Evaluation Of Disease Activity Research Articles

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome

BackgroundILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. MethodsClinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. ResultsA total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). ConclusionAPCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS.

New Score Models for Assessing Disease Activity in Crohn's Disease Based on Bowel Ultrasound and Biomarkers: Ideal Surrogates for Endoscopy or Imaging.

Disease activity evaluation is important in Crohn's disease (CD). We aimed to establish new disease activity indices for CD based on noninvasive parameters. The data of 110 CD patients were retrospectively analyzed. Parameters from bowel ultrasound and biomarkers were measured to select the variables included in the models by univariate analysis. Logistic regression analysis was performed to predict mucosal and transmural activities defined by ileocolonoscopy or computed tomography enterography (CTE), respectively. The models' performance was measured by the area under the receiver operating characteristic (ROC) curve (AUC). Leave-one-out cross validation (LOOCV) was applied to adjust for overconfidence in the newly established score models. To predict mucosal activity, erythrocyte sedimentation rate (ESR) and (LimG × BWT)-SUM (the sum of the product of Limberg grade [LimG] and bowel wall thickness [BWT] of each bowel segment) were selected for Model A, and the equation was A=2 × ESR + 9.3 × (LimG × BWT)-SUM. The AUC of ROC, sensitivity, and specificity were 0.927, 89.8%, and 86.4%, respectively. The AUC of the ROC curve verified by LOOCV was 0.913. To predict transmural activity, albumin (ALB) and LimG-SUM (the sum of the LimG of all the bowel segments) were selected for Model B, which was established as B=-1.3 × ALB + 1.7 × LimG-SUM. The AUC of ROC, sensitivity, and specificity were 0.851, 78.0%, and 84.2%, respectively. The AUC of the ROC curve verified by LOOCV was 0.833. Nomograms were developed for two score models. New score models based on noninvasive parameters established in this study showed good abilities in detecting active disease and performed well in the validation phase.

BAFFR expression in circulating T follicular helper (CD4+CXCR5+PD-1+) and T peripheral helper (CD4+CXCR5-PD-1+) cells in systemic lupus erythematosus.

Circulating T follicular helper (cTfh) and T peripheral helper (Tph) subpopulations are shown to be higher in systemic lupus erythematosus (SLE) patients and have been involved in promoting extrafollicular B cell responses. However, a possible association with the B cell activating factor (BAFF), a cytokine mainly related to B cell responses and disease activity in SLE, has not been investigated. Therefore, this study aimed to evaluate the association of cTfh and Tph subpopulations with the BAFF system expression and clinical activity in SLE patients. This study included 43 SLE patients and 12 healthy subjects (HS). The identification of cTfh (CD4+CXCR5+PD-1+), Tph (CD4+CXCR5-PD-1+) cells, expression of membrane-bound BAFF (mBAFF), BAFFR, TACI, BCMA, and intracellular IL-21 was performed by flow cytometry. Serum levels of IL-21, CXCL13, and BAFF were analyzed using ELISA. The SLEDAI-2K score was used to evaluate disease activity in SLE patients. Compared with HS, SLE patients showed a significantly increased percentage of cTfh and Tph cells, higher in patients with clearly active disease. SLE patients had markedly higher IL-21-producing cTfh and Tph cells than HS. Both subpopulations were positively correlated with the disease activity in SLE patients. Tph cells were negatively correlated with CD19+CXCR5+ B cells and positively correlated with CD19+CXCR5- B cells. A low expression of mBAFF and their receptors TACI and BCMA was found on cTfh and Tph cells in SLE patients and HS. However, SLE patients with clearly active disease showed decreased expression of BAFFR on cTfh and Tph subpopulations than patients with mildly active/nonactive disease. Serum IL-21, CXCL13, and BAFF levels were higher in SLE patients than in HS. Levels of CXCL13 were correlated with disease activity. Non-significant correlations were observed among T cell subpopulations and IL-21, CXCL13, and BAFF levels. This study emphasizes the importance of cTfh and Tph cells in SLE pathogenesis. Besides the importance of IL-21, our results suggest that BAFFR could play a role in cTfh and Tph subpopulations in the autoimmunity context.

