Serum Galectin-3 as a Non-Invasive Marker for Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these patients and 18 controls. Serum and urinary galectin-3 levels in IBD patients were comparable to those in controls. Among IBD patients, those with high fecal calprotectin, indicating severe disease, exhibited lower serum and elevated urinary galectin-3 levels compared to those with low calprotectin levels. Serum galectin-3 levels were inversely correlated with C-reactive protein levels. PSC patients displayed higher serum and urinary galectin-3 levels than IBD patients, with the highest serum levels observed in PSC patients with coexisting IBD. There was no correlation between serum and urinary galectin-3 levels and laboratory indicators of liver injury in both IBD and PSC patients. In conclusion, this study demonstrates that serum and urinary galectin-3 levels can distinguish IBD from PSC patients, and also reveals higher serum galectin-3 levels in PSC-IBD patients compared to those with isolated PSC.

Establishing a pediatric reference interval for plasma calprotectin.

Plasma calprotectin is a promising new biomarker of inflammatory activity and has been found to correlate well with clinical and endoscopic activity in children and adolescents with inflammatory bowel disease. A pediatric reference interval for plasma calprotectin has not been established for the Phadia 250 EliA™ Calprotectin fluoroenzyme immunoassay. In studies regarding pre-analytical properties, excellent precision and stability was found. However, sensitivity to hemolysis was demonstrated. We identified pediatric blood samples from apparently healthy children who were referred by their general practitioner for blood sampling including measurement of hemoglobin (Hb) and C-reactive protein (CRP). We excluded samples from children who had undergone additional blood sampling within 2 months before or after the index sample, if Hb was outside of local reference ranges or CRP levels were above the lower limit of the measuring interval (LLM), and any samples with a hemolysis above 0.02 mmol/L. Using this algorithm, we identified 141 blood samples. No outliers were identified. We established the following reference intervals according to CLSI C28-A3 using non-parametric statistics: 1-17 years: 16-246 µg/L. Our results may prove useful for further utilization of plasma calprotectin as a marker of inflammation in children and adolescents with inflammatory disorders.

Serum biomarkers and their relationship to axial spondyloarthritis associated with inflammatory bowel diseases.

Spondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.

The Role of Serum Calprotectin in Defining Disease Outcomes in Non-Systemic Juvenile Idiopathic Arthritis: A Pilot Study.

Serum calprotectin (MRP8/14) is currently being studied as a promising biomarker of disease activity and outcome in patients with juvenile idiopathic arthritis (JIA) but the data in the literature are conflicting. The aim of our study was to investigate the potential role of serum calprotectin as biomarker of disease activity and flare/remission in a group of nsJIA patients during a follow-up period of 18 months. In this prospective longitudinal study, two groups of patients with ns-JIA (55 active patients and 56 patients in remission according to Wallace's criteria) and a control group (50 children) were recruited at baseline from January 2020 to September 2021. JIA patients were followed for up to 18 months at four timepoints: 3 months (T1), 6 months (T2), 12 months (T3) and 18 months (T4). At each timepoint, the following were recorded: JADAS27, blood counts, ESR, CRP, albumin, ferritin and serum calprotectin. To illustrate the performance of calprotectin, Kaplan-Meier curves were constructed from baseline to relapse/remission, dichotomizing patients at baseline in positive/negative on the basis progressive calprotectin cut-offs. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates. Comparing baseline clinical and laboratory data of the three groups (active vs. inactive JIA vs. controls), only serum calprotectin reached statistical significance (active patients vs. inactive (p = 0.0016) and vs. controls (p = 0.0012)). In the inactive group, during the 18 months of follow up, 31 patients (55.3%) had a relapse. Comparing the baseline data of relapsers vs. non-relapsers, serum calprotectin showed higher levels (p = 0.001) in relapsers. In survival analysis, a log rank test showed significant differences of up to 12 ng/mL (p = 0.045). Multivariate Cox regression confirmed that only baseline calprotectin levels were independently associated with disease recurrence. In the active group, in the 12 months of follow-up, 19 patients (38%) entered remission of the disease. In addition, in this group, the only statistical difference at the baseline was the value of MPR8/14 (p = 0.0001). Log rank test showed significant differences up to 10 ng/mL (p = 0.003). In the multivariate Cox regression, serum calprotectin levels at baseline were independently associated with remission. In conclusion, our study would suggest a dual role for calprotectin in predicting future relapse and treatment response in patients with nsJIA, thus influencing therapeutic decisions and management of these patients during follow up.

