The role of CD40 in ulcerative colitis: histochemical analysis and clinical correlation

Polese, Lino; Angriman, Imerio; Cecchetto, Attilio; Norberto, Lorenzo; Scarpa, Marco; Ruffolo, Cesare; Barollo, Michela; Sommariva, Antonio; D’Amico, Davide

doi:10.1097/00042737-200203000-00006

Cited by 38 publications

(30 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…First, pretreatment of mice with a blocking anti-CD40 Ab completely inhibited SMX-NO immunogenicity; second, treatment of human lymphocytes from healthy SMX naive volunteers with a stimulatory anti-CD40 Ab and SMX-NO enhanced the strength of the recall proliferative response with SMX-NO; and third, increased dendritic cell CD40 expression was 5-fold higher when cells from a patient in the acute phase of a SMX hypersensitivity reaction was compared with cells from four SMX-exposed healthy volunteers. Although this is only from one patient, it is consistent with diseases such as ulcerative colitis where the extent of disease activity has been found to be proportional to CD40 expression levels (77).…”

Section: Discussionsupporting

confidence: 83%

Sulfamethoxazole and Its Metabolite Nitroso Sulfamethoxazole Stimulate Dendritic Cell Costimulatory Signaling

Sanderson

Naisbitt

Farrell

et al. 2007

The Journal of Immunology

117

107

View full text Add to dashboard Cite

Different signals in addition to the antigenic signal are required to initiate an immunological reaction. In the context of sulfamethoxazole allergy, the Ag is thought to be derived from its toxic nitroso metabolite, but little is known about the costimulatory signals, including those associated with dendritic cell maturation. In this study, we demonstrate increased CD40 expression, but not CD80, CD83, or CD86, with dendritic cell surfaces exposed to sulfamethoxazole (250–500 μM) and the protein-reactive metabolite nitroso sulfamethoxazole (1–10 μM). Increased CD40 expression was not associated with apoptosis or necrosis, or glutathione depletion. Covalently modified intracellular proteins were detected when sulfamethoxazole was incubated with dendritic cells. Importantly, the enzyme inhibitor 1-aminobenzotriazole prevented the increase in CD40 expression with sulfamethoxazole, but not with nitroso sulfamethoxazole or LPS. The enzymes CYP2C9, CYP2C8, and myeloperoxidase catalyzed the conversion of sulfamethoxazole to sulfamethoxazole hydroxylamine. Myeloperoxidase was expressed at high levels in dendritic cells. Nitroso sulfamethoxazole immunogenicity was inhibited in mice with a blocking anti-CD40L Ab. In addition, when a primary nitroso sulfamethoxazole-specific T cell response using drug-naive human cells was generated, the magnitude of the response was enhanced when cultures were exposed to a stimulatory anti-CD40 Ab. Finally, increased CD40 expression was 5-fold higher on nitroso sulfamethoxazole-treated dendritic cells from an HIV-positive allergic patient compared with volunteers. These data provide evidence of a link between localized metabolism, dendritic cell activation, and drug immunogenicity.

show abstract

Section: Discussionsupporting

confidence: 83%

Sulfamethoxazole and Its Metabolite Nitroso Sulfamethoxazole Stimulate Dendritic Cell Costimulatory Signaling

Sanderson

Naisbitt

Farrell

et al. 2007

The Journal of Immunology

117

107

View full text Add to dashboard Cite

show abstract

“…The hypothesis of a pathogenic role of up-regulation of costimulatory molecules in the loss of tolerance in the large bowel mucosa of patients affected by IBD has been assessed in several studies (9,(14)(15)(16), and to understand its meaning we quantified the mucosal expression of CD80 and CD86 in relation to clinical and biochemical parameters of UC patients.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study we demonstrated that the expression of CD40 on leukocytes in the colonic mucosa of patients with UC is significantly increased and proportional to the state of activity (16). Furthermore, up-regulated CD86 expression was demonstrated on non-professional APC like colonic epitelial cells in UC patients.…”

mentioning

confidence: 81%

The Role of Costimulatory Molecules CD80 and CD86 and IFNγ in the Pathogenesis of Ulcerative Colitis

