A stool test in patients with active ulcerative colitis helps exclude cytomegalovirus disease

Abstract

Objectives: In severe ulcerative colitis (UC) bowel biopsy is recommended to detect the cytomegalovirus (CMV) infection capable of complicating the course of the disease. Histopathology with immunohistochemistry (IHC) is time-consuming, and a blood polymerase chain reaction (PCR) for CMV DNA is used as an alternative, notwithstanding nothing more than a moderate correlation between the two. We aimed to detect CMV DNA in the stools of patients with active UC, and to compare the results with CMV IHC in bowel biopsies.

Materials and methods: Measurement of CMV DNA in stools (copies/ml) entailed PCR, while biopsies assessed inflammation activity (Geboes scale), as well as counts of numbers of CMV IHC-positive cells/biopsy. The severity of UC was assessed using the Mayo score, stool calprotectin and concentrations of C-reactive protein in the blood.

Results: 89 of the above pairs of tests for CMV were performed among 75 patients. CMV was detected in 36/89 stool specimens and 19/89 bowel biopsies. The sensitivity of the stool-CMV PCR was thus 84.7%, while specificity was of 71.4%. The negative predictive value was 94.3% and the positive predictive value 44.4%. No difference in the severity of UC was noted between the stool CMV DNA positive and negative groups. Similarly, there was no difference in the severity of UC between the CMV IHC positive and negative groups, except for the Geboes score, more often found to be higher in CMV IHC-positive patients (p?=?.002).

Conclusions: CMV DNA was detected in the stools of 40.4% of patients with active UC. A negative test result may help to exclude bowel CMV disease.     

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.

     

Targeting cytomegalovirus during ulcerative colitis flare-ups

Introduction: Human cytomegalovirus (CMV) is a common cause of opportunistic infection leading to severe and fatal disease in immune-compromised individuals. In inflammatory bowel disease patients, particularly those with ulcerative colitis (UC), CMV is often reactivated because these patients are frequently treated with immunosuppressive agents. Many reports have described the relationship between CMV reactivation and UC exacerbation, however, a therapeutic strategy for CMV infection in UC patients has not been established.

Area covered: This review highlights therapeutic strategies for UC patients with CMV infection. Recent findings have suggested a benefit from antiviral therapy in patients with histologically proven CMV colitis and/or a high colonic CMV load as determined by quantitative PCR.

Expert commentary: To decide who requires antiviral therapies and when we start antiviral therapies, prospective studies of large numbers of UC patients with CMV infection are needed. However, we should know that the bottom-line therapy for UC patients with CMV infection is to optimally control mucosal inflammation.     

Clinical utility of cytomegalovirus antigenemia assay and blood cytomegalovirus DNA PCR for cytomegaloviral colitis patients with moderate to severe ulcerative colitis

Background and aimsClinical usefulness of cytomegalovirus (CMV) antigenemia assay and blood CMV polymerase chain reaction (PCR) in patients with ulcerative colitis (UC) needs to be evaluated.MethodsMedical records of moderate to severe UC patients between January 2001 and December 2012 were reviewed retrospectively. Diagnostic performances of CMV antigenemia assay and blood PCR to predict CMV colitis, and clinical outcome according to the results were analyzed. CMV colitis was diagnosed by H&E staining and/or CMV immunohistochemistry.ResultsOf the 229 study subjects, 83 patients (36.2%) had CMV colitis. The sensitivity and specificity of CMV antigenemia assay were 47.0% and 81.7%, and those of blood CMV DNA PCR were 44.3% and 87.9%, respectively. If either CMV antigenemia or PCR was positive in the presence of significant ulcers, the sensitivity and specificity of having CMV colitis were 67.3% and 75.7%, respectively, with the area under the receiver operating characteristic curve value of 0.717. Among patients with significant ulcers, positive CMV antigenemia (33/50 [66.0%] vs. 31/102 [30.4%]; p < 0.001) and positive blood CMV PCR (25/37 [67.6%] vs. 24/86 [27.9%]; p < 0.001) showed significantly higher probability of CMV colitis than blood test-negative patients. UC-CMV colitis patients with positive CMV antigenemia showed significantly higher rate of colectomy than those with negative antigenemia (13/39 [33.3%] vs. 5/44 [11.4%]; p = 0.015).ConclusionsAlthough CMV antigenemia and blood CMV PCR showed low sensitivity for diagnosing CMV colitis, the specificity values were high. Among UC-CMV colitis patients, CMV antigenemia showed significant association with subsequent colectomy.     

