Intraepithelial CD3+ and CD4+ Cells as Unique Surrogate Markers for Mucosal Immunity in Irritable Bowel Syndrome

Abstract

Purpose: Irritable Bowel Syndrome (IBS) is the most common functional bowel disease in the world, particularly in the western society. The estimated prevalence is 10-20%. The exact etiology is still not elucidated. It is multifactorial with various etiologies postulated including discordant communication in the brain gut axis, genetic, environmental, infectious, stress and possible intra mucosal immune disarray. Mast cell proctopathy has been described in diarrheal type of IBS (IBS-D). Tight junction dysfunction has been proposed for the constipation type of IBS (IBS-C). Intra epithelial predominance of immune cell activation has also been observed. We proposed a clinico-pathological pilot study to correlate mucosal immune activity (intraepithelial CD3+, CD4+ and mast cells) quantitatively with subsets of IBS (IBS-C and IBS-D). Methods: Sixty (N=60) patients (age range: 29 to 45) satisfying ROME III criteria for IBS were enrolled from an urban community practice with diverse ethnicity in New York City, equally divided into IBS-D (n=20), IBS-C (n=20) and twenty patients (n=20) without IBS or Inflammatory Bowel Disease(IBD) as age-matched controls. Initial Blood work and stool samples were taken to rule out any concomitant inflammatory bowel disease or other active bowel infections. All patients underwent flexible sigmoidoscopy and four quadrant proximal descending colonic biopsies. All samples were evaluated for mast cells in high power with Tryptase stain and a quantitative immuno-histochemical stain for CD3+ and CD4+ in lamina propria. (Caris Laboratories, Irving, Texas) Exclusions: Patients with HIV, IBD, Microscopic and lymphocytic colitis, Celiac disease, bacterial or parasitic gastrointestinal Infections or infestations, those on drugs altering Gut immunity (steroids, Chemotherapy, radiotherapy, Interferons, TNF Alfa antagonists, immunosuppressives etc.) Results:Tables 1 and 2.Table 1Table 2Conclusion: This study demonstrates that intra-epithelial immune activity plays a definite role in IBS population. Further statistical analysis reveals no significant difference between IBS-D and IBS-C subsets. Larger prospective studies will further establish immune activity and its role in induction of symptoms in IBS and its subsets.