Association between vitamin D serum levels and disease activity markers in patients with Crohn’s Disease

Abstract Background In patients with inflammatory bowel disease (IBD), up to 30% do not achieve response, 66% do not achieve remission, and 40% experience loss of response to anti-TNFα treatment. In Crohn’s disease (CD), fecal calprotectin is the most widely used fecal biomarker for diagnosis and monitoring of disease activity. Fecal sampling and processing are tedious compared to serum sampling, and biomarker quantification in serum is more efficient, convenient, and also more acceptable for patients. Therefore, there is a need for a robust and reliable serum calprotectin biomarker that performs better than conventional serum biomarkers. The aim of this study was to investigate the performance of a novel serum calprotectin assay, which quantifies a specific human neutrophil elastase (HNE) generated calprotectin (S100a9) fragment (CPa9-HNE), as a measure of true neutrophil granulocyte activity, for monitoring treatment responses in patients with CD. Methods We included 30 CD patients with clinically active (Harvey-Bradshaw Index (HBI)≥5) luminal inflammation scheduled for anti-TNF treatment (adalimumab or infliximab). Serum samples where obtained at baseline (n=30), week 1 (n=29), week 8 (n=28), week 26 (n=15), and week 56 (n=7). CPa9-HNE (Calprotectin, S100a9, specific fragment generated by human neutrophil elastase), CRP and fecal calprotectin were quantified. Remitters (n=11) were defined as patients in clinical remission (HBI<5) at week 8 with no flares at week 26 or week 56. Non-remitters (n=19) were defined by having clinical active disease (HBI≥5) at week 8 or having a flare at week 26 or week 56. Results Patients with severe disease activity (HBI>16) had significantly elevated serum levels of CPa9-HNE compared with patients in remission (p<0.05), with mild (p<0.05) or moderate (p<0.01) disease activity. CPa9-HNE serum levels were significantly suppressed in remitters compared with non-remitters at week 8 (p<0.001), week 26 (p<0.01) and week 56 (p<0.05) (Figure 1). Fecal calprotectin and CRP were significantly suppressed at week 8, week 26 and week 56 compared with baseline levels for remitters and non-remitters, but there was no significant difference between remitters and non-remitters (Figure 1). Non-remitters were more likely to have high levels of CPa9-HNE at baseline (tertile 1,2 vs tertile 3; OR: 6.8 (CI:1.22-36.5), p=0.027) and week 8 (tertile 1,2 vs tertile 3; OR: 24 (CI:2.56-279), p=0.0014). Conclusion CPa9-HNE is a novel non-invasive biomarker for monitoring treatment response to anti-TNFα for CD patients and may be used as a surrogate marker for assessing disease activity and to predict outcome of anti-TNFα treatment.

Download Full-text

Elevated Levels of IL-27 Are Associated with Disease Activity in Patients with Crohn’s Disease

Mediators of Inflammation ◽

10.1155/2021/5527627 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Xiufang Cui ◽

Chunhua Jiao ◽

Di Wang ◽

Ziping Ye ◽

Jingjing Ma ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Clinical Significance ◽

Activity Index ◽

Biological Marker ◽

Disease Activity Index ◽

Serum Levels ◽

Th1 Cells ◽

Control Subjects

Immune disorders play an important role in the pathogenesis of Crohn’s disease (CD). Notably, the increased immune response of Th1 cells and related cytokines is associated with the onset of CD. IL-27 is a newly discovered IL-12-related cytokine, but its expression and clinical significance in CD patients are still controversial. This study is aimed at evaluating the serum levels of IL-27 in CD patients and analyzing their clinical significance. The results indicated that serum levels of IL-27 in CD patients were significantly higher than those in control subjects (median (interquartile range (IQR)): 110.0 (95.0, 145.0) vs. 85.0 (80.0, 95.0) pg/ml, P < 0.001 ). Furthermore, the IL-27 levels significantly increased in CD patients at the active stage compared with CD patients in remission (CDR) (127.5 (100.0, 150.0) vs. 90 (80.0, 110.0) pg/ml, P < 0.001 ). However, there was no difference in IL-27 levels between CDR and control subjects. The levels of IL-27 were positively correlated with Crohn’s disease activity index (CDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), and Simple Endoscopic Score for Crohn’s Disease (SES-CD) and negatively correlated with hemoglobin (Hb) and serum albumin (ALB). IL-27 combined with CRP favored the prediction of CD activity (area under the curve (AUC): 0.88). Additionally, the proportions of Th17 and Th1 cells in peripheral blood were higher in CD patients than in control subjects. Active CD patients exhibited significantly higher proportions of Th17 and Th1 cells than those in remission. Moreover, correlation analysis indicated that the serum levels of IL-27 were positively associated with the frequency of Th17 cells in CD patients ( r = 0.519 , P = 0.013 ) but not associated with the frequency of Th1 cells in CD patients. IL-27 is positively associated with multiple inflammation indicators and may exert a proinflammatory profile by regulating Th17 cell differentiation in the development of Crohn’s disease. In the future, IL-27 combined with CRP is expected to become an important biological marker of CD activity.