Eosinophilic Esophagitis Histologic Scoring System: Correlation with Histologic, Endoscopic, and Symptomatic Disease and Clinical Use.

The eosinophilic esophagitis histologic scoring system (EoEHSS) was developed to enhance the diagnostic standard of peak eosinophil count (PEC) in evaluating disease activity in EoE. (1) Correlate the EoEHSS and PEC to measures of symptomatic and endoscopic disease activity, (2) Correlate EoEHSS grade and stage subcomponents to clinical, radiology, and endoscopic markers of fibrotic disease, (3) Evaluate EoEHSS remission in asymptomatic patients with PEC < 15 eosinophils per high powered field (eos/hpf). Secondary analysis of prospective cohort data of 22 patients with EoE that underwent dietary therapy and endoscopy at 3 time points. Active disease was defined by EoEHSS grade or stage > 0.125, symptomatic disease by EoE symptom activity index > 20, endoscopic disease by endoscopic reference score > 2, and histologic disease by PEC ≥ 15 eos/hpf. EoEHSS remission was defined by esophageal inflammation (EI) grade of 0-1, EI stage of 0, total grade ≤ 3, and total stage ≤ 3. EoEHSS grade and stage did not correlate with symptomatic disease but did with endoscopic and histologic disease. PEC showed similar correlation pattern. Abnormal grade and stage had strong sensitivity (87-100%) but poor specificity (11-36%) to detect symptomatic, endoscopic, and histologic disease activity. Lamina propria fibrosis was evaluated in 36% of biopsies and did not correlate with minimum esophageal diameter. Out of 14 patients who were in complete symptomatic, endoscopic, and histologic remission, 8 met criteria for EoEHSS remission. The positive and negative correlations of EoEHSS to specific measures of symptomatic, histologic, and endoscopic activity suggest that it provides complementary information in EoE.

The Effect of Adherence to Mediterranean Diet on Disease Activity in Patients with Inflammatory Bowel Disease.

Mediterranean diet, owing to its infla mmati on-mo dulat ory effects, is considered a beneficial dietary regimen for patients with inflammatory bowel disease. Despite promising results in the literature, studies on this subject are still limited. Therefore, the aim of this study was to evaluate adherence to the Mediterranean diet in patients with inflammatory bowel disease and examine its impact on disease activity and quality of life. A total of 83 patients were included in the study. Mediterranean Diet Adherence Scale was used to evaluate adherence to the Mediterranean diet. Crohn's Disease Activity Index was used to evaluate disease activity in Crohn's disease. Disease activity was determined by using the Mayo Clinic score for ulcerative colitis. Quality of Life Scale Short Form-36 was used to evaluate the quality of life of patients. When the median Mediterranean Diet Adherence Scale score was 7 (1-12), only 18 patients (21.7%) showed strong adherence to the Mediterranean diet. Disease activity scores of patients with ulcerative colitis having low adherence to the Mediterranean diet were found to be higher (P < .05). In addition, some quality of life parameters were relatively higher in patients with ulcerative colitis who showed strong adherence to the Mediterranean diet (P < .05). For Crohn's disease, no significant difference was found in disease activity and quality of life with respect to adherence to the Mediterranean diet (P > .05). Stronger adherence to the Mediterranean diet in patients with ulcerative colitis can help improve quality of life and modulate disease activity. However, further prospective studies are needed to investigate the potential use of the Mediterranean diet in inflammatory bowel disease management.

Multi-b-values-fitting readout-segmentation of long variable echo-trains diffusion-weighted imaging (RESOLVE DWI) in evaluation of disease activity and curative effect of axial spondyloarthritis (axSpA).