Serum Calprotectin - a NET Product - as a Biomarker of Disease Activity in Patients with Systemic Lupus Erythematosus: A Single-Center Case-Control Study from Poland.

BACKGROUND Calprotectin (S100A8/A9 or myeloid-related protein 8/14) is a heterodimeric S100 complex expressed in leukocytes. Calprotectin participates in development of the inflammatory response by binding to receptors for advanced glycation end-products (RAGE) and Toll-like receptors (TLR). The clinical activity of systemic lupus erythematosus (SLE) is evaluated using the Systemic Lupus International Collaborating Clinics (SLICC) criteria and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This Polish single-center case-control study aimed to evaluate serum levels of calprotectin as a rapid diagnostic biomarker of SLE (59 patients with SLE were compared with 52 healthy controls). MATERIAL AND METHODS Calprotectin concentration was measured with the use of enzyme-linked immunosorbent assay (ELISA). The SLE activity of the patients was assessed by the SLEDAI scale. Statistical analysis of the results was carried out using MedCalc 15.8 software. P<0.05 was considered statistically significant. RESULTS A significantly higher concentration of calprotectin was found in the study group compared to the control group (medians: 3.11 vs 2.45 ng/ml; P=0.0013). We found that calprotectin has high sensitivity (89.83%) and specificity (53.85%) in differentiating between SLE patients and healthy volunteers. We found that calprotectin has very high sensitivity (100%) and specificity (82.46%) in detection of patients with moderate and severe SLE assessed using SLEDAI. CONCLUSIONS Consistent with previous studies, serum calprotectin level was revealed to have potential as a rapid diagnostic biomarker of disease activity in patients with SLE.

Dynamics of circulating calprotectin accurately predict the outcome of moderate COVID-19 patients.

BACKGROUND: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated. METHODS: We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death. FINDINGS: After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19. INTERPRETATION: These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit. FUNDING: The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.

Effect of Ramadan intermittent fasting on inflammatory markers, disease severity, depression, and quality of life in patients with inflammatory bowel diseases: A prospective cohort study.

BACKGROUND: Intermittent fasting (IF) during the month of Ramadan is part of the religious rituals of Muslims. The effect of intermittent fasting on disease activity in inflammatory bowel diseases (IBD) is still unknown. This is the first study to assess the effect of IF during Ramadan on inflammatory markers in patients diagnosed with IBD. The effects on clinical disease activity, quality of life, and levels of depression were also assessed. METHODS: Patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) who intended to observe Ramadan fasting were recruited. The following were assessed immediately before and at the end of Ramadan: Serum CRP and stool calprotectin, partial Mayo score, Harvey Bradshaw index (HBI), Simple IBD questionnaire (SIBDQ), and Hamilton depression scale questionnaire. RESULTS: 80 patients diagnosed with IBD were recruited (60 UC, 20 CD). Serum CRP and stool calprotectin did not show a significant change before vs after fasting (median CRP 0.53 vs 0.50, P value = 0.27, Calprotectin 163 vs 218 respectively, P value = 0.62). The partial Mayo score showed a significant rise after fasting (median 1 before vs 1 after fasting, mean: 1.79 vs 2.33 respectively, P value = 0.02). Harvey-Bradshaw index did not show a significant change after fasting (median 4 vs 5, P value = 0.4). Multiple linear regression revealed that older age and a higher baseline calprotectin were associated with a higher change in Mayo score after fasting (P value = 0.02 and P value = 0.01, respectively). No significant change was detected in SIBDQ or Hamilton depression scale scores. CONCLUSIONS: In patients diagnosed with UC, IF during Ramadan was associated with worsening of clinical parameters, the effect was more pronounced in older patients and those with higher baseline calprotectin levels. However, IF during Ramadan was not associated with an adverse effect on objective inflammatory markers (CRP and calprotectin).

