Blood CD9+ B cell, a biomarker of bronchiolitis obliterans syndrome after lung transplantation

Am J Transplant. 2019 Nov;19(11):3162-3175. doi: 10.1111/ajt.15532. Epub 2019 Aug 21.

Abstract

Bronchiolitis obliterans syndrome is the main limitation for long-term survival after lung transplantation. Some specific B cell populations are associated with long-term graft acceptance. We aimed to monitor the B cell profile during early development of bronchiolitis obliterans syndrome after lung transplantation. The B cell longitudinal profile was analyzed in peripheral blood mononuclear cells from patients with bronchiolitis obliterans syndrome and patients who remained stable over 3 years of follow-up. CD24hi CD38hi transitional B cells were increased in stable patients only, and reached a peak 24 months after transplantation, whereas they remained unchanged in patients who developed a bronchiolitis obliterans syndrome. These CD24hi CD38hi transitional B cells specifically secrete IL-10 and express CD9. Thus, patients with a total CD9+ B cell frequency below 6.6% displayed significantly higher incidence of bronchiolitis obliterans syndrome (AUC = 0.836, PPV = 0.75, NPV = 1). These data are the first to associate IL-10-secreting CD24hi CD38hi transitional B cells expressing CD9 with better allograft outcome in lung transplant recipients. CD9-expressing B cells appear as a contributor to a favorable environment essential for the maintenance of long-term stable graft function and as a new predictive biomarker of bronchiolitis obliterans syndrome-free survival.

Keywords: B cell biology; basic (laboratory) research/science; biomarker; bronchiolitis obliterans (BOS); lung transplantation/pulmonology; translational research/science.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B-Lymphocytes / metabolism*
  • Biomarkers / metabolism*
  • Bronchiolitis Obliterans / diagnosis*
  • Bronchiolitis Obliterans / etiology
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Graft Rejection / diagnosis*
  • Graft Rejection / etiology
  • Graft Survival
  • Humans
  • Leukocytes, Mononuclear
  • Lung Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications / diagnosis*
  • Postoperative Complications / etiology
  • Prognosis
  • Risk Factors
  • Survival Rate
  • Syndrome
  • Tetraspanin 29 / metabolism*
  • Transplantation, Homologous
  • Young Adult

Substances

  • Biomarkers
  • CD9 protein, human
  • Tetraspanin 29