Disease activity is relevant to the treatment and prognosis of axSpA, and methods to quantitatively assess disease activity and efficacy of axSpA are still being explored. The purpose of this study was to find an optimal quantitative indicator for evaluating disease activity and curative effect of axSpA, using multi-b-values-fitting RESOLVE DWI. The prospective study included 106 patients divided into axSpA group (n=89) and no-axSpA group (n=17) by Assessment of Spondyloarthritis international Society (ASAS) criteria. The axSpA group were divided into active group and inactive group according to ASDAS-CRP. The active group treated with systematic tumour necrosis factor inhibitors (TNFi) was selected as treatment group (n=20). All patients underwent MRI examination of sacroiliac joints (SIJs), including RESOLVE DWI. The ADC values of subchondral bone marrow in SIJs were measured (ADC50,500 was b=50,500s/mm2 fitting, ADC50,700 was b=50,700s/mm2 fitting, and ADC50,500,700 was b=50,500,700s/mm2 fitting). By comparing the ADC values between different groups, a relatively optimal b-values-fitting sequence was obtained, further evaluating curative effect of the treatment group. The ADC values of axSpA group, inactive group and active group SIJs were all higher than those of no-axSpA group. The ADC values of active group SIJs were all higher than those of inactive group. ADC50,500,700 had the largest AUC, relative higher sensitivity and specificity while taking account of the image quality than ADC50,700 and ADC50,500 between different groups. In the treatment group, there was no significant difference in ADC values between pre-treatment and 3 weeks, 3 weeks and 6 weeks, 6 weeks and 12 weeks (all P>0.0083, Bonferroni-corrected threshold), while the decreased ADC values in the interval of 6 weeks or more were statistically significant (all P<0.0083, Bonferroni-corrected threshold). Multi-b-values-fitting (b=50,500,700s/mm2) RESOLVE DWI has a certain advantage in evaluating disease activity of axSpA. It was worth noting that short-term review (3 weeks or less) of RESOLVE DWI was unsatisfactory and review at 6 weeks or later would help to evaluate curative effect of axSpA.

Value of tumor necrosis factor-alpha and high-sensitive cardiac troponin-I as early predictors of subclinical atherosclerosis and their relation to disease activity in patients with rheumatoid arthritis: A case-control study

Patients with rheumatoid arthritis (RA) have a higher risk of cardiovascular disease (CVD) compared to the general population, which leads to increased morbidity and mortality. Inflammation is the key in RA and CVD. Our study aimed to refine cardiovascular (CV) risk assessment in RA patients by using carotid intima-media thickness (cIMT) as a marker of subclinical atherosclerosis. We also explored whether proinflammatory cytokines represented by tumor necrosis factor-alpha (TNF-α) and high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, could be correlated in RA patients. The study included 80 RA patients and 80 control subjects. TNF-α and hs-cTnI levels were measured. Subclinical atherosclerosis was evaluated by cIMT by means of carotid ultrasound. Disease activity score 28 (DAS28) was used to evaluate disease activity. hs-cTnI and TNF-α serum levels were higher in RA patients compared to controls (p=0.001). There was a significant difference in the median of cIMT between cases and controls (median (IQR) 0.9 (0.2) for cases, 0.7 (0.1) for controls, (p=0.001). A significant correlation was found between the level of TNF-α and hs-cTnI (p=0.002). Also, there was a significant correlation between the cIMT level and TNF-α and hs-cTnI (p=0.003 and p=0.002, respectively). Significant correlation was found between cIMT, TNF-α, and hs-cTnI in relation to the DAS28 score (p&lt;0.001, p&lt;0.001, and p=0.001, respectively). In conclusion, patients with RA are more likely to develop subclinical atherosclerosis, as reflected in increased cIMT. Higher levels of hs-cTnI in RA patients may correlate with the presence of occult cardiovascular disease. TNF-α and hs-cTnI correlations can reveal the interplay between disease activity and CVD. Thus, inflammation must be the primary target of various therapeutic approaches.

Investigation of the effect of oral selenium on the reduction of clinical symptoms and joint pain in patients with rheumatoid arthritis in the Iranian population.

