B1a Lymphocytes (CD19+CD5+) Deficiency in Patients with Crohn’s Disease and Its Relation with Disease Severity

2018 ◽  
Vol 36 (3) ◽  
pp. 194-201 ◽  
Author(s):  
Rafael Gil-Borras ◽  
Carlos García-Ballesteros ◽  
Carmen Benet-Campos ◽  
Ignacio Catalán-Serra ◽  
Francisca López-Chuliá ◽  
...  

Background/Aims: B1a cells (CD19+CD5+) are considered elements of the innate immune system. The aim of this study was to evaluate the frequency of B1a cells in the peripheral blood of patients with Crohn’s disease (CD) and its relation with disease severity. Methods: In this prospective study, a total of 128 subjects (64 CD patients and 64 healthy controls) were studied. B1a cells in peripheral blood, CD Activity Index, and Simple Endoscopic Score of B1a cells were studied. Results: A significant decrease of B1a cells in peripheral blood was observed in patients with CD versus controls (p = 0.002), especially in perforating or penetrating patterns (p = 0.017). A lower frequency of B1a cells is related to increased endoscopic severity (Spearman’s Rho: –0.559, p = 0.004). The mean frequency of B1a cells in patients with pre- and post-study surgery was significantly lower than that in patients who did not undergo surgery (p = 0.050 and p = 0.026, respectively). Conclusions: The B1a cell count in peripheral blood is lower in CD patients. This decrease is directly related to the severity of the disease (penetrating or perforating, Simple Endoscopy Score and surgery complication). These results pointed to the fact that B1a cells play an important role in immune protection in CD.

2020 ◽  
Author(s):  
Su-Mi Lee ◽  
Kyung-Hwa Lee ◽  
Seon-Young Park ◽  
Jin Ook Chung ◽  
Dong Hyun Kim ◽  
...  

Abstract Backgrounds: Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn’s disease (CD).Methods: Endoscopic samples were identified from 83 CD patients with and 372 controls without any pathologic findings by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. Results: The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P<0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P=0.01). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend=0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95%CI 0.20~0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P=0.03). Conclusions: Cyr61 mucosal expression in CD patients was inversely associated with clinical course. In the future, the possible therapeutic role of Cyr61 should be considered.


2020 ◽  
Author(s):  
Juanjuan Zhang ◽  
Zhen Guo ◽  
Yanqing Diao ◽  
Binlin Da ◽  
Zhiming Wang ◽  
...  

Abstract Background: Intestinal stricture is a complication of Crohn’s disease (CD) due to fibrosis, but there are no biomarkers for predicting intestinal strictures before clinical obstruction. It is reported that several types of lymphocytes (LC) are involved in the pathogenesis of intestinal fibrosis. However, few studies have focused on the peripheral blood LC in patients with CD associated stricture.Aim:To analyze the relationships between peripheral blood inflammatory markers especially LC and CD to provide evidence for CD diagnosis and therapy. Methods: A total of 158 CD patients who underwent single-balloon enteroscopy from January 2016 to June 2019 in Jinling Hospital were retrospectively enrolled. The Montreal classification, maintenance medicines, CD activity index (CDAI), simple endoscopic score for CD (SES-CD), full blood count and C-reactive protein (CRP) level were recorded. The relationships among peripheral blood inflammatory markers, disease activity and intestinal strictures were analyzed using SPSS 22.0. Results: After excluding 8 patients treated with azathioprine, which severely affects blood counts, 150 patients were divided into two groups: a stricture group (n=82) and non-stricture group (n=68). LC and the proportion of lymphocytes (LC%) were significantly lower in the stricture group than in the non-stricture group, p was 0.000 and 0.018, respectively, and LC was an independent risk factor of stricture lesion. In the subgroup analysis, 30 strictures without obstruction were classified as mild strictures, and 52 cases of obstruction were in the severe stricture group. LC notably decreased following stricture aggravation, p=0.000. The area under the curve (AUC) of LC predicting strictures was 0.711 with sensitivity of 73.5% and a specificity of 63.4% (cutoff: 1.245). Conclusion: LC gradually decreases as intestinal strictures aggravated and could be a new marker for predicting intestinal strictures in CD patients.