True cytomegalovirus colitis is a poor prognostic indicator in patients with ulcerative colitis flares: the 10-year experience of an academic referral inflammatory bowel disease center

Abstract

Background and aims: The impact of cytomegalovirus (CMV) colitis on long-term outcomes of ulcerative colitis (UC) flares remains controversial.

Methods: A total of 257 UC patients with moderate-to-severe flares were observed for a mean follow-up of 41.2 months. CMV colitis was defined as histopathologic confirmation of CMV inclusions obtained from macroscopic endoscopic lesions in patients with UC flares. An independent gastrointestinal pathologist prospectively reviewed all specimens. A poor outcome was defined as any of hospitalization, colectomy or death during the follow-up period.

Results: The prevalence of CMV colitis was 14% (36/257) over the 10-year study period (2007–2016). When compared to the controls, patients with CMV colitis were characterized by older age, higher disease activity, endoscopic deep ulcerations and more frequent use of immunosuppressive drugs (all p?p?Conclusions: True CMV colitis is a poor prognostic indicator among patients with UC flares. An effective strategy for managing recurrent CMV colitis is urgently needed (KCT0003296).     

Investigation of Cytomegalovirus in Intestinal Tissue in a Country With High CMV Seroprevalence

Background: In Turkey, cytomegalovirus (CMV) seropositivity has been reported to be high, between 85 and 100%. CMV has been responsible for disease exacerbation in inflammatory bowel disease (IBD). We aimed to evaluate the presence of CMV in intestinal tissue by immunohistochemical staining in IBD and non-IBD patient groups, in a country with high CMV seroprevalence.Methods: In this prospective cross-sectional study, the presence of intestinal CMV was investigated with tissue immunohistochemistry (IHC) staining, which is accepted as the gold standard method, and with polymerase chain reaction (PCR) in tissue and blood. Patients (≥18 years old, n = 189) who had a colonoscopic biopsy between January and May 2017 were included in the study at our hospital. Clinical, laboratory, endoscopic, and histopathological data of patients were assessed by dividing them into IBD (n = 34) and non-IBD (n = 155) groups.Results: In this study, 567 colonic biopsy samples from 189 patients were evaluated. Tissue IHC staining was positive for 3 (1.58%) non-IBD patients. One of them was diagnosed as CMV ileitis. CMV DNA was also detected in 14 plasma (7.40%, <80-469 copies/mL) and 20 tissue samples (10.69%, 7-15 289 copies/mL). Tissue IHC staining is accepted as the gold standard for CMV ileitis, and the sensitivity and specificity of tissue PCR was 33% and 89.67%, while the sensitivity and specificity of plasma PCR was 66.66% and 93.54%, respectively.Conclusion: Although CMV seroprevalence is high in Turkey, CMV ileitis was diagnosed in only one non-IBD patient (0.53%). Compared to tissue IHC staining, the sensitivity of tissue and blood CMV PCR was low while their specificity was higher.     

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.     

Cytomegalovirus in pediatric inflammatory bowel disease patients with acute severe colitis

BackgroundThe prevalence and significance of cytomegalovirus (CMV) colitis in pediatric acute severe colitis is unknown. The aim of this study was to determine the prevalence of CMV in colonic mucosa of children with acute severe refractory colitis and compare the clinical characteristics and outcomes of CMV positive and negative patients.MethodsIn a case-control study, colonic biopsy specimens from children with severe refractory colitis were tested for CMV, and matched with non-refractory IBD controls. We characterized CMV positive patients by assessing laboratory values, concurrent medications, and need for surgery as compared with CMV negative refractory colitis patients.ResultsColonic biopsies from 96 patients were evaluated for CMV; 48 with severe refractory colitis, and 48 non-refractory controls. There was an increased prevalence of CMV in severe refractory colitis [7/48 (14.6%), P < 0.0001]; all were previously CMV negative. Viral DNA burden on immunohistochemistry was not predictive of response to antiviral therapy or need for surgery at 12 months. Lymphopenia was seen in all CMV positive patients, but this did not demonstrate statistical significance (P = 0.09). We did not see an association between azathioprine or infliximab use and the need for surgery at 12 months.ConclusionsThere is an increased prevalence of CMV in colonic biopsies of pediatric patients with severe refractory colitis. Viral burden does not predict clinical outcomes or subsequent need for colectomy.     