Can fecal calprotectin reflect your colonic status?

Background: Organic colonic manifestation may be difficult to be differentiated from functional one. Inflammatory bowel disease (IBD) is a common chronic inflammatory and destructive disease of the bowel wall. Chronic inflammation is associated with ulcerations, strictures, perforations, and it is a risk factor for dysplasia and cancer. To reduce these long-standing complications, IBD patients are in a continuous need for early diagnosis1. Markers, such as erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP), fecal calprotectin (FC) have been widely used as noninvasive parameters for IBD monitoring. We aimed, in this current study, to evaluate the value of fecal calprotectin and other noninvasive biomarkers in predicting abnormal histologic findings in patients undergoing colonoscopy.in addition to determine the cutoff value which predict IBD2. Methods: The present prospective study included 160 patients with complaint of colicky abdominal pain with frequent diarrhea associated with mucous and infrequent bleeding per rectum for more than 6 months. They presented partial improvement with medication and recurrence once stopping the treatment These patients had been recently diagnosed with IBD at many primary healthcare centers covering the areas of the Kafrelsheikh and Zagazik governorate in the North of Egyptian Nile delta. After complete history, clinical examination, and laboratory investigation, they were referred to the IBD clinic at Kafrelsheikh University Hospital for assessment and ileocolonoscopy with biopsies. Results: There was a wide spectrum of age of the studied patients, with mean age 40.12±7.88 (minimum 18 and maximum 56 years). Regarding gender, males represented 87.5% of the studied patients. Forty percent of the patients with colonic manifestation were smokers, 57% preferred a spicy diet, and the majority had low educational level (77.5%). Forty percent had obvious blood in stool, 55% had occult blood, and raised ESR CRP occurred in 32.5% and 50%, respectively. Fecal calprotectin cutoff was>159, with sensitivity 92.8% and specificity 97.5%. Conclusions: Biomarkers (FC, ESR, CRP) can be used as noninvasive parameters for the early diagnosis and prediction of organic colonic disease. Fecal calprotectin in the IBD group revealed significant area under the curve (AUC) values and cutoff> 159, with sensitivity 92.8% and specificity 97.5%. (AU)

Evaluation of serum calprotectin as novel biomarker in psoriatic patients: a prospective pilot study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease characterized by erythematous plaques that can extend along the entire skin surface. In the latest years, it has been shown that serum calprotectin correlated strongly with several inflammatory biomarkers. Since high levels of calprotectin have been found in psoriatic lesions, it is of paramount importance to investigate the role of serum calprotectin as a possible novel diagnostic marker of psoriasis. Aim of our prospective pilot study was to assess the level of serum calprotectin in psoriatic patients. METHODS: Between January 2018 and July 2019, 45 subjects were enrolled at the Dermatology Unit of Magna Graecia University of Catanzaro, Italy. Thirty-two of them were psoriatic patients and 13 healthy controls. Psoriasis severity was assessed by the Psoriasis Area Severity Index. RESULTS: A statistically significant difference between the two groups (P=0.01) was found in terms of body mass index, higher among patients than in controls. By performing the Student's t-test for unpaired data, serum calprotectin resulted significantly higher (P=0.033) among psoriatic patients than in controls. Furthermore, performing the receiver operator characteristic curve analysis, serum calprotectin showed a significant area under the curve, implying its possible role in finding psoriatic patients. Our study aimed to evaluate the serum levels of calprotectin in a group of psoriatic patients and in a control group. The results showed that serum calprotectin levels were significantly higher in the patient group than in the control group. This result confirms the observations present in the literature. CONCLUSIONS: In this pilot study psoriatic patients had a significant high level of serum calprotectin than healthy subjects, and this biomarker had high accuracy in identifying patients. Further studies, with larger sample size will need to confirm our data.

