Increased Mac-2 binding protein glycan isomer in patients at risk for late nonrelapse mortality after HSCT

Abstract

Abstract: Macrophages play a crucial role in the pathogenesis of chronic graft-versus-host disease (cGVHD). We hypothesized that galectin-3, Mac-2 binding protein (M2BP), or Wisteria floribunda agglutinin (WFA)+-M2BP, called M2BP glycan isomer (M2BPGi), might contribute to macrophage activation, and fibrosis would be associated with cGVHD and nonrelapse mortality (NRM) in hematopoietic stem cell transplant (HSCT) recipients. Patients who underwent their first allogeneic HSCT and survived for >180 days without relapse were included. The predictive potential of the 3 markers for NRM was assessed using the discovery cohort (n = 55) and validation cohort 1 (n = 55). When we used the threshold determined by a receiver operating characteristics curve analysis in the discovery cohort, only M2BPGi at day +180 was significantly associated with a higher NRM in the discovery cohort (15.0% vs 0.0% at 5 years, P = .001) and in validation cohort 1 (34.0% vs 8.4% at 5 years, P = .014). This result was confirmed in validation cohort 2 (n = 50). M2BPGi was not increased in healthy individuals or in patients who received autologous HSCT. In the entire cohort (N = 110), M2BPGi was significantly related to liver cGVHD but not to other organ involvement. In multivariate analyses, M2BPGi was an independent risk factor for NRM. In immunofluorescence staining of autopsy cases, WFA+-M2BP–positive macrophages were found only in the liver sections with cGVHD. In conclusion, M2BPGi could be a promising predictor of late NRM after HSCT and was associated with liver involvement.