Evaluation of crypt apoptotic bodies and apoptotic indices in pediatric celiac disease by routine staining and H2AX immunostaining

Abstract

Celiac disease (CD) is an immune-mediated disorder with premature apoptosis occurring along the entire crypt-villous axis. H2AX is the end product of the intrinsic apoptotic pathway. This is the first study to assess apoptotic body counts (ABC) by H&E and apoptotic indices (AI) by immunohistochemistry (IHC) in pediatric CD. The aim of the current study was to evaluate ABC in pediatric patients with CD prior to and following institution of a gluten free diet (GFD). Sixty-three pediatric endoscopic duodenal samples were assessed and divided into three groups. A total of 21 samples from treatment naïve CD patients, 21 from the same patients after instituting a GFD, and 21 from non-celiac patients as a control group. Histopathological evaluation of ABC by H&E, and immunohistochemistry assessment of apoptotic indices (AI) by H2AX antibody were performed. The mean maximum ABC and AI were significantly higher in treatment naïve CD than in GFD and control samples. These values were also significantly higher in treatment naïve Marsh 3C (flat) than in Marsh 1, 2, 3A, and 3B (non-flat) CD cases. GFD samples with persistent flat lesions had significantly higher ABC and AI than GFD non-flat cases. ROC analysis of the mean maximum ABC and AI of treatment naïve CD cases had a statistically significant predictive potential for persistent villous atrophy at a cut-off level ⩾6.61 ( P = 0.008) and ⩾105.4 ( P = 0.003), respectively. Histopathological evaluation of crypt apoptotic bodies could provide predictive potential for continued villous atrophy following GFD.

Intraepithelial lymphocytes are associated with epithelial injury in feline intestinal T-cell lymphoma

“…Apoptotic intestinal epithelial cells are observed in human celiac disease patients [ 10 , 13 , 16 , 23 ]. In vitro studies have shown that intraepithelial lymphocytes extracted from patients with celiac disease induced epithelial cell apoptosis via GRB [ 9 , 12 ].…”

Apoptotic bodies: bioactive treasure left behind by the dying cells with robust diagnostic and therapeutic application potentials

“…An increased number of ApoBDs in histological tests for gastrointestinal biopsies indicates gastrointestinal damage [ 133 ]. Similarly, it has been reported that ApoBDs have potential in the diagnosis of celiac diseases because the number of ApoBDs in active celiac disease significantly increases [ 134 , 135 ]. Kawashima et al found typical ApoBDs in the cerebellar granular layer in Japanese patients with Creutzfeldt-Jakob disease, suggesting that the increase of ApoBDs in the cerebellar granular layer may be important for the disease diagnosis.…”

“…Drug sensitivity and toxicity of pancreatic tumor cells can also be assessed by impedance cytology of ApoBDs [ 137 ]. Some researchers have also proposed the use of crypt ApoBDs markers to detect graft-versus-host disease [ 135 , 138 , 139 ]. It has been suggested that the presence of 6 or fewer crypt ApoBDs is sufficient to diagnose graft-versus-host disease, but there is no conclusive evidence for this diagnosis [ 138 ].…”

Advances in biological functions and applications of apoptotic vesicles

“…Although the count of ApoBDs is considered a diagnostic criterion for GVHD and ACR, merely utilizing this index may not be sufficient and cannot accurately distinguish these diseases from the normal ileal mucosa [ 126 ]. Crypt ApoBDs can also be used to predict villous atrophy recovery after gluten-free diet treatment in celiac disease [ 127 , 128 ]. Furthermore, the count of portal ApoBDs can be used for the diagnosis of active autoimmune hepatitis, particularly in early biopsies when no other conventional characteristics can be found [ 129 ].…”