Download Full-text

Clinical evaluation of vitamin D status and its relationship with disease activity and changes of intestinal immune function in patients with Crohn’s disease in the Chinese population

Scandinavian Journal of Gastroenterology ◽

10.1080/00365521.2020.1844793 ◽

2020 ◽

Vol 56 (1) ◽

pp. 20-29

Author(s):

Yan Yang ◽

Xiufang Cui ◽

Jiajia Li ◽

Haiyang Wang ◽

Yi Li ◽

...

Keyword(s):

Vitamin D ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Immune Function ◽

Clinical Evaluation ◽

Chinese Population ◽

Vitamin D Status

Download Full-text

The Association of Vitamin D Status with Disease Activity in a Cohort of Crohn’s Disease Patients in Canada

Nutrients ◽

10.3390/nu9101112 ◽

2017 ◽

Vol 9 (10) ◽

pp. 1112 ◽

Cited By ~ 15

Author(s):

Dania Alrefai ◽

Jennifer Jones ◽

Wael El-Matary ◽

Susan Whiting ◽

Abdulrahman Aljebreen ◽

...

Keyword(s):

Vitamin D ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Vitamin D Status

Download Full-text

Serum Syndecan-1 Levels and Its Relationship to Disease Activity in Patients with Crohn’s Disease

Gastroenterology Research and Practice ◽

10.1155/2015/850351 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Cem Çekiç ◽

Adnan Kırcı ◽

Sezgin Vatansever ◽

Fatih Aslan ◽

Huriye Erbak Yılmaz ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Activity Index ◽

Normal Population ◽

Disease Activity Index ◽

Serum Levels ◽

Control Group ◽

Serum Samples ◽

Reactive Protein

Background. Syndecan-1 (SDC-1), a member of the family of heparan sulfate proteoglycans, plays an important role in the resolution of inflammation. This study aimed to investigate the relationship between SDC-1 and disease activity in Crohn’s disease (CD).Methods. Serum samples of 54 patients with CD and 30 healthy controls were obtained. First, SDC-1 levels of the CD patients were compared to the control group. Subsequently, SDC-1 levels were analyzed in patients with CD in active and remission periods. Finally, SDC-1 efficacy in predicting disease activity was evaluated by performing correlation analysis between SDC-1 and C-reactive protein (CRP) and Crohn’s disease activity index (CDAI).Results. SDC-1 level was higher in the CD group (61.9 ± 42.6 ng/mL) compared with the control group (34.1 ± 8.0 ng/mL)p=0.03. SDC-1 levels were higher in active CD patients (97.1 ± 40.3 ng/mL) compared with those in remission (33.7 ± 13.5 ng/mL)p<0.001. A significant positive correlation was found between SDC-1 and CRP (r=0.687,p<0.001) and between SDC-1 and CDAI (r=0.747,p<0.001).Conclusion. Serum levels of SDC-1 are higher in CD compared to the normal population and can be an effective marker of disease severity.

Download Full-text

Vitamin D deficiency is associated with disease activity in patients with Crohn’s disease

Intestinal Research ◽

10.5217/ir.2018.00022 ◽

2019 ◽

Vol 17 (1) ◽

pp. 70-77 ◽

Cited By ~ 5

Author(s):

Kyoung Ho Ko ◽

You Sun Kim ◽

Bo Kyung Lee ◽

Jong Hyun Choi ◽

Yong Moon Woo ◽

...