Rheumatoid arthritis (RA) is a common inflammatory joint disease. Since inflammation and nitrosative stress play an important role in the pathogenesis of RA, drugs that have antioxidant and anti-inflammatory effects can be effective as adjuvant treatment in these patients. Selenium is a compound that has been shown in recent studies to have anti-inflammatory and antioxidant effects. Therefore, the aim of this study was to investigate the effect of oral selenium on the reduction of clinical symptoms and joint pain in patients with RA. Fifty one patients with moderate and severe RA were randomly divided into selenium and placebo groups. The first group of patients received century Selenium drug at a dose of 200 micrograms twice a day for 12 weeks along with standard RA interventions and treatments, and the second group received standard treatments of RA along with a placebo. Clinical symptoms were evaluated with standard indicators to evaluate disease activity before and after the intervention in the 12th week. Examination of clinical symptoms at the end of the study showed that in the selenium group and after 12 weeks, a reduction in clinical symptoms and joint pain were observed, which was statistically significant compared to before the study began. Meanwhile, no significant changes were observed in the patients of the placebo group in terms of reducing symptoms and joint pains. A dose of 200 micrograms of oral selenium twice a day for 12 weeks can significantly reduce clinical symptoms and joint pain in patients with RA. This article is protected by copyright. All rights reserved.

Relationship between galectin-3 level and disease activity in ankylosing spondylitis patients

Background and aimsAnkylosing spondylitis (AS) is a chronic inflammatory disease that chiefly affects the sacroiliac joints and the spine. Galectin-3, a chimera-type member of the galectin family, binds glycoconjugates containing N-acetyllactosamine. Galectins play a role in regulation of embryogenesis, angiogenesis, neurogenesis, and immunity. The aim of the present study was to evaluate the serum galectin-3 level and its possible association with disease activity in AS patients. Forty five AS patients and 35 healthy controls enrolled in this study. All participants with a history of hyperlipidemia, liver, renal, hematological, familial thyroid, neoplastic, autoimmune infectious diseases and using anti-inflammatory drugs were excluded from the study. Serum galectin-3 levels concentration was measured using a commercial chemiluminescent microparticle immunoassay. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score–CRP (ASDAS-CRP) were used to evaluate disease activity in AS patients.ResultsSerum galectin-3 levels were significantly higher in AS patients compared to the control group (p = 0.04). A correlation was determined between the serum galectin-3 levels and BASDAI and ASDAS-CRP scores in the AS patients (r = 0.49, p < 0.001; r = 0.56, p < 0.001, respectively). In AS patients, serum galectin-3 levels were significantly related with CRP levels but were not related with ESR (r = 0.57, p < 0.001; r = 0.25, p = 0.09, respectively).ConclusionsThe serum galectin-3 levels were higher in AS patients and were correlated with disease activity. This study may be useful to reveal the role of galectin-3 in inflammation and to evaluate disease activity in AS patients.

Explore the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab in patients with ulcerative colitis

