A Refractory Celiac Patient Successfully Treated With Mesenchymal Stem Cell Infusions Rachele Ciccocioppo, MD, Alessandra Gallia, MD, Maria A. Avanzini, PhD, Elena Betti, BSc, Cristina Picone, MSc, Alessandro Vanoli, MD, Chiara Paganini, MSc, Federico Biagi, MD, Rita Maccario, PhD, Gino R. Corazza, MD Mayo Clinic Proceedings Volume 91, Issue 6, Pages 812-819 (June 2016) DOI: 10.1016/j.mayocp.2016.03.001 Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions
Figure 1 Chronological distribution of the patient's clinical course. The timing of the therapeutic interventions, ie, the diet regimen, corticosteroid therapy, and cellular treatment, together with that of the specific diagnostic procedures, is schematically represented, applying arbitrary distances among them. In detail, regarding the histologic analysis of the duodenal mucosa at the time of diagnosis of refractory celiac disease (RCD) and before mesenchymal stem cell (MSC) infusions (left-hand boxes), the presence of villous atrophy with crypt hyperplasia and heavy inflammatory infiltrate is clearly evident. After 2 MSC infusions (central boxes), a slight improvement in mucosal architecture is seen. At the end of the MSC treatment and after 6 months (right-hand boxes), the recovery of a healthy mucosa with normal architecture is observed. The histologic sections were stained with hematoxylin-eosin (original magnification, ×100). The lower boxes indicate the flow cytometric analyses of intraepithelial lymphocytes at each time point of the MSC treatment, as determined after the cells with strong CD45 expression and low side scatter were selected, and the dot plot cytoplasmic CD3 vs surface CD3, on CD7+ gate, was performed, thus showing the invariable presence of an aberrant T-cell population lacking in surface CD3 but displaying cytoplasmic CD3. AEA = antienterocyte antibody; ATA = anti–tissue transglutaminase antibody; CD = celiac disease; EMA = antiendomysial antibody. Mayo Clinic Proceedings 2016 91, 812-819DOI: (10.1016/j.mayocp.2016.03.001) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions
Figure 2 Interleukin (IL)-15/IL-15 receptor α (IL-15Rα) mucosal levels. A, Immunoblotting using the monoclonal anti–IL-15, anti–IL-15Rα, and anti–β-actin antibodies on mucosal samples from representative cases of healthy controls (HCs), patients with treated celiac disease (TCD), patients with untreated celiac disease (UCD), and the present patient with refractory celiac disease (RCD) throughout the treatment period. The protein levels of IL-15 (B) and IL-15Rα (C) were measured by scanning densitometry as band area (black bars) and band intensity (gray bars), expressed as mean ± SD arbitrary units (AUs), and normalized toward β-actin levels. Mayo Clinic Proceedings 2016 91, 812-819DOI: (10.1016/j.mayocp.2016.03.001) Copyright © 2016 Mayo Foundation for Medical Education and Research Terms and Conditions