Differences in colonic disease activity in patients with ulcerative colitis with and without primary sclerosing cholangitis

PURPOSE: A small group of patients with ulcerative colitis (UC) also suffer from primary sclerosing cholangitis (PSC). Genetic and immunologic differences exist between UC patients with and without concomitant PSC. Furthermore, UC patients with PSC are more prone to developing colonic dysplasia/aneuploidy compared with patients with UC only. Because colonic disease activity and treatment with sulfasalazine have been found to be of independent importance for development of colonic carcinoma in UC, this study aims to determine if differences exist concerning colonic disease activity in UC patients with and without PSC. METHODS: Twenty-nine PSC patients with total colitis were matched to two UC patients with total colitis but without liver disease. Case records and questionnaires were used to gain information on pharmacologic treatment and disease activity. RESULTS: Observation time was 20 (PSC group) and 23 years (UC only). Number of patients taking prophylactic treatment did not differ between groups. Patients with UC only had received treatment with systemic and local corticosteroids significantly more often than UC patients with PSC (P < 0.05 and P < 0.02). Patients with UC only were hospitalized because of colonic activity significantly more often (P < 0.02). Number of patients undergoing colectomy because of disease activity or number of patients with chronic continuous symptoms did not differ between the two groups. CONCLUSION: UC in patients with PSC runs a milder course than UC in patients without this complication, although the number of patients taking prophylactic treatment was the same. If lower disease activity reflects differences in pathogenesis of UC in patients with PSC or if it can explain increased risk to develop colonic malignancy in patients with both PSC and UC needs further elucidation.Supported by grants from Nanna Svartz Scholarship, Stockholm, Sweden.     

Fas/Fas Ligand Expression and Characteristics of Primed CD45RO+ T Cells in the Inflamed Mucosa of Ulcerative Colitis

Background: Chronic immune activation in the colon is characteristic of ulcerative colitis (UC). Fas/Fas ligand (FasL) system is a mechanism responsible for activation-induced cell death (AICD), which maintains homeostasis within the immune system. Thus, Fas/FasL expression on activated colonic T cells of UC patients, as well as the susceptibility of such T cells to AICD was investigated in order to determine the role of activated colonic T cells in the long lasting inflammation in UC. Methods: Fas, FasL, and CD45RO expression on peripheral blood and colonic T cells of UC patients were assayed by flow cytometry. Apoptosis of colonic T cells induced by anti Fas antibody was assessed using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Results: The majority of colonic T cells expressed both CD45RO and Fas in the colonic mucosa, a situation that was quite different from that in the peripheral blood. The number of CD45RO⁺CD8⁺ and Fas⁺CD8⁺ T cells was significantly lower in UC patients than the controls, unlike the number of Fas⁺CD4⁺ T cells. In contrast, the number of both CD45RO⁺CD4⁺ and CD45RO⁺CD8⁺ T cells in UC mucosa expressing FasL was significantly higher than in the controls. While Fas mediated apoptosis of CD45RO⁺CD8⁺ T cells was higher in UC patients than the controls, the number of apoptotic CD45RO⁺CD4⁺ T cells from UC mucosa was not. Conclusions: In UC patients, CD45RO⁺CD4⁺ T cells are less sensitive to apoptotic signals mediated by Fas. These phenomena may contribute to the pathogenesis of UC.     

Interstitial cells of cajal and inflammation-induced motor dysfunction in the mouse small intestine

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) play an important role in the control of gastrointestinal motility. We aimed to determine a potential role for ICC in the pathophysiology of inflammation-induced motor disorders. METHODS: Effects of Trichinella spiralis infection on electrical pacemaker activity, the structure of ICC associated with Auerbach's plexus, and in vivo motor patterns were studied in the mouse small intestine. RESULTS: Between days 1 and 15 after infection, structural damage occurred in the network of ICC, particularly in the processes connecting ICC to each other and to smooth muscle cells. This was associated with desynchronization of electrical pacemaker activity. Abnormal slow wave activity occurred, including doubling of frequency and electrical quiescence, leading to the development of ectopic pacemaker activity in vivo. In vivo motor patterns in the small intestine changed from consistent peristaltic contractile activity in control animals to periods of quiescence alternating with both orally and aborally propagating contractile activity in the presence of inflammation. Sixty days after infection, all parameters studied had returned to normal values. CONCLUSIONS: Inflammation-induced alterations in the network of ICC of the small intestine associated with Auerbach's plexus lead to disorganization of motor patterns. Because of the strong temporal correlation between damage to the ICC network, electrical uncoupling, the appearance of ectopic pacemaker activity, and the occurrence of retrograde peristalsis, it is concluded that ICC can play a major role in inflammation-induced motor disturbances.     

