Appendix is a priming site in the development of ulcerative colitis

Abstract

AIM:The role of the appendix has been highlighted in the pathogenesis of ulcerative colitis (UC). The aims of this study were to elucidate the immuno-imbalances in the appendix of UC patients, and to clarify the role of the appendix in the development of UC. METHODS:Colonoscopic biopsy specimens of the appendix, transverse colon, and rectum were obtained from 86 patients with UC: active pancolitis (A-Pan; n = 15), active left-sided colitis (A-Lt; n = 25), A-Lt with appendiceal involvement (A-Lt/Ap; n = 10), inactive pancolitis (I-Pan; n = 14), and inactive left-sided colitis (I-Lt; n = 22), and from controls. In the isolated mucosal T cells, the CD4/CD8 ratio and proportion of activated CD4+ T cells were investigated, and compared with controls. RESULTS:In the appendix, the CD4/CD8 ratio significantly increased in A-Lt and A-Lt/Ap. The ratio in the appendix also tended to increase in A-Pan. In the rectum, the ratio significantly increased in all UC groups. In the appendix, the proportion of CD4+CD69+ (early activation antigen) T cells significantly increased in all UC groups. In the rectum, the proportion of CD4+CD69+ T cells significantly increased only in A-Pan. The proportion of CD4+HLA-DR+ (mature activation antigen) T cells significantly increased only in the rectum of A-Pan, but not in the other areas of any groups. CONCLUSION:The increased CD4/CD8 ratio and predominant infiltration of CD4+CD69+ T cells in the appendix suggest that the appendix is a priming site in the development of UC.

Appendiceal Orifice Inflammation in an 8-Year-Old Girl with Ulcerative Colitis Complicating Wilson's Disease

“…Matsushita and coworkers studied immune-imbalances in the appendices of UC patients and reported that the appendix is a priming site for UC development, showing an enhanced CD4/CD8 cell ratio, and a prominent population of CD4＋CD69＋ T cells. 6 Yamagishi and colleagues explored the relationship between the continuous distal lesion of UC and the skipped periappendiceal lesion by observing colonoscopic changes in both lesions and reported that activity in the distal lesion correlated well with that in the skipped periappendiceal lesion. 7 Matsumoto and co-workers used colonoscopy to study two UC groups with or without AOI.…”

Diagnostic evaluation of appendiceal orifice inflammation in ulcerative colitis

“…Compared with acute appendicitis, ulcerative colitis appendices are more likely to have crypt abscesses, gland branching and shortening, and Paneth cell metaplasia and less likely to show muscularis propria infiltration by neutrophils (2). In some reports (3)(4)(5), endoscopists have identified AOI macroscopically based on the presence of mucosal erythema, congestion/erosion/ ulceration, and friability (Figure 1-3). Moreover, some other investigators have indicated that AOI may be involved in the development or pathogenesis of UC (4,6,7).…”

Peri-Appendiceal Red Patch and Pathogenesis of the Appendix in Ulcerative Colitis

“…We have disclosed that the proportion of CD4? early-but-not-mature-activated T cells is significantly increased in the appendix of UC patients [4,7], and suspect that the appendix may be a priming site in the occurrence of UC. We therefore believe that the appendix should no longer be considered an evolutionary redundancy, especially in UC patients with PARP.…”

“…Although UC is characterized by continuous and diffuse inflammation extending proximally from the rectum, PARP has been increasingly recognized in 48-86% patients with distal UC [2][3][4], as in the study of Rubin and Rothe [1]. Patients with PARP experience a more aggressive and relapsing disease courses compared with patients without PARP [3].…”

“…The pathogenesis of UC has not been determined, but an abnormal mucosal immune response plays a major role in the occurrence and pathophysiology of UC [2,4]. Extensive infiltration of lymphocytes, especially CD4?…”