Objectives: To analyze the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab (VDZ) in patients with ulcerative colitis (UC). Methods: Retrospective study. By retrieving the clinical database of the Second Affiliated Hospital of Wenzhou Medical University, the patients with moderately to severely active UC were collected, who underwent VDZ treatment from January 2020 to June 2022. The modified Mayo score and Mayo endoscopic score (MES) were employed to evaluate disease activity and intestinal inflammation in UC patients, respectively. According to whether vitamin D was supplemented during VDZ treatment, the patients were divided into supplementary group and non-supplementary group. According to baseline serum 25(OH) D level, UC patients were divided into vitamin D deficiency group and non-deficiency group. According to whether vitamin D was supplemented, the patients of each group were divided into supplementary subgroup and non-supplementary subgroup, respectively. The clinical response rate, clinical remission rate and mucosal healing rate at week 30 after receiving VDZ treatment and the retention rate of VDZ at the 72nd week were observed. The effect of baseline serum 25 (OH) D level on the efficacy of vitamin D supplementation was analyzed by chi-square test. The effects of vitamin D supplementation on the clinical efficacy and drug retention of VDZ in UC were analyzed by chi-square test and Kaplan-Meier curve, respectively. Results: A total of 80 patients with moderately to severely active UC, who were aged (39.4±13.0) years(18-75 years), 37 male and 43 female, were included. There were 43 cases in supplementary group and 37 cases in non-supplementary group. There were 59 cases in the deficiency group, including 32 cases in the supplementary subgroup and 27 cases in the non-supplementary subgroup. There were 21 cases in the non-deficiency group, including 11 cases in the supplementary subgroup and 10 cases in the non-supplementary subgroup. At week 30, the average level of serum 25(OH) D was shown to be higher in supplementary group than that at week 0 [(24.5±5.4) vs (17.7±6.7) μg/L, P<0.001]. At week 30, in contrast with non-supplementary group, erythrocyte sedimentation rate(ESR)[75.0% (24.3%, 86.7%) vs 32.7% (-2.6%, 59.3%), P=0.005] and modified Mayo score [(4.7±2.8) vs (2.3±2.7) points, P<0.001] and MES score [(1.2±1.1) vs (0.4±0.9) points, P=0.001] were significantly reduced, clinical response rate [79.1%(34/43) vs 56.8%(21/37), P=0.032], clinical remission rate [67.4%(29/43) vs 29.7%(11/37), P=0.001] and mucosal healing rate [72.1%(31/43) vs 37.8%(14/37), P=0.002] were higher. At week 72, drug retention rate of VDZ was shown to be higher in supplementary group than in non-supplementary group [55.8%(24/43) vs 27.0%(10/37), P=0.004]. The further analysis showed that vitamin D supplementation could only improve clinical response rate[71.9%(23/32) vs 44.4%(12/27), P=0.033], clinical remission rate[62.5%(20/32) vs 14.8%(4/27), P<0.001], mucosal healing rate[68.8%(22/32) vs 22.2%(6/27), P<0.001] and drug retention rate [53.1%(17/32) vs 13.8%(4/27), P=0.001] in the patients with vitamin D deficiency. Conclusion: Vitamin D supplementation contributes to improving clinical response rate, clinical remission rate, mucosal healing rate and drug retention rate of VDZ in UC patients.

The Role of Interleukin-22 in The Diagnosis and Evaluation of Disease Activity in Rheumatoid Arthritis

Background: Rheumatoid Arthritis (RA) is a chronic autoimmune disease that primarily affects small joints, resulting in joint inflammation, pain, and limited mobility. The identification of novel biomarkers specific to RA could enhance early diagnosis and treatment and also improve the monitoring of the disease activity and treatment response. In this study, the levels of IL-22 were measured in 133 patients with inflammatory arthritis using the ELISA method with the aim of assessing the diagnostic value of IL-22 in the diagnosis of RA and evaluating the disease activity. The findings revealed that serum IL-22 levels were significantly higher in RA patients compared to patients with other types of inflammatory arthritis. Additionally, positive correlations were observed between IL-22 and disease activity scores as determined by CDAI, DAS-28 ESR, and DAS-28 CRP. Notably, when IL-22 was used as a diagnostic tool, with a cut-off value of ≥ 26.9 pg/ml, it exhibited a sensitivity of 83%, specificity of 75%, and an AUC of 0.838. Furthermore, significant associations were found between IL-22 levels and the age of RA patients, while no significant correlations were observed with gender, BMI, and smoking index. It is noteworthy that IL-22 levels were significantly correlated with ESR, RF titer, and ACPA levels. Consequently, IL-22 can be regarded as a valuable biomarker for diagnosing RA and evaluating disease activity. Subjects and method: This cross-sectional study was conducted from September 2022 to January 2023, involving 133 patients with inflammatory arthritis, including RA and other forms of inflammatory arthritis. All patients were recruited from As-Sader Teaching Hospital in Najaf. The ages of the patients included in the present study range from 20 to 70 years, with a sample comprising 116 females and 17 males. Results: The higher median (IQR) value of IL-22 was observed among the RA patients [36.9 (28.6-63.7) pg/ml] compared to that of the other patients with inflammatory arthritis [23.6 (19.8-26.8) pg/ml]. The difference between the two groups of patients was highly significant (P &lt; 0.0001). Among the RA patients, a highly significant difference in the median (IQR) level of IL-22 was observed among the disease activity groups according to CDAI, DAS-28 ESR, and DAS-28 CRP (P &lt; 0.0001). Conclusion: Interleukin-22 can be regarded as a reliable biomarker for the diagnosis of RA and holds potential for assessing disease activity.