Author(s):  
James D Lewis ◽  
Paul Rutgeerts ◽  
Brian G Feagan ◽  
Geert D’haens ◽  
Silvio Danese ◽  
...  

Abstract Background The Crohn’s Disease Activity Index (CDAI) has been criticized for being weakly correlated with bowel inflammation. We assessed correlation between Simple Endoscopic Score for Crohn’s Disease (SES-CD) and individual CDAI items stratified by disease location to better understand this relationship. Methods We pooled patient-level data from 3 placebo-controlled Crohn’s disease (CD) trials that tested adalimumab, upadacitinib, and risankizumab. Disease location was defined as ileum only, colon only, or ileocolonic based upon colonoscopy at study entry. Pearson correlation coefficients and linear regression assessed correlations between items of the CDAI and SES-CD. Results A total of 353 patients were included (20.7% ileal, 30.6% colonic, 48.7% ileocolonic disease). Crohn’s Disease Activity Index and SES-CD scores were moderately correlated (R = 0.33; P < 0.001). Among CDAI items, the strongest correlations with SES-CD were seen with very soft or liquid stool frequency (SF) and patient-reported outcome 2 (PRO2; which includes SF and abdominal pain score; both R = 0.36; P < 0.001); these correlations were numerically stronger in colonic disease (SF: R = 0.46; P < 0.001; PRO2: R = 0.44; P < 0.001) than in ileal disease (SF: R = 0.14; P = 0.23; PRO2: R = 0.21; P = 0.07), although a test for interaction was not significant. In adjusted linear regression models, the proportion of mucosa that was inflamed and the proportion of mucosa with ulceration were positively correlated, whereas the presence of strictures was inversely correlated with SF. Conclusions The SF item of the CDAI is moderately correlated with SES-CD and independently correlated with mucosal ulceration, inflammation, and strictures. Understanding why bowel inflammation as measured endoscopically does not correlate more strongly with patients’ symptoms could help develop scales that link CD pathology to patient experience.


2020 ◽  
Author(s):  
Su-Mi Lee ◽  
Kyung-Hwa Lee ◽  
Seon-Young Park ◽  
Jin Ook Chung ◽  
Dong Hyun Kim ◽  
...  

Abstract Backgrounds: Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn’s disease (CD).Methods: Endoscopic samples were identified from 83 CD patients with and 372 controls without any pathologic findings by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. Results: The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P<0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P=0.01). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend=0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95%CI 0.20~0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P=0.03). Conclusions: Cyr61 mucosal expression in CD patients was inversely associated with clinical course. In the future, the possible therapeutic role of Cyr61 should be considered.


2021 ◽  
Author(s):  
Su-Mi Lee ◽  
Kyung-Hwa Lee ◽  
Seon-Young Park ◽  
Jin Ook Chung ◽  
Dong Hyun Kim ◽  
...  

Abstract Backgrounds: Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn’s disease (CD).Methods: Endoscopic samples were identified from 83 CD patients with and 372 controls by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. We also measured the level of mRNA for Cyr 61 and proinflammatory genes in inflamed and noninflamed colonic mucosal lesions from CD patients.Results: The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P<0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P=0.01). Cyr61 mRNA levels in inflamed mucosa were 2-fold higher than those in non-inflamed lesion (P>0.05) and the mRNA levels of IL-6 and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa in CD patients (all P<0.05). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend=0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95%CI 0.20~0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P=0.03).Conclusions: Cyr61 mucosal expression in CD patients was inversely associated with clinical course. Future study need to be considered to evaluate whether Cyr 61 may play a role in activating inflammatory responses and contributing to wound healing and tissue repair in patients with CD.