Diagnostic accuracy of calprotectin in periprosthetic joint infection: a diagnostic meta-analysis.

BACKGROUND: Periprosthetic joint infection (PJI) is considered to be one of the most challenging complications of joint replacement, which remains unpredictable. As a simple and emerging biomarker, calprotectin (CLP) has been considered to be useful in ruling out PJI in recent years. The purpose of this study was to investigate the accuracy and sensitivity of CLP in the diagnosis of PJI. METHODS: We searched and screened the publications from PubMed, Web of Science, EMBASE, and Cochrane Library from database establishment to June 2021. Subsequently, Stata version 16.0 software was used to combine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), operating characteristic curve, and area under the curve (AUC). Heterogeneity across articles was evaluated by the I2 statistics. Finally, sources of heterogeneity were detected by subgroup analysis based on study design, detection method, sample size, and cutoff values. RESULTS: A total of 7 studies were included in our study, comprising 525 patients. The pooled sensitivity, specificity, PLR, and NLR of CLP for PJI diagnosis were 0.94(95% CI 0.87-0.98), 0.93(95% CI 0.87-0.96), 13.65(95% CI 6.89-27.08), and 0.06(95% CI 0.02-0.15), respectively, while the DOR and AUC were 222.33(95% CI 52.52-941.11) and 0.98 (95% CI 0.96-0.99), respectively. CONCLUSION: Synovial CLP is a reliable biomarker and can be used as a diagnostic criterion for PJI in the future. However, the uncertainty resulting from the poor study numbers and sample sizes limit our ability to definitely draw conclusions on the basis of our study.

Serum calprotectin as a novel biomarker for severity of COVID-19 disease.

BACKGROUND: Some biomarkers have been reported to be related to the prognosis of the coronavirus disease 2019 (COVID-19). There are sparse data regarding the prognostic value of serum calprotectin in COVID-19 patients. AIMS: This study aimed to investigate the relationship between serum calprotectin level and clinical severity of COVID-19 disease in hospitalized patients. METHODS: This retrospective cross-sectional cohort study included 80 consecutive hospitalized patients with confirmed diagnosis of COVID-19. The study population was divided into two groups as patients hospitalized in the intensive care unit (ICU) and patients hospitalized but not in the ICU. The serum calprotectin levels, other laboratory, and clinical parameters were compared between groups. RESULTS: The mean age of the patients was 66.5 ± 15.7 years. Of the patients, 42 were in the ICU and 38 were not. Serum calprotectin level and acute-phase reactants such as C-reactive protein, procalcitonin, ferritin, fibrinogen, and white blood cell were significantly higher in ICU patients than in non-ICU patients. ROC curve analysis identified that serum calprotectin level was a predictor for ICU requirement with an area under the curve of 0.641 (p = 0.031). Logistic regression analysis revealed that serum calprotectin was a significant determinant for whether or not patient required the ICU. CONCLUSIONS: These findings demonstrate that serum calprotectin level seems to be a useful biomarker that can predict the severity of COVID-19 disease. Serum calprotectin is a significant predictor of ICU requirement in patients with COVID-19.

Circulating levels of calprotectin, a signature of neutrophil activation in prediction of severe respiratory failure in COVID-19 patients: a multicenter, prospective study (CalCov study).

OBJECTIVE: Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients. METHODS: This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission. RESULTS: Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L; p < 0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L; p = 0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068). CONCLUSION: Serum calprotectin can be used as an early predictor of severity in COVID-19 patients.

Effectiveness of Crohn's Disease Exclusion Diet for Induction of Remission in Crohn's Disease Adult Patients.