Impact of intrarectal chromofungin treatment on dendritic cells-related markers in different immune compartments in colonic inflammatory conditions

BACKGROUNDChromofungin (CHR: chromogranin-A 47-66) is a chromogranin-A derived peptide with anti-inflammatory and anti-microbial properties. Ulcerative colitis (UC) is characterized by a colonic decrease of CHR and a dysregulation of dendritic CD11c⁺ cells.AIMTo investigate the association between CHR treatment and dendritic cells (DCs)-related markers in different immune compartments in colitis.METHODSA model of acute UC-like colitis using dextran sulphate sodium (DSS) was used in addition to biopsies collected from UC patients.RESULTSIntrarectal CHR treatment reduced the severity of DSS-induced colitis and was associated with a significant decrease in the expression of CD11c, CD40, CD80, CD86 and interleukin (IL)-12p40 in the inflamed colonic mucosa and CD11c, CD80, CD86 IL-6 and IL-12p40 within the mesenteric lymph nodes and the spleen. Furthermore, CHR treatment decreased CD80 and CD86 expression markers of splenic CD11c⁺ cells and decreased NF-κB expression in the colon and of splenic CD11c⁺ cells. In vitro, CHR decreased CD40, CD80, CD86 IL-6 and IL-12p40 expression in naïve bone marrow-derived CD11c⁺ DCs stimulated with lipopolysaccharide. Pharmacological studies demonstrated an impact of CHR on the NF-κB pathway. In patients with active UC, CHR level was reduced and showed a negative linear relationship with CD11c and CD86.CONCLUSIONCHR has protective properties against intestinal inflammation via the regulation of DC-related markers and CD11c⁺ cells. CHR could be a potential therapy of UC.     

Influence of receptor activator of nuclear factor kappa B ligand,osteoprotegerin and interleukin-33 on bone metabolism in patients with long-standing ulcerative colitis

BackgroundUlcerative colitis (UC) is a chronic disease with periods of remission and recurrences. Dysfunction of the local immune response leads to chronic inflammation within the large intestine which triggers morphological changes in the intestinal wall as well as induces the synthesis of numerous factors that have an adverse impact on the bone metabolism.The aim of the study was to determine the expression of RANKL, OPG and IL-33 in mucosal biopsies of UC patients with long disease duration as well as serum level of these cytokines in the context of bone density and bone metabolism.Materials and methodsThe UC group consisted of 56 patients with average disease duration of 16 y. The control group comprised 37 healthy individuals. Local expression of cytokines was assessed in the biopsies of colonic mucosa by the real-time PCR and immunohistochemistry (IHC), and their serum concentration was measured by ELISA.ResultsThe increased bone resorption observed in patients with UC was reflected by low bone density and high serum level of C-terminal telopeptide (CTX). Mucosal RANKL expression and serum concentration were similar in UC group and healthy subjects, however, UC patients had higher local expression of OPG and serum OPG concentration. Increased IL-33 gene expression was observed only in UC at the mRNA level. We propose that bone resorption in UC patients despite OPG up-regulation could be caused by IL-33-induced mucosal synthesis of a potent proinflammatory cytokine, such as TNF-α, known as a possible inducer of osteoclastogenesis in the way independent of RANKL.     

Increased HLA-G Expression in Tissue-Infiltrating Cells in Inflammatory Bowel Diseases

Background

Since HLA-G is an immune checkpoint molecule and since Crohn’s disease (CD) and ulcerative colitis (UC) exhibit deregulated immune-mediated mechanisms, we aimed to evaluate intestinal HLA-G expression and soluble HLA-G (sHLA-G) levels in CD/UC patients stratified according to the CD phenotype/localization and UC extension.