#4006 ADDING 6-MONTH PARAMETERS FOR THE PREDICTION OF RENAL PROGNOSIS IN ANCA-ASSOCIATED GLOMERULONEPHRITIS

Abstract Background and Aims Antineutrophil-cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) with kidney involvement (AAV-GN) frequently evolves to end-stage kidney disease (ESKD) despite aggressive immunosuppressive treatment. Several risk scores have been used to assess renal prognosis. We aimed to determine whether kidney function and markers of AAV-GN activity after 6 months could improve the prediction of ESKD. Method This retrospective and observational study included adult patients with AAV-GN recruited from 6 French nephrology centers (including from the Maine-Anjou AAV registry). The primary outcome was kidney survival. Analyses were conducted in the whole population and in a sub-population that did not develop ESKD early in the course of the disease. Results 241 patients were included in the whole cohort, with a median follow-up of 59 months. At diagnosis, Berden classification and Renal Risk Score (RRS) were not found better than kidney function (eGFR) alone, at predicting ESKD (C-index = 0.70, 0.79, 0.82, respectively). At 6 months, 20 patients reached ESKD. In the sub-population of 221 patients, 6 months eGFR outperformed Berden classification and RRS (C-index = 0.88, 0.62, 0.69, respectively) to predict ESKD. RRS performed better when it was updated with the eGFR at 6 months instead of the baseline eGFR. While 6-months proteinuria was associated with ESKD and improved ESKD prediction, hematuria and serological remission did not. Conclusion This work suggests the interest of the reassessment of the renal prognosis 6 months after AAV-GN diagnosis. Kidney function at this time remains the most reliable for predicting renal outcome. To improve the long-term prediction of ESKD, there may be a place for repeated kidney biopsy following induction treatment, in order to obtain a precise evaluation of disease activity, discuss the immunosuppressive treatment strategy and improve prognosis scores.

#5260 PLASMA AND URINE METABOLOMIC PROFILES REVEAL POTENTIAL BIOMARKERS AND PROVIDE VALUABLE INSIGHTS INTO THE MECHANISMS OF MPO-ANCA-GN