et al. 2004

Self Cite

View full text Add to dashboard Cite

Several studies showed that costimulatory signals on antigen presenting cells are up-regulated in inflammatory bowel disease. We quantified the expression of CD80, CD86, and IFNgamma in colonic mucosa of patients affected by ulcerative colitis and correlated it with clinical and biochemical parameters to identify the context of this up regulation. We enrolled 21 patients affected by ulcerative colitis and 6 healthy subjects. We evaluated for each patient gender, age, duration of disease, clinical, endoscopic and histologic disease activity index, medical therapy, ESR, serum CRP, WBC, and serum al-acid glycoprotein. CD80, CD86, and IFNgamma expression in the colonic mucosa was quantified using reverse transcription polymerase chain reaction. Statistical analysis was performed using Mann-Whitney U test and Spearman's rank correlation test. Significance was set at P < 0.05. CD80 was detectable in seven patients, while CD86 and IFNgamma expression was evident in all UC patients. CD80 and CD86 were not detectable in control specimens. Colonic CD80 expression was correlated to the age of the patients. CD86 expression showed an inverse correlation with duration of disease and a direct correlation with serum CRP levels and histologic grade of disease activity. IFNgamma was not correlated with any of the examined parameter. Our study confirms a major role in ulcerative colitis pathogenesis for CD86 which correlates with histologic grade of disease and with serum CRP levels, and its upregulation seems to be higher at the beginning of the disease. In "in vivo" conditions IFNgamma may not be the only factor responsible for CD86 up-regulation in the ulcerative colitis colonic mucosa.

show abstract

“…Battaglia et al [19], Polese et al [20], and Vogel et al [21] confirmed immunohistochemically that the actively inflamed intestinal wall of UC or CD patients contains mononuclear, endothelial, and mesenchymal cells showing strong expression of CD40, scattered both in the mucosal and submucosal membrane [19,20,21]. In the study by Polese et al [20], the number of CD40-positive cells in the colonic mucosa of UC patients was markedly elevated and correlated with disease activity determined on the basis of clinical, endoscopic, and histological criteria. There were statistically significant differences between UC and IBD patients (p<0.005), even when these 2 groups were compared during the period of remission (p<0.05).…”

Section: Discussionmentioning

confidence: 99%

“…Studies conducted by Danese et al [18], Battaglia et al [19], Polese et al [20], and Vogel et al [21], using immunohistochemical methods to analyze the distribution of CD40 within the normal mucosa of the large intestine, revealed the expression of this molecule only in solitary mononuclear cells of the mucosal lamina propria, as well as in the endothelial cells of submucosal microcirculation. In contrast, the expression of CD40 was not detected in the cells of mucosal muscle layer, and in the mesenchymal cells of submucosal membrane.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of CD40 and CD80 receptors in the colonic mucosal membrane of children with inflammatory bowel disease

Kamińska

Roszko-Kirpsza

Landowski

et al. 2015

Ann Agric Environ Med.

View full text Add to dashboard Cite

Introduction. The most prevalent inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn's disease (CD). Immune processes play a vital role in the etiopathogenesis of these conditions, involving both cellular and humoral response mechanisms. The aim of this study was to quantify CD40-and CD80-positive cells in the biopsy specimens of large intestinal mucosa from children with IBD. Materials and method. The study comprised 38 children aged between 3-17 years (mean 11.5±3.7 years) -20 boys (52.6%) and 18 girls (47.4%). Eighteen patients were diagnosed with UC on the basis of clinical manifestation, endoscopic and histopathological findings. Mean age of this subgroup was 11.55±4.07 years. A group of 10 children (mean age 12.30±2.83) diagnosed with CD was also included. The control group comprised 10 IBD-free children (mean age 10.28±4.07 years). The surface expressions of CD40 and CD80 were analyzed in large intestine mucosa biopsy specimens, fixed in formaldehyde, embedded in paraffin, and cut with a microtome into 4 µm slices. Results. The number of CD40-and CD80-positive cells in the large intestinal mucosa of children with Crohn's disease and ulcerative colitis was significantly higher than in the controls. The highest number of CD40+ and CD80+ cells was observed in the caecal mucosal membrane of Crohn's disease patients and in the rectal mucosa of individuals with ulcerative colitis. Conclusion. IBD is characterized by elevated, segment-specific, expression of CD40 and CD80.

show abstract

The role of CD40 in ulcerative colitis: histochemical analysis and clinical correlation

Abstract: The expression of CD40 in the colonic mucosae of patients with ulcerative colitis is significantly increased and is proportional to the state of activity. The results seem to confirm the hypothesis that a loss of tolerance could be involved in the pathogenesis of this disease.

Cited by 38 publications

References 23 publications

Sulfamethoxazole and Its Metabolite Nitroso Sulfamethoxazole Stimulate Dendritic Cell Costimulatory Signaling

Sulfamethoxazole and Its Metabolite Nitroso Sulfamethoxazole Stimulate Dendritic Cell Costimulatory Signaling

The Role of Costimulatory Molecules CD80 and CD86 and IFNγ in the Pathogenesis of Ulcerative Colitis

Evaluation of CD40 and CD80 receptors in the colonic mucosal membrane of children with inflammatory bowel disease

Contact Info

Product

Resources

About