2011 ◽  
Vol 152 (14) ◽  
pp. 546-554 ◽  
Author(s):  
Judit B. Kovács ◽  
Anikó Nagy ◽  
András Szabó ◽  
Margit Lőrincz

Objective: To assess the characteristics and course of childhood-onset Crohn’s disease among Hungarian patients. Methods: Records of 81 patients admitted between 1984 and 2006 and treated at least for one year until the 18th year of age were reviewed. Results: There was a 62% male dominance and a rate of 12.5% of familial cases. The diagnostic lag was 11.36 (1–96) months. The mean age was 13.6 years (4–17), the activity index was 37.88 (5–80) at diagnosis and the initial frequencies were as follows: ileal affection 87%, stricturing and penetrating forms 27%, perianal manifestation 26%, giant cells or granuloma formation 47%, malnutrition 23,5%, growth failure 11%. Steroid therapy and azathioprin treatment were given in 84% and 62% of the patients, respectively. Biologic treatment was not possible during the study period. 31% of the patients underwent surgery (abdominal surgery 20%, perianal surgery 11%). When patients reached the 18th year of age the mean activity index decreased to 6.63 (0–35), the rate of malnutrition to 9.9% and that of growth failure to 2.5%. All these changes were statistically significant. Conclusions: Characteristics of childhood-onset Crohn’s disease in Hungary are similar to those obtained in other European countries. The prolonged diagnostic lag, the high initial activity index, the granuloma formation and the stricturing/penetrating behavior may predict subsequent complications and need for surgery, and, therefore, justify intense initial therapy. The early introduction of immunomodulatory therapy affects favorably the course of illness. Orv. Hetil., 2011, 152, 546–554.


Author(s):  
Ahmad Haider ◽  
Winfried Kurtz ◽  
Erik J. Giltay ◽  
Louis J. Gooren ◽  
Farid Saad

AbstractBoth elevated and depressed testosterone (T) levels have been reported in Crohn's disease (CD). In this pilot study, effects of T administration on CD were assessed.A total of 13 men with CD, aged 45–67 years, had subnormal plasma T (mean±SD=9.0±1.4 nmol/L) (reference >12.0); they were compared to a group of 110 men of similar age with sexual and urological problems whose plasma T was also subnormal: 10.4±1.4 nmol/L (p=0.02). All received treatment with parenteral T undecanoate for 24 months. The Crohn's Disease Activity Index (CDAI) was assessed as an indicator of the severity of the disease every 3 months. Levels of T and C-reactive protein (CRP) were compared between the 13 men with CD and the other men in this study. Values of CDAI and CRP were followed-up.CRP levels were 22.7 mg/dL (95% confidence interval of the mean: 14.9–34.3) in the 13 men with CD vs. 3.5 (2.9–4.1) in 107 control men (p=0.001). Upon normalization of serum T, there was a significant decline of CDAI (from 243±19 to 89±9), CRP levels from 22.7±8.1 to 6.9±2.9 mg/dL, and white blood cell count. Hemoglobin/hematocrit increased significantly.Upon normalization of plasma T the CDAI and CRP levels decreased in hypogonadal patients with CD. The mechanism of this improvement could be through immunosuppressive effects of T, reducing chronic inflammation of the intestinal wall in CD.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 109-111
Author(s):  
H Ma ◽  
D Migliarese Isaac ◽  
A Petrova ◽  
D Parsons ◽  
K Anna ◽  
...  

