Granulomas of Intestinal Tuberculosis and Crohn's Disease Can Be Differentiated by CD73 Cell Surface Marker Expression: A Pilot Study

Abstract

Intestinal tuberculosis (ITB) and Crohn's disease are similar granulomatous disorders. Granulomas are present in both and difficult to differentiate on histopathology alone. A recent study demonstrated recruitment of mesenchymal cells (MSCs) at the periphery of granulomas in lymph node tuberculosis which suppressed T cell responses. We hypothesized that granulomas of ITB would also recruit MSCs to evade host immune response. The purpose of this study was to demonstrate MSC markers in granulomas of ITB and evaluate whether distribution of MSC markers could differentiate between granulomas of Crohn's and ITB. We initially retrospectively enrolled 17 patients with confirmed ITB (8) or Crohn's (9) with granulomas on histopathology. Tissues were evaluated by immunofluorescence for MSC markers CD29, CD90, CD73 and absence of haematopoietic markers CD31, CD34, CD45 and CD14. Double-staining was done to confirm presence of MSCs. Subsequently, 23 postoperative specimens of Crohn's (18) and ITB (5) were analyzed for validation. Overall, 27 Crohn's and 13 ITB cases were assessed. CD29 and CD90 positive cells were noted around both ITB and Crohn's granulomas. MSC marker CD73 was expressed around the granulomas of ITB alone and was completely absent in the Crohn's. The subsequent assessment of granulomas in postoperative specimens of Crohn's and ITB also showed similar results. Granulomas of ITB and Crohn's disease can be differentiated by CD73 MSC surface marker expression. The differential CD73 expression around ITB granuloma indicates that Mycobacterium tuberculosis evades host immunity by recruiting MSCs with CD73 expression. MSCs with increased CD73 expression could be the future for therapeutic intervention in Crohn's.