Decreased interstitial cells of Cajal in the sigmoid colon of patients with slow transit constipation

Background and aims Slow transit constipation (STC) is a colonic motor disorder that is characterized by measurably delayed movement of materials through the colon. Although abnormalities in the neuronal networks of the colon have been demonstrated in patients with STC, the etiology of STC remains unclear. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the intestine and have been implied in the pathogenesis of a number of gastrointestinal motility dysfunctions, including idiopathic STC. This study aimed to determine the normal distribution of ICC within the colon of the Chinese and also to determine if ICC are decreased in Chinese STC patients.Patients and methods Twelve patients with STC and eight age-matched normal controls were studied. Specimens of sigmoid colon were obtained immediately after resection. ICC were identified with a monoclonal antibody to c-kit by an indirect immunofluorescence method. Immunostained tissues were examined with a laser scanning confocal microscope and the area occupied by ICC was calculated with an image analysis system.Results ICC were located in the external muscle layers including myenteric plexus (MP) and submucosal border (SMB). Two types of Kit-positive ICC were observed: bipolar cells characterized by one or two long processes and multipolar cells characterized by long stellate processes extending in various directions. A higher percentage of ICC was present in the MP regions and circular muscle (CM) layers compared with the SMB and longitudinal muscle (LM) layers. Tissues from STC patients showed a considerable decrease in the number of ICC located in the four regions (ICC-LM, ICC-MP, ICC-CM, ICC-SMB), especially the ICC-SMB, in which ICC almost completely disappeared.Conclusions Similar distribution of ICC was observed in the normal sigmoid colon of the Chinese. Decreased area of c-kit+ ICC may play an important role in the pathophysiology of STC. It remains to be determined whether the loss of ICC is primary or secondary to another lesion.     

Spontaneous electrical activity of interstitial cells of Cajal isolated from canine proximal colon.

Interstitial cells of Cajal (ICC) have been suggested as pacemaker cells in the gastrointestinal tract. A method was developed to isolate ICC from the slow-wave pacemaker region of the canine proximal colon. These cells were identified under phase-contrast microscopy, and their identity was verified by comparing their ultrastructure with the morphology of ICC in situ. Patch-clamp experiments demonstrated that these cells are excitable; voltage-dependent inward and outward currents were elicited by depolarization. Inward current transients were identified as calcium currents. A portion of the outward current appears to be due to Ca2+-activated K channels commonly expressed in these cells. ICC were also spontaneously active, generating electrical depolarizations similar in waveform to slow-wave events of intact colonic muscles. These findings are consistent with the hypothesis that ICC initiate rhythmicity in the colon.     

Sialyl-Tn antigen as a marker of colon cancer risk in ulcerative colitis: Relation to dysplasia and DNA aneuploidy

Background & Aims: Expression of the mucin-associated carbohydrate antigen sialyl-Tn (STn) and DNA aneuploidy has each been shown to correlate with malignant transformation in patients with sporadic colon cancer and in those with ulcerative colitis (UC). This study aimed to determine how STn expression topographically and temporally relates to aneuploidy and neoplasia in patients with long-standing UC. Methods: Twenty-six patients enrolled in a cancer surveillance program were studied, and 1691 mucosal specimens from repeated colonoscopies and colectomies were assessed in a standardized, prospective fashion for the presence of dysplasia, aneuploidy, and STn antigen. Results: STn was expressed in 47% of specimens from 6 patients who underwent colectomy for dysplasia and 7% of specimens from 6 well-matched patients who underwent surgery for medical intractability. Seven other patients who never developed dysplasia or aneuploidy expressed STn in 6% of biopsy specimens. STn expression was independent of aneuploidy in colons both with and without dysplasia. Of 5 patients with aneuploidy but without dysplasia, 4 expressed STn earlier than aneuploidy. Conclusions: In UC, STn antigen and DNA aneuploidy are independent markers of neoplastic transformation. Determination of STn expression may complement dysplasia and aneuploidy for identification of risk for colonic neoplasia in UC.GASTROENTEROLOGY 1998;115:1395-1404     

