Calprotectin Expressing Donor-Derived Macrophages Increase in Acute Gastrointestinal Graft-Versus-Host Disease

Transplant Cell Ther. 2022 May;28(5):248.e1-248.e8. doi: 10.1016/j.jtct.2022.01.028. Epub 2022 Feb 8.


Acute graft versus host disease (GVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). GVHD is therefore the main obstacle for a more widespread use of this highly effective and potentially curative therapy. Although donor T cells are believed to be key mediators in the pathogenesis of acute GVHD, recent reports have suggested that monocyte-derived macrophages also contribute. However, data to support a role for macrophages in acute GVHD in the gastrointestinal tract are sparse. Here we performed a spatiotemporal in situ study to determine the presence of donor and recipient macrophage subsets in colon biopsies from allo-HSCT patients with and without GVHD. Our study was a retrospective study examining colon biopsies from 31 allo-HSCT patients (10 females), of which 21 (5 females) had clinical and histologically-verified GVHD. To distinguish host from donor macrophages we examined gender mismatched donors applying a combination of immunostaining and fluorescence in situ hybridization with probes to X and Y chromosomes. The density of colonic mucosal macrophages was significantly increased (P = .0031) in patients with acute GVHD (n = 21) compared with patients without GVHD (n = 10). Most macrophages were of donor origin in both groups; however, in acute GVHD there was a fivefold increase in donor-derived macrophages expressing the antimicrobial protein calprotectin; reminiscent of recently emigrated proinflammatory monocytes. Moreover, colonic macrophages were found in close proximity to both host and donor T cells. Together, our results suggest that donor-derived proinflammatory macrophages are involved in the immunopathology of colonic acute GHVD in humans.

Keywords: Acute graft versus host disease (GVHD); Allogeneic stem cell transplantation (allo-HSCT); Macrophages; Monocytes.

MeSH terms

  • Colon / metabolism
  • Female
  • Graft vs Host Disease* / etiology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukocyte L1 Antigen Complex
  • Macrophages / metabolism
  • Male
  • Retrospective Studies


  • Leukocyte L1 Antigen Complex