Could potentially calprotectin be a promising biomarker to oracle biologic therapy response in rheumatoid arthritis?

Background The advent of novel biologic agents for the treatment of rheumatoid arthritis (RA) has proven to be highly productive. Nonetheless, high cost, side effects, and unresponsiveness to these agents dictates the assignment of biomarkers that can foretell treatment response. Currently, calprotectin (a member of the S100 protein family) is amongst the enormously studied candidates in this perspective. Yet, conflicting results have been published. The main purpose of this study was to explore the role of serum concentration of calprotectin to predict the response to biological therapy in RA patients, so as to customize RA treatment. Results Baseline serum calprotectin levels were significantly higher in RA patients compared to the control subjects (P value < 0.001). After receiving biologic therapy, a remarkable reduction (P < 0.001) in serum calprotectin was noted in RA cohort. Moreover, no correlation was found between the 28 joint count disease activity score (DAS28) and serum calprotectin levels neither before or after biologics. Intriguingly, no statistically significant association was detected between circulating calprotectin level and response to biological therapy. Conclusion Serum calprotectin concentrations could not be used as a biomarker to forecast clinical response to biological therapy in RA patients. However, further studies involving larger cohort of RA patients should be carried out to deliver more insight in this regard.

Small intestinal bacterial overgrowth in Alzheimer’s disease

The results of animal studies and clinical data support the gut microbiota contribution to the pathogenesis of Alzheimer’s disease (AD). The aim of this pilot study was to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO) and fecal markers of intestinal inflammation and permeability in AD patients. The study was conducted in 45 AD patients and 27 controls. Data on comorbidities, pharmacotherapy, and gastrointestinal symptoms were acquired from medical records and a questionnaire. SIBO was evaluated using lactulose hydrogen breath test. Fecal calprotectin and zonulin levels were assessed by ELISA assays. The positive result of SIBO breath test was found in 49% of the AD patients and 22% of the controls (p = 0.025). The comparative analysis between SIBO-positive and SIBO-negative AD patients with respect to the degree of cognitive impairment, comorbidities and used medications did not reveal any statistically significant difference, except for less common heartburn in SIBO-positive AD patients than in SIBO-negative ones (9 vs 35%, p = 0.038). The median fecal calprotectin and zonulin levels in the AD group compared to the control group amounted to 43.1 vs 64.2 µg/g (p = 0.846) and 73.5 vs 49.0 ng/ml (p = 0.177), respectively. In the AD patients there was no association between the presence of SIBO and fecal calprotectin level. Patients with AD are characterized by higher prevalence of SIBO not associated with increased fecal calprotectin level that may be related to anti-inflammatory effect of cholinergic drugs used in the treatment of AD.

Is Fecal Calprotectin an Applicable Biomarker of Gut Immune System Activation in Chronic Inflammatory Demyelinating Polyneuropathy? – A Pilot Study

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a complex autoimmune disease caused by dysregulated response to not fully recognized antigens. Some association between CIDP and inflammatory bowel disease (IBD) has been reported, but the exact pathophysiological links of these disorders are not well understood.Aim of the Study: To evaluate fecal calprotectin as a biomarker of gut inflammation in CIDP patients without IBD.Methods: Fifteen patients with CIDP and 15 healthy controls were included in the study. The CIDP diagnosis was based on the EFNS/PNS criteria. The occurrence of bowel symptoms was assessed based on a questionnaire. The quantitative evaluation of fecal calprotectin level was performed by the ELISA test.Results: The fecal calprotectin level (μg/g) expressed as median along with the lower and upper quartiles [25Q–75Q] was significantly higher in CIDP patients compared to the controls: 26.6 [17.5–109.0] vs 15.6 [7.1–24.1], p = 0.0066. Abnormal fecal calprotectin level (&gt;50 μg/g) was found in 33% of all CIDP patients and in none of the control subjects. The patients with abnormal fecal calprotectin level did not differ from the rest of the study group regarding the neurological status. The most common bowel symptoms reported by CIDP patients included constipation (33%), feeling of incomplete evacuation (33%), bloating (27%), and alternating bowel movement pattern (27%).Conclusion: In one-third of CIDP patients the signs of gut immune system activation have been observed. This finding may be associated with CIDP pathogenesis and induction of autoimmune response as well as concomitant dysautonomia with gastrointestinal symptoms.

