Fecal calprotectin and α1-antitrypsin dynamics in gastrointestinal GvHD

Abstract

In a previous study, the fecal biomarkers calprotectin and α1-antitrypsin (α1-AT) at symptom onset were reported to be significantly associated with the response to steroids in gastrointestinal GvHD (GI-GvHD). The purpose of this trial was to evaluate the dynamics of the fecal biomarkers calprotectin and α1-AT throughout the course of GvHD. Patients who were refractory to steroids had initially higher biomarker levels and in the course of GvHD demonstrated a continuous increase in fecal biomarkers. In contrast, the dynamics of calprotectin and α1-AT demonstrated low and decreasing levels in cortico-sensitive GvHD. In steroid-refractory patients who received a second line of treatment, the biomarker levels at the beginning of second-line treatment did not predict the subsequent response. Nevertheless, calprotectin levels progressively decreased in subsequent responders, whereas non-responders demonstrated continuously high levels of calprotectin. α1-AT values correlated to a lesser extent with the response to second-line treatment and remained elevated in both non-responders and responders. In conclusion, calprotectin monitoring can be of use in the management of immunosuppressive treatment in GI-GvHD.

Danger Signals and Graft-versus-host Disease: Current Understanding and Future Perspectives

“…AAT also inhibits IL-32 activation mediated by proteinase-3, which is a neutrophil granule serine proteinase (169, 170). AAT homeostasis after allo-HCT may be important for regulating allogeneic responses because elevated AAT clearance in stool was correlated with the severity of GI-GVHD and steroid resistant GVHD (SR-GVHD) in some studies (171–173), but not others (174). Consistent with this, we and others have demonstrated that AAT treatment for SR-GVHD-improved GVHD manifestations without significant adverse effects or increased rates of infection in a multicenter prospective or single institution phase I/II study (175, 176).…”

Understanding Luminal Microorganisms and Their Potential Effectiveness in Treating Intestinal Inflammation

“…Those receiving FMT from a lean donor showed a significant improvement in peripheral insulin sensitivity(82). Another potential role for FMT may be GVHD following allogeneic HSCT, given the loss of bacterial diversity (83) and elevation of fecal inflammatory biomarkers (calprotectin and α1-antitrypsin) (84) seen in these patients. Indeed, loss of intestinal bacterial diversity has been shown to be an independent predictor for mortality in patients following allogeneic HSCT (85).…”

Fecal Calprotectin as a Diagnostic and Prognostic Biomarker for Gastrointestinal Graft Versus Host Disease: A Systematic Review of Literature

“…Graft versus host disease (GVHD) is the most important complication after allogeneic hematopoietic stem cell transplantation (HSCT) and a leading cause of morbidity and mortality [1-2]. The incidence of acute gastrointestinal graft versus host disease (GI-GVHD) in HSCT patients is reported to between 40% and 50% [3].…”

“…Calprotectin is released upon cell disruption and cell death. Its level in feces is found to be six times higher than in plasma, and it remains stable in stool for more than seven days at a different temperature, thereby showing resistance to proteolysis [2-3,6].…”