参青方对TNBS诱导的大鼠结肠炎模型结肠Cajal间质细胞的影响

背景：近年以Cajal间质细胞（ICC）为核心的肠道动力学与溃疡性结肠炎（UC）的关系逐渐成为UC研究的热点之一。目的：观察中药制剂参青方对三硝基苯磺酸（TNBS）诱导的大鼠结肠炎模型结肠组织中ICC形态和数量的影响，探讨该制剂调节UC肠道动力障碍的作用机制。方法：60只大鼠随机分为正常对照组、模型Ⅰ组、模型Ⅱ组、美沙拉秦组、参青方高剂量组和低剂量组，后5组以TNBS诱导结肠炎模型。模型Ⅰ组于造模后3d取材，其余5组于造模后3d开始予相应药物，连续给药7d后取材。电子显微镜观察病变结肠组织ICC超微结构，免疫组化染色和蛋白质印迹法检测c-kit蛋白表达。结果：模型Ⅰ组结肠组织ICC超微结构破坏明显，c-kit蛋白表达较正常对照组显著降低（P〈0．05）。经参青方或美沙拉秦治疗后，ICC超微结构异常有所改善，c-kit蛋白表达显著增高（P〈0．05），参青方高剂量组作用更为明显。结论：TNBS诱导的结肠炎大鼠结肠组织ICC超微结构损伤，数量减少，而参青方能减轻和修复ICC损伤并恢复其数量，对调节肠道动力起重要作用。     

Pan-colonic decrease in interstitial cells of Cajal in patients with slow transit constipation

BACKGROUND: Interstitial cells of Cajal (ICC) are required for normal intestinal motility. ICC are found throughout the human colon and are decreased in the sigmoid colon of patients with slow transit constipation. AIMS: The aims of this study were to determine the normal distribution of ICC within the human colon and to determine if ICC are decreased throughout the colon in slow transit constipation. PATIENTS: The caecum, ascending, transverse, and sigmoid colons from six patients with slow transit constipation and colonic tissue from patients with resected colon cancer were used for this study. METHODS: ICC cells were identified with a polyclonal antibody to c-Kit, serial 0.5 microm sections were obtained by confocal microscopy, and three dimensional software was employed to reconstruct the entire thickness of the colonic muscularis propria and submucosa. RESULTS: ICC were located within both the longitudinal and circular muscle layers. Two networks of ICC were identified, one in the myenteric plexus region and another, less defined network, in the submucosal border. Caecum, ascending colon, transverse colon, and sigmoid colon displayed similar ICC volumes. ICC volume was significantly lower in the slow transit constipation patients across all colonic regions. CONCLUSIONS: The data suggest that ICC distribution is relatively uniform throughout the human colon and that decreased ICC volume is pan-colonic in idiopathic slow transit constipation.     

Interstitial cells of Cajal are present in human extrahepatic bile ducts

Background and Aims: Interstitial cells of Cajal (ICC) are distributed with smooth muscle throughout the gastrointestinal tract and are involved in regulating motility. ICC were recently discovered in the wall of the human gallbladder. This study sought to determine whether ICC are present in human bile ducts. Methods: Biliary tract samples were obtained from several sources: surgical specimens (n = 16, 11 women, mean age 61 years); archival post‐mortem specimen (n = 1, 86 years, man); and cadavers (n = 2, 68 and 80 years, men). Paraffin‐embedded sections (3 µm) from the gallbladder (fundus, body and neck) and both extrahepatic and intrahepatic bile ducts were investigated. A double immunofluorescence protocol using polyclonal and monoclonal c‐kit antibodies and mast cell tryptase was used to distinguish c‐kit‐positive cells with typical ICC morphology from c‐kit‐positive mast cells. Small bowel samples were used as positive controls. ICC in the gallbladder were confirmed by ultrastructural study. Results: c‐kit‐positive cells with characteristic ICC morphology were identified in the subepithelial and muscular layers of the gallbladder and extrahepatic bile ducts. They were most prominent within the muscle layer of the extrahepatic bile ducts where they were organized into loosely arranged laminae running parallel to circular smooth muscle fibers. ICC were not found in intrahepatic bile ducts. Conclusion: This study demonstrates for the first time that ICC are present in human extrahepatic bile ducts where they are more densely aggregated than in the gallbladder. This cellular network is likely to be involved in biliary tract motility and its related disorders.     

