niininen, Tiina; Niinistö, Sari; Nyblom, Mia; Rajala, Petra; Rautanen, Jenna; Riikonen, Anne; Riikonen, Mika; Rouhiainen, Jenni; Romo, Minna; Simell, Tuula; Simell, Ville; Sjöberg, Maija; Stenius, Aino; Leppänen, Maria; 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; Thomas, Jamie; Adams, Janey; Silvis, Katherine; Haller, Michael; Gardiner, Melissa; McIndoe, Richard; Sharma, Ashok; Williams, Joshua; Young, Gabriela; Anderson, Stephen W.; Jacobsen, Laura; Ziegler, Anette G.; Beyerlein, Andreas; Bonifacio, Ezio; Hummel, Michael; Hummel, Sandra; Foterek, Kristina; Janz, Nicole; Kersting, Mathilde; Knopff, Annette; Koletzko, Sibylle; Peplow, 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; Fransson, Lina; Gard, Thomas; Gerardsson, Joanna; Bennet, Rasmus; Hansen, Monica; Hansson, Gertie; Hyberg, Susanne; Johansen, Fredrik; Jonsdottir, Berglind; Larsson, Helena Elding; Lindström, Marielle; Lundgren, Markus; Månsson-Martinez, Maria; Markan, Maria; Melin, Jessica; Mestan, Zeliha; Ottosson, Karin; Rahmati, Kobra; Ramelius, Anita; Salami, Falastin; Sibthorpe, Sara; Sjöberg, Birgitta; Swartling, Ulrica; Amboh, Evelyn Tekum; Törn, Carina; Wallin, Anne; Wimar, Åsa; Åberg, Sofie; Hagopian, William A.; Killian, Michael; Crouch, Claire Cowen; Skidmore, Jennifer; Carson, Josephine; Dalzell, Maria; Dunson, Kayleen; Hervey, Rachel; Johnson, Corbin; Lyons, Rachel; Meyer, Arlene; Mulenga, Denise; Tarr, Alexander; Uland, Morgan; Willis, John; Becker, Dorothy; Franciscus, Margaret; Smith, MaryEllen Dalmagro-Elias; Daftary, Ashi; Klein, Mary Beth; Yates, Chrystal; Krischer, Jeffrey P.; Abbondondolo, Michael; 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; PerezLaras, Francisco; Lee, Hye-Seung; Liu, Shu; Liu, Xiang; Lynch, Kristian; Malloy, Jamie; McCarthy, Cristina; Meulemans, Steven; Parikh, Hemang; Shaffer, Chris; Smith, Laura; Smith, Susan; Sulman, Noah; Tamura, Roy; Uusitalo, Ulla; Vehik, Kendra; Vijayakandipan, Ponni; Wood, Keith; Yang, Jimin; Ballard, Lori; Hadley, David; McLeod, Wendy; Akolkar, Beena; Yu, Liping; Miao, Dongmei; Bingley, Polly; Williams, Alistair; Chandler, Kyla; Rokni, Saba; Williams, Claire; Wyatt, Rebecca; George, Gifty; Grace, Sian; Erlich, Henry; Mack, Steven J.; Ke, Sandra; Mulholland, Niveen; Bourcier, Kasia; Briese, Thomas; Johnson, Suzanne Bennett; Triplett, Eric; TEDDY study group; Ancillary Studies; Diet; Genetics; Human Subjects/Publicity/Publications; Immune Markers; Infectious Agents; Laboratory Implementation; Maternal Studies; Psychosocial; Quality Assurance; Steering; Study Coordinators; Celiac Disease; Clinical Implementation; Quality Assurance Subcommittee on Data Quality
Source
Acta Diabetologica. :1-9
Subject
Language
English
ISSN
0940-5429
1432-5233
1432-5233
Abstract
Aims:The onset of clinical type 1 diabetes (T1D) is preceded by the occurrence of disease-specific autoantibodies. The level of autoantibody titers is known to be associated with progression time from the first emergence of autoantibodies to the onset of clinical symptoms, but detailed analyses of this complex relationship are lacking. We aimed to fill this gap by applying advanced statistical models.Methods:We investigated data of 613 children from the prospective TEDDY study who were persistent positive for IAA, GADA and/or IA2A autoantibodies. We used a novel approach of Bayesian joint modeling of longitudinal and survival data to assess the potentially time- and covariate-dependent association between the longitudinal autoantibody titers and progression time to T1D.Results:For all autoantibodies we observed a positive association between the titers and the T1D progression risk. This association was estimated as time-constant for IA2A, but decreased over time for IAA and GADA. For example the hazard ratio [95% credibility interval] for IAA (per transformed unit) was 3.38 [2.66, 4.38] at 6 months after seroconversion, and 2.02 [1.55, 2.68] at 36 months after seroconversion.Conclusions:These findings indicate that T1D progression risk stratification based on autoantibody titers should focus on time points early after seroconversion. Joint modeling techniques allow for new insights into these associations.