Predictors of Surgical Intervention in Patients with Inflammatory Bowel Disease

Background Inflammatory bowel disease (IBD) is comprised of two major disorders: Ulcerative Colitis and Crohn’s disease. Ulcerative Colitis affects the colon, where as Crohn’s disease can involve any component of the gastrointestinal tract from the mouth to the perianal area. These disorders have somewhat different pathologic and clinical characteristics, but with substantial overlap; their pathogenesis remains poorly understood. Objective To determine & detect different predictors that help us to characterize patients with high probability of undergoing surgical intervention for inflammatory bowel diseases. Patients and Methods The present study was designed to detect & identify possible factors that can be used to predict surgical intervention in patients with IBD. The present study was a case control study that was conducted on 80 patients with inflammatory bowel disease (either controlled by medical treatment or needed surgical intervention as a part of disease control) who were recruited form Ain-Shams university hospitals and El Quabbary general hospital in Alexandria. In the present study, the mean age of the included patients was 36.67 ±8.5 years old and 50% of the patients were males. The mean age at the onset of the disease was 25.81 ±6.8 years old. Results In the present study, there were statistically significant differences between surgical and medical patients in terms of CDAI for CD (p &lt; 0.001) and Mayo score for UC (p &lt; 0.001). Surgical patients were more likely to have higher scores. CDAI and Mayo score were negative predictors of surgical treatment. CDAI score &gt; 287 and Mayo score &gt; 8.5 achieved high sensitivity and specificity for the detection of surgical treatment. In the present study, we found that there was statistically significant differences between surgical and medical patients in terms of Stool Calprotectin level. Surgical patients were more likely to have higher Stool Calprotectin level. Stool Calprotectin level was negative predictor of surgical treatment at a level of &gt; 341.5 microgm/gm with high sensitivity and specificity. Conclusion Surgical treatment is a common outcome in IBD. Certain clinical features and the extent of disease are risk factors for surgical intervention. Our study indicates that smoking, Chron’s disease, perianal disease, granulomas, higher severity scores, higher stool Calprotectin level, CRP, and ESR were associated with higher risks of surgical intervention. In addition, smoking, peri-anal disease, CDAI, Mayo score, Stool Calprotectin level, and CRP level were predictors of surgical treatment. The findings of our analysis have implications for practice, particularly in the promotion of preoperative individualized risk prediction. The ability to predict which patients will need surgery and target more intensive, early treatment to that group would be invaluable. Further research through large prospective cohort studies is needed to confirm our findings and conclusions.

Assessment of Calprotectin in blood and tissue of Acne Vulgaris patients of different clinical severities

Background Acne vulgaris is a multifactorial inflammatory skin disease of the pilosebaceous unit with complex pathogenesis. Calprotectin is a heterodimer of two calcium-binding proteins S100A8 and S100A9, which are members of the S100 protein family, and which play a role in various inflammatory processes, it is mainly present in the cytoplasm of neutrophils and expressed on the membrane of monocytes. Objective to assess the level of Calprotectin in blood and in tissue of AV patients and compare it with healthy controls. Beside correlate it with the degrees of severity of acne in order to further understand the role of Calprotectin in the pathogenesis of AV. Subjects and Methods This case-control study included 28 subjects who have AV, divided into four groups according to Global Acne Grading System: the first group included 7 patients with mild acne, the second group included 7 patients with moderate acne, the third group included 7 patients with severe acne, and the fourth group included 7 patients with very severe AV. In addition to a control group which included 28 apparently healthy individuals of matched age, sex and with no previous history of acne or active acne. All the patients were recruited from the outpatient clinic of Al Haud Al Marsoud hospital from September 2019 till January 2020. After taking the approval of research ethics committee (FMASU M S 22/2019) all subjects gave an informed consent to participate in this work. Results Our study showed that the increase in AV severity was not affected by the difference in gender, type of acne, nor disease duration. However, there was a significant correlation between plasma calprotectin level and AV severity. In addition to, There was a significant statistical correlation between the increase in the age of patients and the decrease in the severity of acne, which indicates that AV is more severe in younger patients than older ones. The correlation between the Plasma Calprotectin level in patients group and Tissue Calprotectin level in inflammatory lesions (papules) was non-significant. However, the correlation between the Plasma Calprotectin level in patients’ group and Tissue Calprotectin level in non-inflammatory lesions (comedones) was highly significant. Conclusion Plasma Calprotectin level showed significant relation with AV severity and presence of scar. The correlation between plasma Calprotectin level and tissue Calprotectin level in noninflammatory lesions (comedones) was highly significant.

Trends in Faecal Calprotectin Levels During Pregnancy in Non-IBD Patients

Background and Aims: No optimal marker exists to assess activity of inflammatory bowel disease (IBD) during pregnancy, though faecal calprotectin (FCP) is the most commonly used test. However minimal data exists on what a normal calprotectin level is during pregnancy and post-partum in healthy individuals. Objective: Our aim is to determine normal FCP levels during pregnancy and post-partum in a healthy population. Methods: We performed a prospective analysis of FCP levels from pregnant women at 16- and 34-weeks’ gestation and 4- and 12-weeks post-partum. Patient demographics were collected. FCP concentrations were measured with a quantitative ELISA assay. Results: 98 patients were included in our study. 172 maternal stool samples were collected in total; 62 samples at 16-weeks’ gestation, 48 samples at 34-weeks’ gestation, 38 samples from 4-weeks post-partum and 24 samples from 12-weeks post-partum. Median age was 33.0 years. 41 patients had a BMI > 25 (41.8%). 16 patients were ex-smokers (16.3 %). The median FCP levels at 16-weeks’ gestation was 29.5 µg/g (range 10–476 µg/g), median level from 34-weeks’ gestation was 25.6 µg/g (range 10–259 µg/g), from 4-weeks post-partum was 23.4 µg/g (range 10–318 µg/g) and 12-weeks post-partum was 29.4 µg/g (range 10–216 µg/g). There was no significant change in median FCP levels over the course of pregnancy and post-partum (p = 0.294). Conclusion: Faecal calprotectin levels are not affected by physiological changes in pregnancy or post-partum in normal healthy individuals without IBD. This suggests FCP is a useful tool for identifying flares of colitis during pregnancy.