Septal interstitial cells of Cajal conduct pacemaker activity to excite muscle bundles in human jejunum

BACKGROUND & AIMS: Like the heart, intestinal smooth muscles exhibit electrical rhythmicity, which originates in pacemaker cells surrounding the myenteric plexus, called interstitial cells of Cajal (ICC-MY). In large mammals, ICC also line septa (ICC-SEP) between circular muscle (CM) bundles, suggesting they might be necessary for activating muscle bundles. It is important to determine their functional significance, because a loss of ICC in humans is associated with disordered motility. Our aims were therefore to determine the role of ICC-SEP in activating the thick CM in the human jejunum. METHODS: The mucosa and submucosa were removed and muscle strips were cut and pinned in cross-section so that the ICC-MY and ICC-SEP networks and the CM could be readily visualized. The ICC networks and CM were loaded with the Ca(2+) indicator fluo-4, and pacemaker and muscle activity was recorded at 36.5 +/- 0.5( degrees )C. RESULTS: Ca(2+) imaging revealed that pacemaker activity in human ICC-MY can entrain ICC-SEP to excite CM bundles. Unlike the heart, pacemaker activity in ICC-MY varied in amplitude, propagation distance, and direction, leading to a sporadic activation of ICC-SEP. CONCLUSIONS: ICC-SEP form a crucial conduction pathway for spreading excitation deep into muscle bundles of the human jejunum, necessary for motor patterns underlying mixing. A loss of these cells could severely affect motor activity.     

Collagenase-3 (MMP-13) expression by inflamed mucosa in inflammatory bowel disease

Objective. To determine whether the expression of collagenase-3 (MMP-13) in biopsies from patients with inflammatory bowel disease is correlated with histological inflammation parameters. Material and methods. Fifty-nine patients with inflammatory bowel disease were included in the study. The control group comprised 20 patients free of inflammatory disease and ten patients with acute diverticulitis. MMP-13 expression was determined by immunohistochemical staining and the specimens were assigned a histological inflammation score. Results. It was found that 62.8% of patients with ulcerative colitis (UC) and 54.1% of patients with Crohn's disease (CD) showed MMP-13-positive immunostaining in biopsies from affected areas. MMP-13-positive staining was more intense in ulcerated colonic mucosa. A positive and significant correlation was found between MMP-13 expression and the histological inflammation scores in mucosal samples from patients with CD (r=0.74, p<0.0001) or UC (r=0.62, p<0.0001). However, no MMP-13-positive immunostaining was found in either the biopsy specimens of the control group or those biopsies taken from patients with UC or CD in microscopically confirmed non-affected areas of the colonic mucosa. Similarly, colonic mucosa samples of the 10 patients with acute diverticulitis did not show immunostaining for MMP-13. Conclusions. Our findings demonstrating the absence of MMP-13 expression in non-inflamed colonic mucosa or in acute diverticulitis, as well as a positive correlation between elevated MMP-13 expression and histological criteria of inflammation in patients with inflammatory bowel diseases (CD and UC) suggest a role of the protease in the pathogenesis of these latter processes.     

The mechanism and spread of pacemaker activity through myenteric interstitial cells of Cajal in human small intestine

BACKGROUND & AIMS: It has been generally assumed that interstitial cells of Cajal (ICC) in the human gastrointestinal tract have similar functions to those in rodents, but no direct experimental evidence exists to date for this assumption. This is an important question because pathologists have noted decreased numbers of ICC in patients with a variety of motility disorders, and some have speculated that loss of ICC could be responsible for motor dysfunction. Our aims were to determine whether myenteric ICC (ICC-MY) in human jejunum are pacemaker cells and whether these cells actively propagate pacemaker activity. METHODS: The mucosa and submucosa were removed, and strips of longitudinal muscle were peeled away to reveal the ICC-MY network. ICC networks were loaded with the Ca(2+) indicator fluo-4, and pacemaker activity was recorded via high-speed video imaging at 36.5 degrees C +/- 0.5 degrees C. RESULTS: Rhythmic, biphasic Ca(2+) transients (6.03 +/- 0.33 cycles/min) occurred in Kit-positive ICC-MY. These consisted of a rapidly propagating upstroke phase that initiated a sustained plateau phase, which was associated with Ca(2+) spikes in neighboring smooth muscle. Pacemaker activity was dependent on inositol 1,4,5-triphosphate receptor-operated stores and mitochondrial function. The upstroke phase of Ca(2+) transients in ICC-MY appeared to result from Ca(2+) influx through dihydropyridine-resistant Ca(2+) channels, whereas the plateau phase was attributed to Ca(2+) release from inositol 1,4,5-triphosphate receptor-operated Ca(2+) stores. CONCLUSIONS: Each ICC-MY in human jejunum generates spontaneous pacemaker activity that actively propagates through the ICC network. Loss of these cells could severely disrupt the normal function of the human small intestine.     