Keyword(s):

Vitamin D ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Vitamin D Deficiency

Download Full-text

Vitamin D Deficiency Is Associated with Endoscopic Severity in Patients with Crohn’s Disease

Gastroenterology Research and Practice ◽

10.1155/2017/4869718 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 8

Author(s):

Lingna Ye ◽

Ziwen Lin ◽

Jing Liu ◽

Qian Cao

Keyword(s):

Vitamin D ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Vitamin D Deficiency ◽

Activity Index ◽

Disease Activity Index ◽

Vitamin D Status ◽

Serum 25Ohd ◽

Vitamin D Levels

Background and Aims. Vitamin D deficiency is common in patients with Crohn’s disease and is associated with disease activity. Relationship between vitamin D and endoscopic disease activity is unknown. The aim of the study is to determine the association between vitamin D status and endoscopic disease activity in CD patients.Methods. Consecutive hospitalized CD patients from 2014 to 2016 who received vitamin D assessment and colonoscopy were retrospectively evaluated. Clinical disease activity was assessed by Crohn’s disease activity index and C-reactive protein. Endoscopic activity was calculated using simple endoscopic score for Crohn’s disease.Results. Median serum 25OHD level of 131 patients was lower than healthy controls [21.1 nmol/L (11.8–32.3) versus 49.9 nmol/L (44.9–57.4),P=0.007]. 125 (95%) patients had vitamin D deficiency and the rest (5%) had vitamin D insufficiency. Serum 25OHD was inversely correlated with CRP (r=−0.308,P<0.001), CDAI (r=−0.582,P<0.001), SES-CD (r=−0.294,P=0.001), and endoscopic severity stratified by SES-CD (P=0.001).Conclusion. Vitamin D deficiency was prevalent among hospitalized CD patients. Vitamin D levels were inversely correlated with endoscopic disease activity. Vitamin D status could be a biomarker in assessing disease activity among hospitalized CD patients in addition to CDAI and CRP.

Download Full-text

Vitamin D Deficiency Increases the Risk for Moderate to Severe Disease Activity in Crohn's Disease Patients in South Africa, Measured by the Harvey Bradshaw Index

Journal of the American College of Nutrition ◽

10.1080/07315724.2015.1039665 ◽

2015 ◽

Vol 35 (2) ◽

pp. 163-174 ◽

Cited By ~ 11

Author(s):

Abigail Raffner Basson ◽

Rina Swart ◽

Esme Jordaan ◽

Mikatako Mazinu ◽

Gillian Watermeyer

Keyword(s):

South Africa ◽

Vitamin D ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Vitamin D Deficiency ◽

Severe Disease

Download Full-text

A New Model Based on 25-Hydroxyvitamin D3 for Predicting Active Crohn’s Disease in Chinese Patients

Mediators of Inflammation ◽

10.1155/2018/3275025 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8

Author(s):

Sinan Lin ◽

Ying Wang ◽

Li Li ◽

Peng Chen ◽

Ren Mao ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Serum Levels ◽

Chinese Patients ◽

Care Needs ◽

Roc Curve Analysis ◽

New Model

Background. The association between vitamin D3 and activity of Crohn’s disease (CD) is unclear in Chinese patients. In this study, we aimed to evaluate the correlations between serum levels of 25-hydroxyvitamin D3 (25(OH)D3) and disease activity and predict active disease based on vitamin D status. Methods. Between January 2014 and December 2017, 346 CD patients from the First Affiliated Hospital of Sun Yat-sen University were recruited and categorized into a group with 25(OH)D3 ≤ 20 ng/ml and a group with 25(OH)D3 > 20 ng/ml. The clinical characteristics, medication, and health-care needs were compared between the groups. The correlations among 25(OH)D3 and routine serum biomarkers and disease activity were examined. The predictive efficiency of 25(OH)D3 and other biomarkers for active diseases was also explored using receiver-operating characteristic (ROC) curve analysis. A new predictive model, −5∗25OHD3+2∗Hb+ESR, and a nomogram were established using Logistic Regression. Results. Patients with 25(OH)D3 ≤ 20 ng/ml had higher serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and platelets (PLT) and lower levels of hemoglobin (Hb) and albumin (ALB). Serum levels of 25(OH)D3 were inversely correlated with the score of Crohn’s Disease Activity Index (CDAI) (rs=−0.608). ROC analysis showed a better predictive value of −25(OH)D3 and the new model with areas under curve (AUC) of 0.804 and 0.879, respectively, than those of CRP (0.693) and ESR (0.713) in disease activity. A nomogram for prediction was established with a c-index of 0.882. Conclusions. Serum levels of 25(OH)D3 negatively correlated with CD activity in Chinese patients. The new model and a nomogram based on 25(OH)D3 showed a better efficiency in predicting disease activity in CD patients but warrants further study.

Download Full-text