Soluble CD64 Is a Novel Marker of Steroid Refractory Acute Gastrointestinal Graft Versus Host Disease in Pediatric Allogeneic Hematopoietic Stem Cell Transplant

Abstract

Background CD64 is expressed on neutrophils and monocytes and is upregulated by mediators of inflammation such as interferon-gamma, G-CSF, infection or tissue injury. Soluble CD64 is elevated in new onset Crohn's disease and is a marker of intestinal inflammation. In Crohn's disease, elevated surface expression of CD64 has been associated with infliximab loss of response. The role of CD64 is not described in pediatric gastrointestinal graft versus host disease (GI GVHD). We hypothesized that CD64 would be elevated at diagnosis in children with acute GI GVHD at diagnosis. Methods Plasma CD64 was measured by ELISA in 40 patients (GI GVHD n=20, No GVHD n=20) at the following time points: before BMT and at diagnosis of acute GVHD or a comparable time point after BMT in controls (∼ day+35). Values were compared to new onset pediatric Crohn's disease (n=47) and non-inflammatory bowel disease (IBD) pediatric controls (n=42). Neutrophil CD64, measured by flow cytometry, was assessed in an independent group of 27 consecutive pediatric allogeneic BMT patients at diagnosis of GVHD or comparable time points in patients without GVHD. Results Patient demographics are shown in Table 1. Soluble CD64 was elevated in patients with GI GVHD at diagnosis compared to transplant patients without GVHD (p=0.003), Crohn's disease (p Nine of the 27 patients in the independent consecutive patient cohort had acute GVHD. Four patients had GI GVHD, 3 steroid refractory and one responsive. Median CD64 expression on neutrophils by flow cytometry was 14.3% in the GI GVHD patients compared to 4.92% in patients without GVHD (p=0.2) (Figure 2). Conclusion CD64 is a novel biomarker which could portend refractory acute gut GVHD in children. These findings need to be validated in a larger independent cohort.