Abnormal distribution of the interstitial cells of cajal in an adult patient with pseudo-obstruction and megaduodenum

Interstitial cells of Cajal (ICC) are fundamental regulators of GI motility. Here, we report the manometrical abnormalities and abnormalities of ICC distribution and ultrastructure encountered in a 30-yr-old patient with megaduodenum and pseudo-obstruction. Full thickness biopsies taken during laparoscopic placement of a jejunostomy showed vacuolated myocytes and fibrosis predominantly in the outer third of the circular muscle layer of the duodenum, suggestive for visceral myopathy. The distribution of ICC was also strikingly abnormal: by light microscopy, ICC surrounding the myenteric plexus were lacking in the megaduodenum, whereas ICC were normally present in the duodenal circular muscle and in the jejunum. By electron microscopy, very few ICC were identified around the duodenal myenteric plexus. These findings suggest that abnormalities in ICC may contribute to the disturbed motility in some myopathic forms of intestinal pseudo-obstruction.     

The association between antigenemia,histology with immunohistochemistry,and mucosal PCR in the diagnosis of ulcerative colitis with concomitant human cytomegalovirus infection

Background

Human cytomegalovirus (HCMV) colitis can be involved in active ulcerative colitis (UC) in patients refractory to steroid and immunosuppressive drugs. Histological examination with colonic biopsy specimens and antigenemia assays are the standard tests for diagnosing HCMV enterocolitis, and we have previously reported the usefulness of mucosal polymerase chain reaction (PCR) methods. However, the associations among histopathological tests, antigenemia assays, and mucosal PCR are unknown.

Methods

We retrospectively analyzed 82 UC patients who underwent mucosal biopsy from inflamed colonic tissues for histological evaluation and mucosal PCR to detect HCMV. We analyzed the relationships between the HCMV-DNA copy number in colonic mucosa and other HCMV tests.

Results

In total, 131 HCMV mucosal PCR tests from 82 UC patients were positive. The HCMV-DNA copy number was significantly higher in patients with positive immunohistochemistry (IHC) (p < 0.01) and was correlated with the number of positive cells for the antigenemia (C7-HRP, p < 0.01; C10/11, p < 0.01). Receiver operating characteristic curve analysis confirmed 1300 copies/μg of HCMV-DNA as the best diagnostic cut-off value to predict positive results of antigenemia (area under the curve = 0.80, 95% CI 0.68–0.93). HCMV-DNA copy number also correlated with the total UCEIS score (p = 0.013) and the bleeding score (p = 0.014). For each individual patient, a positive correlation between the change in total UCEIS score and HCMV-DNA copy number was observed (p = 0.040).

Conclusion

The antigenemia assay and histopathological test with IHC were significantly associated with the HCMV-DNA copy number in colonic tissues. Moreover, endoscopic examination with the UCEIS can help diagnose the HCMV colitis in UC patients.

     

Peptidergic nerves in the colon of patients with ulcerative colitis

BACKGROUND/AIMS: The cause of impaired motility, such as diarrhea and toxic megacolon, in patients with ulcerative colitis is unknown. Neuropeptides have recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic inhibitory and excitatory nerves in the human gut. To clarify the physiological significance of vasoactive intestinal polypeptide, substance P and neurotensin in the colon of patients with ulcerative colitis, we investigated the enteric nerve responses on lesional and normal bowel segments derived from patients with ulcerative colitis and patients who underwent colon resection for colonic cancers. METHODOLOGY: Twenty-four specimens were obtained from the lesional colon of 6 patients with ulcerative colitis (4 male, 2 female; ages 14-51 years, mean: 40.3 years). The patients with ulcerative colitis had chronic disease (4 with moderate disease, 2 with severe disease). Seventy-two specimens were obtained from the normal colon of 10 patients with colonic cancer (8 men and 2 women; ages 40-56 years, mean: 51.2 years). A mechanographic technique was used to evaluate in vitro muscle responses to these peptides of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. RESULTS: (1) Peptidergic nerves such as vasoactive intestinal polypeptide, substance P, and neurotensin nerves were found to act on both normal colon and ulcerative colitis colon; (2) the colon with ulcerative colitis was more strongly innervated by vasoactive intestinal polypeptide nerves than the normal colon; (3) Substance P and neurotensin nerves act more weakly in the UC colon that the normal colon. CONCLUSIONS: These findings suggest that peptidergic nerves play an important role in the impaired motility observed in patients with UC.     

