Early-life infections, medications, and atopic sensitization in the development of immune-mediated diseases in Finland, Estonia, and Russian Karelia

• Main Author: Mustonen, Neea
• Other Authors: University of Helsinki, Faculty of Medicine, Research Program for Clinical and Molecular Metabolism, Doctoral Program in Clinical Research, Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsingin yliopisto, lääketieteellinen tiedekunta, Kliininen tohtoriohjelma, Helsingfors universitet, medicinska fakulteten, Doktorandprogrammet i klinisk forskning, Almqvist Malmros, Catarina, Knip, Mikael, Siljander, Heli
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Helsingin yliopisto 2020
• Subjects: lääketieteellinen tiedekunta; karelia*; karelian
• Online Access: http://hdl.handle.net/10138/320993

Background: The incidence of immune-mediated diseases, such as type 1 diabetes (T1D), celiac disease (CD), and allergic diseases, has been increasing since the 1950s. This trend has been particularly conspicuous in affluent Westernized countries. Etiologies behind these diseases are still poorly understood, but socioeconomic circumstances and environmental factors may play a crucial role in their pathomechanisms. The hygiene hypothesis aims to explain the rising trend in immune-mediated diseases by suggesting that children’s developing immune systems are vulnerable to malfunction in environments that provide inadequate microbial exposure early in life. Aims: This thesis aims to explore how early clinical infections, their medications, and allergic sensitization associate with the development of T1D, CD, and allergies in three geographically close areas in Finland, Estonia, and Russian Karelia. These neighboring countries have shown clear contrasts in the frequencies of immune-mediated diseases, standards of hygiene, and socioeconomic circumstances. Methods: As part of the DIABIMMUNE study, over 4500 children from Finland, Estonia, and Russian Karelia were prospectively followed either from birth to 3 years of age or from 3 to 5 years of age. Children attended regular clinical visits that comprised physical examinations and the collection of biological samples for the assessment of immune-mediated outcomes. Children’s parents prospectively reported all participating children’s illnesses, infections, medications, and allergic symptoms that appeared during the follow-up. Results: Regarding infectious illnesses, respiratory infections were most frequently reported, followed by gastrointestinal infections, unlocalized febrile episodes, and other localized infections. Compared to Russian Karelian and Estonian children, Finnish children experienced more infections and used more medications. Finnish children also had the highest frequency of T1D, CD, and allergic sensitization. In all, progression to T1D was associated ...