Methods

HLA-G tissue expression was assessed by immunohistochemistry in biopsies collected from 151 patients (90 CD, 61 UC) and in surgical resection specimens (28 CD, 12 UC). Surgical material from 24 healthy controls was also assessed. Plasma sHLA-G levels (97 CD, 81 UC, and 120 controls) were evaluated using ELISA.

Results

HLA-G expression was similarly observed in the intestinal epithelial cells of control and CD/UC specimens. However, in biopsies, the plasma cells/lymphocytes infiltrating the lamina propria in CD/UC presented (1) increased HLA-G expression compared to controls (P?<?0.0001), (2) greater cell staining in UC cells than in CD cells irrespective of disease extent (P?=?0.0011), and (3) an increased number of infiltrating cells in the inflammatory CD phenotype compared to that in the stenosing and fistulizing phenotypes (P?=?0.0407). In surgical specimens, CD/UC patients exhibited higher infiltrating cell HLA-G expression in lesion areas than in margins. sHLA-G levels were higher in UC/CD patients (P?<?0.0001) than in controls, but no difference was observed between diseases.

Conclusions

Increased infiltrating cell HLA-G expression associated with increased sHLA-G levels in CD/UC patients may reflect ongoing host strategies to suppress chronic inflammation.

     

Effect of intensive granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis positive for cytomegalovirus

Background and aimCytomegalovirus (CMV) exacerbates ulcerative colitis (UC) refractory to immunosuppressive therapies. The conditions under which CMV reactivation occurs in patients with UC, however, is unclear. In addition, the diagnostic and treatment strategies for UC positive for CMV have not been established. Granulocyte and monocyte adsorptive apheresis (GMAA) is natural biological therapy for UC in which the granulocytes/macrophages producing inflammatory cytokines are removed. We investigated the rate of colonic CMV reactivation and the efficacy of GMAA in active UC patients positive for CMV without concomitant corticosteroid (CS) therapy.MethodsFifty-one active UC patients without concomitant CS therapy were enrolled. Colonic CMV reactivation was examined by real-time polymerase chain reaction (PCR) using biopsy specimen and/or histological examination. All patients were treated with intensive GMAA (twice per week). Rates of clinical remission and mucosal healing were compared between UC patients positive and negative for CMV.ResultsOf 51 patients, 15 (29.4%) were diagnosed as CMV positive. The clinical remission rates following intensive GMAA did not differ between UC patients positive and negative for CMV (73.3% vs 69.4%, p = 0.781). Proportion of patients achieving mucosal healing was also similar between these two groups. CMV-DNA became negative in all UC patients positive for CMV who achieved clinical remission 1 week after completion of intensive GMAA.ConclusionsIntestinal inflammation might trigger CMV reactivation in a subpopulation of active UC patients without CS treatment. GMAA could be a promising option for active UC positive for CMV.     

High frequency of parasitic and viral stool pathogens in patients with active ulcerative colitis: Report from a tropical country

Objective. Diarrhoeal relapses in patients with ulcerative colitis (UC) may be associated with enteric infections and its diagnosis may lessen avoidable exposure to corticosteroids and/or immunosuppressants. The purpose of this study was to assess the frequency of stool pathogens (parasitic and viral) in patients with active UC. Material and methods. This prospective cross-sectional study included 49 consecutive patients (32 M, 17 F, mean age 35.8±12 years) with active UC. Three stool samples were collected from each patient and examined for parasitic infection. Rectal biopsies were obtained during sigmoidoscopy to demonstrate cytomegalovirus (CMV) inclusion bodies and to conduct qualitative polymerase chain reaction (PCR) for CMV and herpes simplex virus (HSV) DNA detection. Results. Median duration of illness was 3.9±3.7 years and 83.7% of the patients had moderate to severe disease. The prevalence of parasitic infections in UC was 12%. The organisms isolated were Strongyloides stercoralis in 4%, Ankylostoma duodenale in 4%, Cryptosporidium in 2% and Entamoeba histolytica in 2% of the patients. The prevalence of CMV and HSV in rectal biopsies using qualitative PCR was 8% and 10%, respectively. No predictive factor was identified with CMV superinfection in patients with active UC. Conclusions. In India there is a high prevalence of parasitic and viral infections in patients with active UC. The results of the study suggest that, in tropical countries with a known high prevalence of parasitic diseases, aggressive evaluation for parasitic and viral infections should be carried out, as early identification and prompt treatment of such infections can improve the clinical course of patients with active UC.     

Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan

AIM： TO investigate active cytomegalovirus （CMV） infection following the cydosporine A （CyA） treatment of steroid-refractory ulcerative colitis （UC）. METHODS： Twenty-three patients with severe UC not responding to steroid therapy （male 14, and female 9） enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA （average 4 mg/kg per day） for 1 mo. Serum and colonic biopsy samples were collected before CyA treatment and 4 d, 10 d, 20 d, and 30 d after treatment. Patients were evaluated for CMV by using serology （IgM antibody by ELISA）, quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin （HE）-stained colonic biopsies. CMV infection was indicated by positive results in any test. RESULTS： No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV （IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients, 78.2%; and inclusion bodies in 4/23 patients, 17.3%）. There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment, leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection （83.3%） required surgical treatment because of severe deteriorating colitis. Treatment with ganciclovir rendered surgery avoidable in three patients. CONCLUSION： Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immunosuppressive therapy.     

Association of PTPN22 gene (rs2488457) polymorphism with ulcerative colitis and high levels of PTPN22 mRNA in ulcerative colitis

Purpose

Our aims were to evaluate protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene polymorphisms in ulcerative colitis (UC) and explore PTPN22 mRNA levels in colonic biopsies of UC patients in central China.

Methods

A total of 165 Chinese UC patients and 300 healthy controls were enrolled in this study. PTPN22 ?1123G/C, +1858C/T, and +788G/A polymorphisms were genotyped by PCR-restriction fragment length polymorphism method. PTPN22 mRNA expressions in colonic biopsies and serum C-reactive protein (CRP) levels were determined by quantitative PCR and immunonephelometry, respectively.

Results

The frequency of C carrier was higher in UC patients than in healthy controls (66.7 vs. 53.3 %, P?=?0.005, odds ratios?=?1.75, 95 % CI 1.18–2.60) and associated with extensive colitis (P?=?0.029). PTPN22 mRNA levels were elevated in UC patients than in healthy controls (P?<?0.001). Among UC patients, PTPN22 mRNA expression levels were higher in biopsies of inflamed colonic tissue compared with noninflamed tissue (P?<?0.001) and were correlated with CRP levels (r?=?0.578, P?<?0.001). PTPN22 mRNA expression levels were elevated in extensive colitis compared to proctitis (P?=?0.008) and to left-sided colitis (P?=?0.029) and were higher in moderate and severe disease than in mild disease (P?=?0.005).

Conclusions

Our study showed the potential association between PTPN22 ?1123G/C polymorphism and UC in central China. PTPN22 mRNA levels were highly expressed in UC, especially in active disease, and were correlated with CRP levels, disease location, and disease severity in UC patients.     

Effects of tissue cytomegalovirus quantitative polymerase chain reaction in the management of ulcerative colitis flare-ups: Should we wave aside?