Exclusive enteral nutrition (EEN) is a first-line treatment in active, mild to moderate Crohn's disease (CD) in children. The Crohn's disease exclusion diet (CDED), which avoids products known to have a pro-inflammatory effect on the intestinal mucosa, presents similar effectiveness to EEN for inducing remission in the paediatric population. The aim of the study was to evaluate the effectiveness of the CDED in inducing remission in adult patients. Between March 2020 and May 2021, 32 patients in a gastroenterology outpatient centre were treated according to the assumptions of the CDED. The patients were seen at baseline, at week 6, and at week 12 of the study. During the visits, anthropometric measurements and laboratory tests were performed, Crohn's disease activity index (CDAI) was calculated, and the Inflammatory Bowel Disease Questionnaire (IBDQ) was completed. The study included a total of 32 participants, 18 women (56.3%) and 14 men (43.7%). Clinical remission was obtained in 76.7% patients after 6 weeks and in 82.1% after 12 weeks of therapy. Calprotectin levels were significantly lower in the second follow-up compared with baseline (p = 0.021). The CDED is an effective therapy for inducing remission in the adult CD population.

Evaluation of Serum Calprotectin Levels in Patients with Inflammatory Bowel Disease.

BACKGROUND: Fecal calprotectin has been proposed as a useful biomarker of disease activity in inflammatory bowel disease (IBD). However, the role of calprotectin in systemic circulation is not well established. Thus, this study aimed to quantify serum calprotectin levels to identify a potential inflammatory marker for IBD. METHODS: Ninety-eight patients with ulcerative colitis (UC) and 105 patients with Crohn's disease (CD) were prospectively enrolled and clinically scored. Ninety-two healthy, age-matched subjects served as controls. Blood samples from UC and CD patients and controls were analyzed for serum calprotectin levels and routine laboratory parameters. Disease activity was assessed by partial Mayo score and Harvey-Bradshaw index for UC and CD, respectively. RESULTS: Serum calprotectin levels were higher in CD and UC patients than in controls and were higher during active disease than during inactive disease in CD but not in UC. In UC, serum calprotectin levels were correlated with C-reactive protein (CRP) but not with other laboratory parameters or disease activity. In CD, serum calprotectin levels were positively correlated with disease activity, serum CRP, and platelet count. In UC and CD, serum calprotectin and CRP levels increased during the acute phase and decreased towards remission. CONCLUSIONS: Serum calprotectin is an inflammatory marker in IBD but might be more effective in evaluating patients with CD than those with UC. Further studies are needed to confirm these findings and to better determine the specific uses of serum calprotectin in routine practice.

Assessment of antiphospholipid antibodies and calprotectin as biomarkers for discriminating mild from severe COVID-19.

BACKGROUND: To explore the association of thrombo-inflammatory biomarkers with severity in coronavirus disease (COVID-19), we measured antiphospholipid antibodies (aPL) and calprotectin in sera of COVID-19 patients. METHODS: Anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I antibodies were measured using enzyme-linked immunosorbent assay (ELISA) and multiplex flow immunoassay (MFIA) in hospitalized COVID-19 patients (N = 105) and healthy controls (N = 38). Anti-phosphatidylserine/prothrombin antibodies, calprotectin, and C-reactive protein (CRP) levels were also measured. We assessed the potential correlation between calprotectin levels and various laboratory parameters that were measured during the hospitalization period. After stratifying COVID-19 patients into two groups by their oxygenation status or acute respiratory distress syndrome presentation, the discriminatory performance of each biomarker was evaluated. RESULTS: A high proportion of COVID-19 patients (29.5%, 31/105) had low aCL IgM titers that were detectable by ELISA but mostly below the detection limit of MFIA. Calprotectin levels in severe groups of COVID-19 were significantly higher than those in non-severe groups, while CRP levels revealed no significant differences. Serum calprotectin levels showed strong to moderate degree of correlation with other routinely used parameters including peak levels of CRP, ferritin, procalcitonin, BUN, and neutrophil-to-lymphocyte ratio, but a negative correlation with minimal lymphocyte count and CD4+ T cells. The discriminatory performance was highest for calprotectin in discriminating severe groups of COVID-19. CONCLUSIONS: Serum calprotectin levels were significantly elevated in severe COVID-19 cases. The prevalence of clinically significant aPL did not differ. The link between calprotectin and inflammatory pathway in COVID-19 may help improve the management and outcomes of COVID-19 patients.

