Auto-inflammation and auto-immunity pathways are associated with emergence of BOS in pediatric lung transplantation

Carol K. Conrad, Haley Hedlin, Hyunsook Chin, Don Hayes, Peter S. Heeger, Albert Faro, Samuel Goldfarb, Ernestina Melicoff-Portillo, Mohanakumar Thalachallour, Jonah Odim, Marc Schecter, Gregory A. Storch, Gary A. Visner, Nikki M. Williams, Karen Kesler, Lara Danziger-Isakov, Stuart C. Sweet

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Long-term survival after lung transplantation (LTx) is limited by chronic lung allograft dysfunction (CLAD).

METHODS: We report an analysis of cytokine profiles in bronchoalveolar lavage samples collected during a prospective multicenter non-interventional trial primarily designed to determine the impact of community-acquired respiratory viral infections (CARV) in outcomes after pediatric LTx. In this analysis, we identify potential biomarkers of auto-inflammation and auto-immunity associated with survival and risk of bronchiolitis obliterans (BOS) after LTx with cytokine analysis of bronchoalveolar lavage fluid (BALF) from 61 pediatric recipients.

RESULTS: Higher IL-23 (p = .048) and IL-31 (p = .035) levels were associated with the risk of BOS, and lower levels of epithelial growth factor (EGF) (p = .041) and eotaxin (EOX) (p = .017) were associated with BOS. Analysis using conditional inference trees to evaluate cytokines at each visit associated with survival identified soluble CD30 (p < .001), pro-inflammatory cytokine IL-23 (p = .02), and sTNFRI (p = .01) below cutoff levels as associated with BOS-free survival.

CONCLUSIONS: Our results indicate that post-LTx survival in children may be linked to activation of alternate pathways of the immune system that affect airway remodeling in addition to activation of "classical" pathways that have been described in adult LTx recipients. These may indicate pathways to target for intervention.

Original languageEnglish (US)
Article numbere14247
JournalPediatric transplantation
Issue number4
StatePublished - Jun 2022

Bibliographical note

Funding Information:
This research was performed under the auspices and guidance of the Clinical Trials in Organ Transplantation in Children, a collaborative clinical research project headquartered at the National Institute of Allergy and Infectious Diseases, supported by Grant U01 AI077810 “Viral Triggers of Alloimmunity and Autoimmunity in Pediatric Lung Transplantation” from the Division of Allergy, Immunology and Transplantation of the National Institutes of Health.

Funding Information:
The cytokine analysis was independently funded by the Arline and Pete Harmon Scholarhsip in Pediatric Pulmonary Biology at Stanford University awarded to Dr. Carol Conrad. For the CTOTC study—National Institute of Allergy and Infectious Diseases, Grant/Award Number: U01AI077810/AI/NIAID NIH HHS/United States. UM2 AI117870/AI/NIAID NIH HHS/United States. For analysis of the cytokines—Arline and Pete Harman Faculty Scholar in Pediatric Pulmonary Biology. This study was approved by the IRB of Stanford University H H

Publisher Copyright:
© 2022 Wiley Periodicals LLC.


  • auto-inflammation
  • BOS
  • CLAD
  • pediatric lung transplant
  • Prospective Studies
  • Humans
  • Interleukin-23
  • Inflammation
  • Lung Transplantation
  • Bronchiolitis Obliterans/diagnosis
  • Adult
  • Cytokines/metabolism
  • Child

PubMed: MeSH publication types

  • Journal Article
  • Multicenter Study


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