Ontogeny of the plasma proteome during the first week of life

Introduction: Early life is increasingly recognized as a major determinant for the development of the immune system and the overall health for the entire human lifespan. However, knowledge of the molecular drivers involved in these processes in newborns is fragmentary at best. This limits the success of preventative, diagnostic, and therapeutic interventions, especially for newborns where death caused by infections are most common, due to an immature immune system. Method: Blood plasma samples were collected from 30 newborns in Gambia at the day of birth and at a follow-up visit (Table). A similar cohort was collected in Papua New Guinea for validation. We characterized the plasma-proteome using one μL plasma. In brief, the samples were prepared in a 96-well format, and the generated peptides were analyzed on a Q Exactive (Thermo) mass spectrometer using a 45 min gradient per sample. Results: Cumulated, we identified 684 proteins in the 60 plasma samples (FDR<1%). Comparing day 1, 3, and 7 to day 0, we identified 10, 19, and 41 proteins with a statistically significantly changed plasma-concentration, respectively. As expected haptoglobin (HP) was increased, and already from day 1. The concentration of proteins involved in the innate immune system, e.g. complement, showed significant changes within 24 hours of birth. The concentration of maternally transferred IgG-antibodies, decreased after day 7, whereas native IgM-production increased. Conclusion: Significant and consistent changes related to ontogeny can be detected in the newborn plasma proteome during the first week of life. Within the first week of life, both the innate and adaptive immune system undergoes significant development.