Plasma calprotectin in the emergency department: a potential clinical biomarker for patients with infectious diseases.

Increased levels of plasma calprotectin are reported in patients with infectious diseases. However, the clinical usefulness of calprotectin as a biomarker to identify patients with infectious diseases in the emergency department (ED) setting has not been investigated. To study the ability of calprotectin to discriminate patients with acute infectious diseases and dyspnea from patients with other causes of acute dyspnea in the ED setting. Patients aged ≥18 years seeking ED during daytime on weekdays between March 2013 and July 2018, with acute dyspnea, were included. Participants (n = 1287) were triaged according to Medical Emergency Triage and Treatment System-Adult score (METTS-A) or Rapid Emergency Triage and Treatment System (RETTS), and blood samples were collected. The association between calprotectin and other markers of infectious diseases, i.e. biomarkers (CRP, leucocytes) and body temperature, was studied. The predictive value of calprotectin for the outcome of acute infection was evaluated with receiver operating characteristic (ROC) analysis. Univariate cross-sectional regression showed significant associations between calprotectin and leucocytes, CRP and body temperature. Patients with severe infections including pneumonia (n = 119) had significantly higher concentrations of calprotectin compared to patients with heart failure (n = 162) or chronic obstructive pulmonary disease (n = 183). When tested for the outcome of acute infection (n = 109), the area under the ROC curve (AUROC) was for CRP 0.83 and for calprotectin 0.78. Plasma calprotectin identifies infectious diseases in ED patients with acute dyspnea, and the clinical usefulness of Calprotectin in the ED has to be further studied.

Serum Levels of Fibroblast Growth Factor 19 Correlate with the Severity of Diarrhea and Independently from Intestinal Inflammation in Patients with Inflammatory Bowel Disease or Microscopic Colitis.

BACKGROUND: In chronic diarrhea patients, massive over-reporting symptom-based criteria for functional bowel disorders are pitfalls. There is currently no objective biomarker that may provide a correct correlation with the severity of chronic diarrhea. To clarify the role of fibroblast growth factor-19 (FGF-19) as a biomarker of objective measurements of the severity of diarrhea in comparison with a patientreported outcome, based on the Bristol Stool Form (BSF) Scale. METHODS: Consecutive 100 patients with chronic diarrhea underwent standard investigations with laboratory tests, fecal calprotectin (FC), endoscopy with biopsies, and serum FGF-19. All patients and 14 healthy controls completed a diary recording, BSF, and stool frequency. RESULTS: We found that irritable bowel syndrome with diarrhea (IBS-D) n = 21/23 (91%) reported a high number on BSF ≥6, compared to patients with inflammatory bowel diseases (IBD) 56/77 (72%) with BSF ≥ 6 (P = .011). FGF-19 median serum levels were significantly lower in Microscopic colitis (0.010 pg/mL) and IBD patients (0.009 pg/mL) compare to IBS-D (266.9 pg/mL) and high levels in healthy subjects (463 pg/mL) (P < .001). Strong inverse correlation of FGF-19 with the stool frequency/day and stool index was found (r = -0.800, P < .001; r = -0.739, P < .001), independently from disease activity (r = -0.718, P = .001; r = -0.792, P = .001). CONCLUSION: Serum FGF-19 can become a new biomarker for evaluating the severity of diarrhea with objectively and independently from intestinal inflammation. FC and FGF-19 are predictive biomarkers for the organic cause of diarrhea.

