Mesenchymal Stromal Cell Infusions as Rescue Therapy for Corticosteroid-Refractory Adult Autoimmune Enteropathy

Abstract

Adult autoimmune enteropathy (AIE) is a rare cause of malabsorption syndrome unresponsive to dietary restriction. Its diagnostic hallmarks are small-bowel villous atrophy and antienterocyte autoantibodies. Therapy is based mainly on nutritional support and immunosuppression. We treated a 61-year-old woman with corticosteroid-refractory AIE and life-threatening malabsorption syndrome with systemic infusions of autologous, bone marrow-derived, mesenchymal stromal cells (MSCs) as rescue therapy. The MSCs were expanded ex vivo following a previously used Good Manufacturing Practice procedure, and 2 intravenous infusions of 1.8 ϫ 10 6 MSCs/kg body weight were administered 2 weeks apart. Analysis of circulating and mucosal regulatory T-and B-cell numbers, and of serum and secretory immunoglobulin levels, was performed before and after treatment. The MSC infusions were safe and effective, leading to disappearance of disease hallmarks and recovery from the life-threatening condition. Increases in mucosal regulatory T-cell numbers and secretory immunoglobulin levels were also observed. The benefit, however, was transient, and a further MSC infusion resulted in the same short efficacy. This case encourages the use of MSCs to treat patients with lifethreatening, corticosteroid-refractory AIE and suggests that MSC infusion can attenuate, albeit transiently, the autoimmune attack.

Immunoregulatory properties of clinical grade mesenchymal stromal cells: evidence, uncertainties, and clinical application

“…Quantification of IDO activity in plasma should also be evaluated in this context [47]. As previously described in cancer immunotherapy, collection of biopsies after local MSC administration could be highly informative to better understand both their direct and indirect immune activity [4,48]. …”

Is a detailed grading of villous atrophy necessary for the diagnosis of enteropathy?

“…They should focus on judging biopsy orientation and whether the biopsy is atrophic or not. A histological grading does not add anything to the final diagnosis and it does not correlate with clinical features or prognosis 8 15 20 21…”

Concise Review: Cellular Therapies: The Potential to Regenerate and Restore Tolerance in Immune-Mediated Intestinal Diseases

“…In this regard, a remarkable ability to inhibit both proliferation of gliadin‐specific T cells and production of pro‐inflammatory cytokines has recently been shown , thus providing the experimental background for prompt clinical use. To date, the only case that underwent intravenous infusions of autologous bone marrow‐derived MSC was an adult female suffering from severe malabsorption syndrome due to autoimmune enteropathy . The latter is an immune‐mediated condition whose intestinal lesions resemble those of celiac disease, but it is unresponsive to any dietary restriction and displays the anti‐enterocyte autoantibodies as a diagnostic hallmark .…”