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 Jr; 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

doi:10.1111/petr.14247

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

Pediatr Transplant. 2022 Jun;26(4):e14247. doi: 10.1111/petr.14247. Epub 2022 Feb 10.

Authors

Carol K Conrad¹, Haley Hedlin², Hyunsook Chin³, Don Hayes Jr⁴, Peter S Heeger⁵, Albert Faro⁶, Samuel Goldfarb⁷, Ernestina Melicoff-Portillo⁸, Mohanakumar Thalachallour⁹, Jonah Odim¹⁰, Marc Schecter¹¹, Gregory A Storch¹², Gary A Visner¹³, Nikki M Williams¹⁰, Karen Kesler³, Lara Danziger-Isakov³, Stuart C Sweet¹¹

Affiliations

¹ Department of PediatricsStanford University School of Medicine, Palo Alto, California, USA.
² Quantitative Sciences Unit, Stanford University School of Medicine, Stanford, California, USA.
³ Rho Federal Systems, Durham, North Carolina, USA.
⁴ Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁵ Department of Medicine, Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶ Cystic Fibrosis Foundation, Bethesda, Maryland, USA.
⁷ Masonic Children's Hospital, University of Minnesota, Minneapolis, Minnesota, USA.
⁸ Texas Children's Hospital, Houston, Texas, USA.
⁹ Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
¹⁰ National Institutes of Health, NIAID, Bethesda, Maryland, USA.
¹¹ University of Florida, Gainsville, Florida, USA.
¹² Washington University School of Medicine, St. Louis, Missouri, USA.
¹³ Boston Children's Hospital, Boston, Massachusetts, USA.

Abstract

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.

Keywords: BOS; CLAD; auto-inflammation; pediatric lung transplant.

Publication types

Multicenter Study

MeSH terms

Adult
Bronchiolitis Obliterans* / diagnosis
Bronchiolitis Obliterans* / etiology
Child
Cytokines / metabolism
Humans
Inflammation
Interleukin-23
Lung Transplantation*
Prospective Studies

Substances

Cytokines
Interleukin-23

Abstract

Publication types

MeSH terms

Substances

Grants and funding