Fecal calprotectin and alpha-1 antitrypsin predict severity and response to corticosteroids in gastrointestinal graft-versus-host disease

Abstract

<jats:title>Abstract</jats:title><jats:p>Diagnosis of gastrointestinal GVHD (GI-GVHD) is based on clinical symptoms and histologic findings. No biomarkers predicting responses to treatment are routinely available even though 30% to 50% of patients will not respond to corticosteroids. In this study, we aimed to evaluate fecal calprotectin, α-1-antitrypsin (α1-AT), and elastase at the time of first symptoms as diagnostic and prognostic tools for GI-GVHD in 72 consecutive patients, of whom 51 developed GI-GVHD. The prognostic value of markers was evaluated by their association with complete response (CR) and steroid-resistant (SR) GVHD. Calprotectin and α1-AT concentrations increased with GI-GVHD initial stages but patients with initial stage 1 GI-GVHD had similar marker levels to patients without GI-GVHD, so sensitivity to diagnose GI-GVHD was weak. In contrast, calprotectin and α1-AT were predictors for SR-GVHD and CR. Multiple regression modeling identified calprotectin and α1-AT concentration as independently predicting SR-GVHD together with initial stage &gt; 2 GI-GVHD. Our results showed that fecal calprotectin and α1-AT levels at the time of diagnosis are predictive for responses to treatment but are not diagnostic markers for initial stage 1 to 3 GI-GVHD.</jats:p>

Plasma biomarkers of acute GVHD and nonrelapse mortality: predictive value of measurements before GVHD onset and treatment

“…3,19 Other potential prognostic markers of gastrointestinal GVHD at the time of initial diagnosis include fecal samples (for calprotectin and a-1-antitrypsin), falling serum albumin as a reflection of gut protein loss, endoscopic appearance, specific histologic changes, and circulating angiogenic factors. 10,13,[20][21][22][23] Reconciling results of studies predicting the outcome of GVHD based on clinical parameters, plasma and fecal samples, and mucosal histology-done at different centers-is difficult, because there are differences in timing, handling of specimens, storage time, analytical techniques, choice of biomarkers, and statistical methods. It is also not clear whether prognostic markers for gastrointestinal GVHD will vary with the intensity of conditioning therapy, choice of GVHD prophylaxis, and source of hematopoietic cells.…”

Biomarkers for acute GVHD: can we predict the unpredictable?

“…46 In addition, investigators from France recently reported in a smaller study on the prognostic value of measuring fecal concentrations of calprotectin and a1-antitrypsin at diagnosis of intestinal GVHD. 47 Although not being able to distinguish between other GI maladies, these widely available stool protein assays can potentially assist in stratifying risk. Further validation in different populations is required, but progress is certainly being made towards a risk-adapted clinical trial for the initial therapy of acute GVHD (see Figure 1a).…”

Fecal calprotectin and α1-antitrypsin dynamics in gastrointestinal GvHD

“…15 Here, we studied the dynamics of calprotectin and α1-AT from GI-GvHD onset to last symptoms for a correlation between marker evolution and GI-GvHD symptoms.…”

“…As described in detail in our previous study, 15 stool samples were gathered in plastic containers and dispatched to the laboratory within 48 h. Fecal α1-AT measurement was determined immediately using immunonephelometry on the BN ProSpec system (Siemens SAS, Saint-Denis, France) and reported per gram dry weight of stools. The measurement range was between 0.01 and 20 mg/g dry weight, and the upper normal limit was set at 1.5 mg/g dry weight.…”

“…14 In the context of gastrointestinal GvHD (GI-GvHD), calprotectin and α1-AT levels were found to be elevated and to predict the response to corticosteroids. [15][16][17] Although fecal testing is noninvasive and easily available, sensitivity and specificity are too low to replace conventional diagnostic tools-that is, histology. 18 Acute GvHD can manifest in the skin, the liver and the gut, either sequentially, simultaneously in the skin and gut, or in a single organ such as the skin, but all as the result of a systemic process.…”