A cross-sectional cohort study of the activity and turnover of neutrophil granulocytes in juvenile idiopathic arthritis.

BACKGROUND: The inflammatory process in juvenile idiopathic arthritis (JIA) involves both the innate and the adaptive immune system. The turnover and activity of neutrophil granulocytes may be reflected by proteins secreted from primary or secondary granules and from the cytoplasm of sequestered cells. Our primary aim was to compare the levels of the secondary neutrophil granule protein human neutrophil lipocalin (HNL), in JIA patients and controls, and to explore a possible priming of neutrophils through parallel analyses in plasma and serum. A secondary aim was to relate the levels of HNL to two other well-studied leukocyte proteins, S100A8/A9 and myeloperoxidase (MPO), as well as to clinical aspects of JIA. METHODS: The concentrations of the three biomarkers in serum, two of them also in plasma, were measured using enzyme-linked immunosorbent assay in 37 children with JIA without medical treatment, in high disease activity based on juvenile arthritis disease activity score 27 (JADAS27), 32 children on medical treatment, mainly in lower disease activity, and 16 healthy children. We assessed for differences between two groups using the Mann-Whitney U test, and used the Kruskal-Wallis test for multiple group comparisons. Spearman rank correlation, linear and multiple regression analyses were used for evaluation of associations between biomarker concentrations and clinical scores. RESULTS: The concentrations of HNL and MPO in serum were significantly increased in children with JIA (p < 0.001, p = 0.002) compared with healthy children, but we found no difference in the plasma levels of HNL and MPO between children with JIA and controls. The serum concentrations of MPO and HNL were unaffected by medical treatment, but S100A8/A9 was reduced by medical treatment and correlated with JADAS27 in both univariate (r = 0.58, p < 0.001) and multivariate (r = 0.59, p < 0.001) analyses. CONCLUSIONS: Neutrophil granulocytes in children with JIA are primed to release primary and secondary granule proteins, without relation to medical treatment, whereas signs of increased turnover and sequestration of neutrophil granulocytes are reduced by treatment. Levels of neutrophil-originating proteins in serum most likely reflect underlying disease activities of JIA.

Critical COVID-19 is associated with distinct leukocyte phenotypes and transcriptome patterns.

BACKGROUND: Prognostic markers for disease severity and identification of therapeutic targets in COVID-19 are urgently needed. We have studied innate and adaptive immunity on protein and transcriptomic level in COVID-19 patients with different disease severity at admission and longitudinally during hospitalization. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected at three time points from 31 patients included in the Norwegian SARS-CoV-2 cohort study and analysed by flow cytometry and RNA sequencing. Patients were grouped as either mild/moderate (n = 14), severe (n = 11) or critical (n = 6) disease in accordance with WHO guidelines and compared with patients with SARS-CoV-2-negative bacterial sepsis (n = 5) and healthy controls (n = 10). RESULTS: COVID-19 severity was characterized by decreased interleukin 7 receptor alpha chain (CD127) expression in naïve CD4 and CD8 T cells. Activation (CD25 and HLA-DR) and exhaustion (PD-1) markers on T cells were increased compared with controls, but comparable between COVID-19 severity groups. Non-classical monocytes and monocytic HLA-DR expression decreased whereas monocytic PD-L1 and CD142 expression increased with COVID-19 severity. RNA sequencing exhibited increased plasma B-cell activity in critical COVID-19 and yet predominantly reduced transcripts related to immune response pathways compared with milder disease. CONCLUSION: Critical COVID-19 seems to be characterized by an immune profile of activated and exhausted T cells and monocytes. This immune phenotype may influence the capacity to mount an efficient T-cell immune response. Plasma B-cell activity and calprotectin were higher in critical COVID-19 while most transcripts related to immune functions were reduced, in particular affecting B cells. The potential of these cells as therapeutic targets in COVID-19 should be further explored.