Role of non-adrenergic non-cholinergic inhibitory nerves in the colon of patients with ulcerative colitis

The cause of impaired colonic motility in patients with ulcerative colitis (UC) is unknown. The non-adrenergic non-cholinergic (NANC) inhibitory nervous system is one of the most important factors in the enteric nervous system of human gut. To assess the physiological significance of NANC inhibitory nerves in the colon of patients with UC, we investigated the enteric nerve responses of colonic tissues from patients with this disease. Colonic tissues were obtained from the lesional sigmoid colons of six patients with UC. Normal sigmoid colonic tissues obtained from ten patients with colonic cancer were used as controls. A mechanographic technique was used to evaluate in-vitro muscle responses to the electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. NANC inhibitory nerves were found to act on both normal colon and the lesional colon of patients with UC, but colon with UC was more strongly innervated by NANC inhibitory nerves than was the normal colon. These findings suggest that NANC inhibitory nerves play an important role in the impaired motility observed in the colon of patients with UC. Received Feb. 3, 1997; accepted May 23, 1997     

Detection of cytomegalovirus by immunohistochemistry of colonic biopsies and quantitative blood polymerase chain reaction: evaluation of agreement in ulcerative colitis

Objectives: Cytomegalovirus (CMV) often reactivates in ulcerative colitis (UC). In diagnostics, along with immunohistochemistry (IHC) of colonic biopsies, blood CMV polymerase chain reaction (PCR) is gaining increasing application. We aimed to assess agreement between the density of infected colonic cells by IHC and the viral load in the blood by PCR.

Material and methods: We retrospectively identified patients with active UC or indeterminate colitis in whom blood CMV PCR had been performed while biopsies had been taken simultaneously. The latter were re-evaluated and the numbers of IHC–positive cells per square millimetre counted.

Results: The analyses extended to 234 sample pairs, among which there were 184 cases (78.6% of the total) in which IHC was equal to 0. The median among the remaining 50 non-zero values for IHC was 1.7 cells/mm². PCR was equal to 0 in 192 cases (82.1%), while the median among the remaining 42 non-zero values was 4995.3?IU/ml. The Spearman correlation coefficient was 0.43 (p?5.6 cells/mm²), where PCR?>?0 had a sensitivity of 0.615 and a specificity of 0.846.

Conclusions: In active CMV colitis, the specificity and negative predictive value of blood PCR are high, while the sensitivity grows with the intensity of colon infection. A highly positive result could justify the administration of antiviral treatment being brought forward in selected patients.     

Changes in Distribution of Three Isoforms of Nitric Oxide Synthase in Ulcerative Colitis

Background: Nitric oxide (NO) has an important role both in normal physiology and pathological events of the colon. Our aim was to study possible changes of the three nitric oxide synthases in ulcerative colitis (UC). Methods: Tissue samples from normal colon and least and moderately affected regions of ulcerative colitis colon were obtained at surgery and immunostained for NOS-1, NOS-2, NOS-3, and GAP-43, a marker of nerve fibers. Quantitative analysis of NOS-1 immunoreactivity was performed on the circular muscle layer. Results: NOS-1-immunoreactive fibers in the muscularis mucosae disappeared in least affected and moderately affected UC colon. Quantitative analysis of NOS-1-immunoreactive nerve fibers in the circular muscle showed no differences between normal and diseased colon. NOS-2 immunoreactivity appeared apically in the epithelial cells. In normal colon some specimens showed immunoreactivity in lower parts of crypts. NOS-2 immunoreactivity increased according to the severity of UC. NOS-3 immunoreactivity was exclusively localized in the vascular endothelium. The difference in NOS-3 staining intensity between the lamina propria and submucosa observed in normal tissue disappeared in moderately affected UC colon. The number of NOS-3-immunoreactive vascular profiles increased in the lamina propria of UC colon. Conclusions: All three NOS isoforms show specific changes in UC colon.     

Ulcerative Colitis and Immunoglobulin G4

Background/Aims

Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4.

Methods

Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients.

Results

UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05).

Conclusions

UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.