Gut microbiota restoration through fecal microbiota transplantation: a new atopic dermatitis therapy

The pathogenesis of atopic dermatitis (AD) involves complex factors, including gut microbiota and immune modulation, which remain poorly understood. The aim of this study was to restore gut microbiota via fecal microbiota transplantation (FMT) to ameliorate AD in mice. FMT was performed using stool from donor mice. The gut microbiota was characterized via 16S rRNA sequencing and analyzed using Quantitative Insights into Microbial Ecology 2 with the DADA2 plugin. Gut metabolite levels were determined by measuring fecal short-chain fatty acid (SCFA) contents. AD-induced allergic responses were evaluated by analyzing blood parameters (IgE levels and eosinophil percentage, eosinophil count, basophil percentage, and monocyte percentage), the levels of Th1 and Th2 cytokines, dermatitis score, and the number of mast cells in the ileum and skin tissues. Calprotectin level was measured to assess gut inflammation after FMT. FMT resulted in the restoration of gut microbiota to the donor state and increases in the levels of SCFAs as gut metabolites. In addition, FMT restored the Th1/Th2 balance, modulated Tregs through gut microbiota, and reduced IgE levels and the numbers of mast cells, eosinophils, and basophils. FMT is associated with restoration of gut microbiota and immunologic balance (Th1/Th2) along with suppression of AD-induced allergic responses and is thus a potential new therapy for AD.

AB0571 RELATIONSHIP BETWEEN SERUM CALPROTECTIN LEVEL AND PRESENCE OF SUBCLINICAL ATHEROSCLEROSIS AND ARTERIAL STIFFNESS IN PATIENT WITH PSORIATIC ARTHRITIS

Background:Calprotectin is a member of S100 leukocyte. Serum calprotectin is a sensitive biomarker of disease activity in patients with psoriatic arthritis (PsA). While various CV risk score only shown modest correlation with augmented CV risk in patient with PsA, whether calprotectin could play an addition role remains uncertain.Objectives:To elucidate the association between serum calprotectin and subclinical atherosclerosis and arterial stiffness in patient with PsAMethods:Seventy-eight PsA patient (age: 53±11 years, 47(54%) male) without CV event was recruited into this cross-sectional study. High resolution carotid ultrasound was performed to assess the presence of carotid plaque and intima-media thickness (IMT). Arterial stiffness was measured by branchial-ankle pulse wave velocity (PWV) and augmentation index (AIx). Serum calprotectin level was measured by QUANTA Lite Calprotectin Extended Range ELISA kit from (INOVA Diagnostics, San Diego, CA, USA).Results:29/78 (38%) of patient had carotid plaque (CP+). Subject in CP+ group were of older age and higher inflammatory burden in terms of higher number of swollen joint and longer disease duration. The use of statins were also higher in CP+ group. Serum calprotectin level were significantly higher in CP+ group (639.2ng/ml ±378.2 in CP- group vs 911.8ng/ml ±429.4 in CP+ group, p=0.005) (Figure 1). Using multivariate logistic regression analysis, higher level of ln calprotectin were significantly associated with presence of carotid plaque (OR: 3.25, 95%CI: 1.22 to 8.69, p=0.019) after adjusting for baseline covariates. There was also significant correlation between calprotectin level and C-Reactive Protein (CRP) (r=0.237, p=0.037), mean IMT (r=0.301, p=0.021) and maximum IMT (r=0.265, p=0.043). However, no significant association were observed between calprotectin level and PWV or AIx.Figure 1.Conclusion:Increased calprotectin level were associated with presence of plaque and increased IMT. Serum calprotectin may be a novel biomarker for assessing CV risk in patient with PsA.Table 1.Multivariate analysis for factors associated with presence of carotid plaque.OR95% CIpDisease duration (years)1.101.02 to 1.190.018Ln Calprotectin3.251.22 to 8.690.019*Factors included in the multivariate analysis: age, gender, disease duration, swollen joint count, hyperlipidemia, Framingham 10-year CVD risk >10%, current use of statins, and calprotectin levelDisclosure of Interests:Isaac T. Cheng: None declared., Martin Li: None declared., Edmund K. Li: None declared., Alex Pui Wai Lee: None declared., Lai-Shan Tam Grant/research support from: Grants from Norvatis, Pfizer.