Background and Study AimsThe role of cytomegalovirus (CMV) infection for disease reactivation in ulcerative colitis (UC) patients remains controversial and diagnostic tests are yet to be standardized. We aimed to define the clinical relevance of CMV detection by mucosal polymerase chain reaction (PCR) in UC patients by comparing the clinical course of UC in CMV-treated and CMV-untreated groups in tissue CMV-PCR positive cases.Patients and MethodsIn this retrospective study, 141 patients diagnosed with moderate-to-severe UC admitted to our clinic with disease flare, colonic tissue CMV PCR was assessed.ResultsThe median age of the study population was 39 years, and 99 (70.2%) patients were male. Eighty-eight (62.4%) patients were CMV-PCR (+) and 53 (37.6%) were CMV PCR (-). The CMV-PCR (+) and CMV PCR (-) groups showed no significant difference concerning age, sex, disease duration, site of involvement and disease activity and administered treatments. The median tissue CMV-PCR was 41,098 IU/mL (IQR:2,344.25–136,192). Thirty-four of 88 CMV-PCR (+) patients received antiviral therapy. The tissue CMV-PCR level of patients who received antiviral therapy was 124,381 IU/mL (IQR: 19,309–412,335), and it was 6,292 IU/mL (IQR: 997–71,154) in patients who did not receive antiviral therapy; (p < 0.001). Sixteen (47.1%) of 34 patients who received antiviral therapy achieved remission. Two of the non-responders underwent colectomy (one because of dysplasia and one who did not respond subsequent biologic agent either). Remaing 16 achieved remission by escalating the immunsuppresive/biologic agent therapy.ConclusionCMV infection is responsible for only a minority of cases of UC flares and all are steroid-resistant cases. Most of the patients non-responsive to antiviral treatment respond to increased anti-inflammatory treatment. Hesitancy in the decision of escalating immunsuppresive treatment rather than CMV disease may be responsible for worsening disease course and increased colectomy rate in a significant number of the patients who are tissue CMV-PCR (+).     

IgG subclasscontaining cells in the human large bowel of normal controls,non-IBD colitis,and ulcerative colitis

IgG subclass-containing cells in colonic mucosa were examined in three groups; 1) normal controls 2) cases of ulcerative colitis (UC) 3) cases of colitis excluding UC and Crohn’s disease (non-IBD colitis) by indirect immunoperoxidase staining method using mouse anti-IgG subclass monoclonal antibodies. The numbers (and proportions) of IgG1, IgG2, IgG3, and IgG4-containing cells in normal colonic mucosa was 80±29/mm² (44.6%), 44±21 (24.1%), 44±24 (23.7%), 13±10 (7.7%), respectively. The proportion of IgG subclass-containing cells in normal colonic mucosa was different from the known proportion of IgG subclass in serum. In UC, the numbers of all IgG subclasses-containing cells were significantly increased compared to controls and non-IBD colitis. However, only IgG1-containing cells were increased in proportion (50.3%) compared to normal controls. In non-IBD colitis, the numbers of IgG1- and IgG2-containing cells were increased compared to the controls, but the increases were less than UC, and there was no difference in the proportion of IgG subclass compared to normal controls. The differences in the numbers and in the proportions of IgG subclass-containing cells between UC and non-IBD colitis may reflect differences in the underlying disease process. This work was partly supported by a grant from the Research Committee for Intractable Intestinal Disease, Ministry of Welfare, Japan.     

G protein-coupled receptor 55 (GPR55) expresses differently in patients with Crohn’s disease and ulcerative colitis

Aim: To investigate the levels of G protein-coupled receptor 55 (GPR55) expression in colonic tissue of inflammatory bowel disease (IBD) patients and healthy controls, and its potential implication in IBD treatment.

Methods: Fifty patients were enrolled in our prospective study: n?=?21 with Crohn’s disease (CD) and n?=?16 with ulcerative colitis (UC); 19 women and 18 men. Control consisted of 13 non-IBD patients. In each subject, two biopsies were taken from different colonic locations. In IBD patients, biopsies both from endoscopically inflamed and non-inflamed areas were drawn and the development of inflammation confirmed in histopathological examination. GPR55 mRNA and protein expression were measured using real-time PCR and Western blot, respectively.

Results: GPR55 expression at mRNA and protein level was detected in all samples tested. The level of GPR55 mRNA expression in non-inflamed colonic areas was comparable in all analyzed groups (p?=?.2438). However, in the inflamed tissues GPR55 mRNA expression was statistically significantly (p?<?.0001) higher (6.9 fold) in CD patients compared to UC. Moreover, CD patients manifested higher (12.5 fold) GPR55 mRNA expression in inflamed compared with non-inflamed colonic tissues (p?<?.0001). Although no significant differences were stated, GPR55 protein level tends to decrease in IBD as compared to control.

Conclusions: Different patterns of GPR55 expression at mRNA level were observed in IBD patients. We speculate that GPR55 is crucial for the mucosal inflammatory processes in IBD, particularly in CD and its expression may affect disease severity, and response to treatment. The GPR55 receptors may become an attractive target for novel therapeutic strategies in IBD.