Ectopic Germinal Centres with B and T Cells and Follicular Dendritic Cell Networks in Urethral Stricture Tissue: Possible Avenue for Immunological Treatments.

BACKGROUND: The underlying cause of a urethral stricture can sometimes be obscure. It is possible that an injury to the urethra induces an immunological cascade that generates scar tissue and fibrosis, eventually resulting in a stricture. If such immunological reactions could be better elucidated, immunological therapies could possibly emerge. OBJECTIVE: To evaluate if ectopic germinal centres exist in urethral stricture disease. DESIGN SETTING AND PARTICIPANTS: Resected stricture specimens from 45 patients undergoing open bulbar urethroplasty with excision and anastomosis were assessed. Histopathological characteristics, such as fibrosis (grade I-III), inflammation, and sclerosis, were evaluated using immunostaining for CD3 (T cells), CD20 (B cells), and CD21 (follicular dendritic cells). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome measure was the presence or absence of a germinal centre. The secondary outcome was evaluation of any correlation between the degree of fibrosis and germinal centres. Fisher's exact test was used for univariate analysis. RESULTS AND LIMITATIONS: In six patients, ectopic germinal centres were found. In ten patients, there was no inflammation at all. There was no correlation found between the degree of fibrosis and the abundance of immunohistochemically detected immune cells. CONCLUSIONS: Ectopic germinal centres, with B and T cells as well as follicular dendritic cell networks, do exist in urethral stricture disease. This finding may open up for novel research avenues on the possibility of adopting immunological treatments for urethral stricture disease. PATIENT SUMMARY: In patients with a narrowing of the urethra due to any kind of trauma, we looked for the presence of centres of immunological reaction in urethral tissue. We identified these immunological centres (also called germinal centres) in some patients. This intriguing finding suggests that immunological treatments may have potential for men with scar tissue in a narrowed urethra.

Cumulative incidence of ureteroenteric strictures after radical cystectomy in a population-based Swedish cohort.

OBJECTIVE: The incidence of benign ureteroenteric strictures following radical cystectomy (RC) for urinary bladder cancer (UBC) is investigated mainly in single-centre studies from high-volume centres. The aim of this study was to evaluate the cumulative incidence of strictures and risk factors in a population-based cohort. PATIENTS AND METHODS: Data was collected from Bladder Cancer Data Base Sweden (BladderBaSe). The primary endpoint was stricture with intervention. Secondary endpoint included hydronephrosis both with/without intervention. RESULTS: In total, 5,816 patients were registered as having had RC due to UBC between 1997 and 2014. After a median follow-up of 23.5 months (IQR = 9.0-63.1 months; range = 0.0-214.0 months), we found that 515 (8.9%) patients underwent intervention for stricture. Seven hundred and sixty-one (13.1%) patients were diagnosed with hydronephrosis without intervention. The cumulative incidence of strictures with intervention was 19.7% (95% CI = 16.7-23.1%) during the 17 years of follow-up. In the first year, the cumulative incidence of strictures was 5.6% (95% CI = 5.0-6.2%), and in the first 2 years 8.4% (95% CI = 7.6-9.3%). For the secondary endpoint, the cumulative incidence was 30.4% (95% CI = 26.7-33.1%) after 17 years. Only the year of RC was associated with stricture incidence in Cox regression analysis, whereas hospital cystectomy volume, patient age and patient sex were not. CONCLUSION: Ureteroenteric strictures requiring intervention may be more common than previously reported, affecting nearly one fifth of patients who have undergone RC for UBC. The annual incidence was highest in the first 2 years after surgery but the cumulative incidence increased continuously during 17 years of follow-up.

Seasonal intestinal inflammation in patients with birch pollen allergy.

BACKGROUND: The pathophysiologic interactions of inflammatory reactions between the mucosa of the respiratory tract and that of the gastrointestinal tract in individuals with allergy are poorly studied, despite the fact that allergic symptoms in the airways and the gastrointestinal tract might arise in the same patient. OBJECTIVE: The objective of this study was to examine the inflammatory response histologically by enumerating eosinophils, IgE+ cells, and T cells in duodenal biopsy specimens in adult patients with IgE-mediated birch pollen allergy during the birch pollen season and off-season. METHODS: Nine patients with birch pollen allergy verified by skin prick test and serum IgE antibodies were investigated toward the end of the birch pollen season and again 6 months later (off-season). Duodenal biopsy specimens were obtained and studied by immunostaining for the eosinophil major basic protein (MBP), IgE, and CD3+ T cells. RESULTS: Oral allergy syndrome to birch-associated foods was present in all patients as indicated by questionnaire. Duodenal increases of MBP+ eosinophils and IgE-bearing cells were found in the patients during the birch pollen season as compared with off-season. No seasonal differences in the T-cell numbers in these patients were seen. Off-season, there was no significant difference between the patients and the control subjects regarding the intestinal frequencies of MBP+ eosinophils, mucosal IgE+ cells, and T cells. CONCLUSION: Birch pollen exposure triggered a local inflammation with an increase in duodenal eosinophils and IgE-carrying mast cells in patients with allergy. Our study gives evidence for the interplay between immunologically active cells in the airways and the gut.

Local allergic reaction in food-hypersensitive adults despite a lack of systemic food-specific IgE.

BACKGROUND: Objective tools are lacking for the diagnosis of local gastrointestinal inflammatory reactions in skin prick test (SPT)-negative and serum IgE antibody (s-IgE Ab)-negative patients with suspected food allergy. OBJECTIVE: The purpose of this investigation was to evaluate the presence of eosinophils, T cells, local IgE-bearing cells, IL-4, and IFN-gamma in small intestinal biopsy specimens from adult SPT-negative/s-IgE Ab-negative patients with food allergy during symptomatic and nonsymptomatic periods. METHODS: Fourteen patients with food allergy-related gastrointestinal symptoms confirmed by double-blinded, placebo-controlled food challenge (DBPCFC) were investigated. Eleven of the patients were SPT-negative and s-IgE Ab-negative. Sex- and age-matched healthy volunteers were used as controls. Duodenal biopsies were studied with immunostaining through use of a panel of mouse monoclonal antibodies specific for eosinophils, CD3, CD4, CD8, IgE, IL-4, and IFN-gamma. RESULTS: Significant increases in numbers of MBP+ eosinophils, IgE-bearing cells, and T cells were found in the duodenal mucosa of the patients when they were symptomatic in comparison with when they were asymptomatic and in comparison with healthy controls. Numbers of IL-4+ cells were increased and numbers of IFN-gamma+ cells were reduced in the patients when they were symptomatic in comparison with when they were asymptomatic and in comparison with the controls. There were no differences in total s-IgE levels between any of the groups. CONCLUSION: A significant correlation was found between the appearance of symptoms of food hypersensitivity and the duodenal presence of IgE-bearing cells, activated eosinophils, and T cells in patients with negative SPT results and negative s-IgE Ab to the offending food. We suggest that a localized IgE-mediated response caused the gastrointestinal symptoms seen in these patients.