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Evidence for B cell maturation but not trained immunity in uninfected infants exposed to hepatitis C virus
  1. Anton Lutckii1,2,
  2. Benedikt Strunz3,
  3. Anton Zhirkov2,
  4. Olga Filipovich4,
  5. Elena Rukoiatkina5,6,
  6. Denis Gusev7,
  7. Yuriy Lobzin2,
  8. Björn Fischler8,9,
  9. Soo Aleman10,11,
  10. Matti Sällberg1,
  11. Niklas K Björkström3
  1. 1 Department of Laboratory Medicine, Karolinska institutet, Stockholm, Sweden
  2. 2 Pediatric Research and Clinical Center for Infectious Diseases, Saint Petersburg, Russian Federation
  3. 3 Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  4. 4 North-Western State Medical University named after I.I.Mechnikov, Saint Petersburg, Russian Federation
  5. 5 Maternity Hospital No 16, Saint Petersburg, Russian Federation
  6. 6 Department of Pediatrics, Gynecology and Female Reproductology, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russian Federation
  7. 7 Center for Prevention and Control of AIDS and Infectious Diseases, Saint Petersburg, Russian Federation
  8. 8 Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
  9. 9 Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden
  10. 10 Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
  11. 11 Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to Dr Niklas K Björkström, Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm 14186, Sweden; niklas.bjorkstrom{at}


Objectives Vertical transmission of hepatitis C virus (HCV) is rare compared with other chronic viral infections, despite that newborns have an immature, and possibly more susceptible, immune system. It further remains unclear to what extent prenatal and perinatal exposure to HCV affects immune system development in neonates.

Design To address this, we studied B cells, innate immune cells and soluble factors in a cohort of 62 children that were either unexposed, exposed uninfected or infected with HCV. Forty of these infants were followed longitudinally from birth up until 18 months of age.

Results As expected, evidence for B cell maturation was observed with increased age in children, whereas few age-related changes were noticed among innate immune cells. HCV-infected children had a high frequency of HCV-specific IgG-secreting B cells. Such a response was also detected in some exposed but uninfected children but not in uninfected controls. Consistent with this, both HCV-exposed uninfected and HCV-infected infants had evidence of early B cell immune maturation with an increased proportion of IgA-positive plasma cells and upregulated CD40 expression. In contrast, actual HCV viraemia, but not mere exposure, led to alterations within myeloid immune cell populations, natural killer (NK) cells and a distinct soluble factor profile with increased levels of inflammatory cytokines and chemokines.

Conclusion Our data reveal that exposure to, and infection with, HCV causes disparate effects on adaptive B cells and innate immune cell such as myeloid cells and NK cells in infants.

  • HCV
  • immune response
  • dendritic cells
  • cytokines
  • B cell

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  • Contributors All authors contributed to study concept, set up and design, as well as interpretation of data. AL and BS planned experiments, and acquired and analysed data. AZ, OF, SA, ER, DG, YL and BF contributed to subject enrolment, sample collection, project administration and supervision. MS and NKB supervised the study. AL and NKB drafted the manuscript. All authors contributed to critical revisions and approved the final version of the manuscript.

  • Funding This work was funded by the Swedish Research Council, the Swedish Cancer Society, the Swedish Foundation for Strategic Research, the Cancer Research Foundations of Radiumhemmet, Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation, the Center for Innovative Medicine at Karolinska Institutet, Region Stockholm, SRP Diabetes Karolinska Institutet and Karolinska Institutet.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol was approved by local ethical committees at RICI, Saint Petersburg, Russia, and by the Regional ethical board of Stockholm, Sweden.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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