Abstract Background Previous research has shown that transabdominal bowel ultrasound (TABUS) can detect disease in inflammatory bowel disease (IBD) patients. Aims Our aim is to determine the parameters of bowel ultrasound findings that are associated with disease severity at time of diagnosis. Methods This prospective study was conducted at the Stollery Children’s Hospital in Edmonton, Alberta. Patients with suspect IBD were enrolled. Each patient underwent a baseline ultrasound, Physicians performed TABUS to visualize the small and large intestine (except rectum). Other investigations including blood work, MRI, and endoscopy. Disease severity in was categorised into mild, moderate and severe using the weighted pediatric Crohn’s disease activity index (wPCDAI), simple endoscopic score for CD (SES-CD), pediatric ulcerative colitis disease activity index (PUCAI), and Mayo score in UC. The severity of disease was compared to 7 ultrasound parameters (fat proliferation, hyperemia, bowel wall thickness (BWT), free intra- abdominal fluid, &gt; 4 lymph nodes (LN) in an area, presence of stricture, and BW stratification. Data was analyzed using SPSS. Anova and Chi square were used to determine parameters for TABUS that were associated with disease severity, with p &lt;0.05 considered significant. Results This prospective study was conducted at the Stollery Children’s Hospital in Edmonton, Alberta. Patients with suspect IBD were enrolled. Each patient underwent a baseline ultrasound, Physicians performed TABUS to visualize the small and large intestine (except rectum). Other investigations including blood work, MRI, and endoscopy. Disease severity in was categorised into mild, moderate and severe using the weighted pediatric Crohn’s disease activity index (wPCDAI), simple endoscopic score for CD (SES-CD), pediatric ulcerative colitis disease activity index (PUCAI), and Mayo score in UC. The severity of disease was compared to 7 ultrasound parameters (fat proliferation, hyperemia, bowel wall thickness (BWT), free intra- abdominal fluid, &gt; 4 lymph nodes (LN) in an area, presence of stricture, and BW stratification. Data was analyzed using SPSS. Anova and Chi square were used to determine parameters for TABUS that were associated with disease severity, with p &lt;0.05 considered significance. Conclusions Fat proliferation was found to be associated with severity of Crohn’s disease based on disease activity score while BWT was associated with endoscopic severity. Lack of association in UC is likely due to the low number of patients recruited. Funding Agencies WCHRI Capacity Grant


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Marcin Kucharski ◽  
Jacek Karczewski ◽  
Dorota Mańkowska-Wierzbicka ◽  
Katarzyna Karmelita-Katulska ◽  
Elżbieta Kaczmarek ◽  
...  

Background. Assessment of endoscopic activity of Crohn’s disease (CD) is of growing importance both in clinical practice and in clinical trials. The study aimed to assess which of the endoscopic indices used for evaluation of mucosal changes correlates with the currently used clinical indices for determination of disease activity and with the results of histopathological examination.Study. A group of 71 patients with CD and 52 individuals without a diagnosis of GI tract disease as a control group were investigated, considering clinical and histological severity of the disease and the severity of inflammatory changes in the bowel. Evaluation was conducted with the use of clinical, endoscopic, and histopathological indices. Endoscopic indices were then correlated with different clinical and histopathological indices with the aim of finding the strongest correlations.Results and Conclusions. Correlation between the clinical disease activity and the severity of endoscopic lesions in CD was shown in this study to be poor. The results also indicate that the optimal endoscopic index used in the diagnostic stage and in the assessment of treatment effects in CD is Simple Endoscopic Score for Crohn’s Disease (SES-CD).


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jia-yin Yao ◽  
Min Zhang ◽  
Wei Wang ◽  
Xiang Peng ◽  
Jun-zhang Zhao ◽  
...  

Abstract Background Ustekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn’s disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze the UST exposure–response relationship in CD treatment in the real-world setting. Methods We retrospectively enrolled patients with CD who received UST between March 1, 2020 and May 31, 2021, at the inflammatory bowel disease (IBD) center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by the Crohn’s disease activity index (CDAI), and endoscopic outcomes evaluated using a simple endoscopic score for Crohn’s disease (SES-CD) at week 16/20 were collected. The optimal UST cut-off trough concentration was identified using receiver operating characteristic curve (ROC) analysis. Results Nineteen eligible patients were included in the study, the mean age was 29.1 ± 9.1 years and the mean disease duration was 5.5 ± 4.7 years. At the initiation of the study, 89.5% of the patients had been exposed to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had perianal diseases. At week 16/20 after the UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration for UST was 1.12 μg/mL, as determined by the ROC with an area under the curve (AUC) of 0.78, sensitivity of 87.5%, and specificity of 72.7%. Patients with a UST trough concentration > 1.12 μg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P = 0.02). Conclusions UST is an effective therapeutic option for refractory CD treatment. A UST trough concentration above 1.12 μg/mL was associated with endoscopic remission at week 16/20 after UST initiation. Trial registration This study was approved and retrospectively registered by the Ethics Committee of Sun Yat-Sen University (2021ZSLYEC-066, March 29, 2021) and the Clinical Trial Registry (NCT04923100, June 10, 2021).


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