Abstract Background and Aims Currently, the precise mechanism of myeloperoxidase- anti-neutrophil cytoplasmic antibody associated glomerulonephritis (MPO-ANCA-GN) remains elusive. And there is a lack of dependable biomarkers for evaluating disease activity, therapeutic resistance, and risk of relapse. We try to seek valuable biomarkers and explore the mechanism of MPO-ANCA-GN by metabolomics. Method Urine and plasma samples from 63 MPO-ANCA-GN, 31 lupus nephritis (LN), 15 IgA nephropathy (IgAN), and 15 minimal change disease (MCD) patients and 30 HC were collected for metabolomics analysis. The samples were analyzed using Ultra Performance Liquid Chromatography (UPLC) and Tandem mass spectrometry (MS/MS). The different groups of samples were compared using Partial Least Squares-Discriminant Analysis. A Receiver Operator Characteristic (ROC) curve was constructed to assess the performance of the metabolite model in identifying active renal vasculitis. KEGG annotation and enrichment analysis were performed for key pathways. Results All metabolites in urine and plasma samples including hydrophilic compounds and hydrophobic compounds were identified. Compared with the disease control (DC) and HC, we observed 79 significantly upregulated metabolites (VIP&amp;gt;1, FDR&amp;lt;0.05, FC&amp;gt;1.5) and 32 downregulated metabolites (VIP&amp;gt;1, FDR &amp;lt;0.05, FC&amp;lt;0.67) in the plasma samples of MPO-ANCA-GN patients. KEGG enrichment analysis suggested that these upregulated metabolites were mainly associated with phenylalanine metabolism and galactose metabolism and downregulated metabolites were mainly associated with bile secretion, steroid biosynthesis, and ovarian steroidogenesis. Compared with the DC and HC, we identified a total of 122 differential metabolites in the urine samples of MPO-ANCA-GN patients, 40 of which were significantly upregulated (VIP&amp;gt;1, FDR&amp;lt;0.05, FC&amp;gt;1.5) and 68 of which significantly were downregulated (VIP&amp;gt;1, FDR &amp;lt;0.05, FC&amp;lt;0.67). Subsequently, KEGG analysis revealed that these upregulated metabolites were mainly enriched in glycerolipid metabolism, lipid and atherosclerosis, cholesterol metabolism, insulin resistance, regulation of lipolysis in adipocytes, vitamin digestion and absorption, fat digestion and absorption (Corrected P &amp;lt; 0.05). Downregulated metabolites were mainly enriched in steroid hormone biosynthesis (Corrected P &amp;lt; 0.05). Nine MPO-ANCA-GN patients with paired plasma and six MPO-ANCA-GN patients with paired urine during the active and remission phase were included in the study. A total of 504 differential metabolites in plasma samples were identified between the active and remission phase based on VIP value &amp;gt;1, P &amp;lt; 0.05, and FC &amp;gt;1.5 or FC &amp;lt; 0.6. Of these, 425 metabolites were downregulated, while 79 lipid metabolites were upregulated in the active group. MPO-ANCA-GN patients were divided into two groups according to Mayo Clinic/Renal Pathology Society Chronicity Score: Minimal-mild group and Moderate-severe group. In plasma samples, our data showed that 3-Methoxysalicylic Acid, Carnitine C20:5, and isoxanthopterin presented good ability in distinguishing between the minimal-mild group and the moderate-severe group, with an AUC &amp;gt; 0.7. In urine samples, cyclohexylamine and arachidonic acid (AUC &amp;gt; 0.8) can distinguish the two groups well. Conclusion We identified many novel potential metabolic biomarkers in urine and plasma samples for evaluating disease activity, therapeutic resistance, and risk of relapse in patients with MPO-ANCA-GN.

Role of abbreviated non-contrast-enhanced MR-enterography in the evaluation of Crohn's disease activity and complications as an alternative for full protocol contrast-enhanced study: A systematic review and meta-analysis.

Crohn's disease (CD) is a chronic disorder that often starts at a young age and involves periods of remission and relapse. Prompt diagnosis of relapses through screening is crucial due to the potential morbid complications of untreated active inflammation. Magnetic resonance enterography (MRE) is a noninvasive technique to screen for active inflammation. The standard protocol involves intravenous injection of contrast agents with potential side effects. Some abbreviated non-contrast-enhanced MRE protocols are proposed as alternatives for conventional MRE to identify active inflammation. Currently, there is controversy regarding the applicability and accuracy of these protocols. This study aims to describe and compare these protocols and evaluate their accuracy in detecting active inflammation and CD complications. Results from a systematic search of three databases in August 2022 were queried and screened by abstract and full text. Eligible studies were qualitatively and quantitatively analyzed by diagnostic test accuracy meta-analysis. 59 studies entered the systematic review, and 37 were eligible for meta-analysis. Diffusion-weighted imaging (DWI) and fast T2-weighted (T2w) sequences were most frequently used in abbreviated protocols and showed non-inferior accuracy compared to the full protocol in detecting active inflammation. ADC and qualitative DWI had pooled sensitivity of 90% (CI: 82-95%) and 89% (CI:82-93%) and pooled specificity of 94% (CI: 88-97%) and 89% (CI: 79-94%), respectively for detecting active inflammation. Moreover, T2w and combined T2w+DWI sequences had pooled sensitivity of 80% (CI: 64-90%) and 76% (CI: 61-86%) and pooled specificity of 90% (CI: 80-95%) and 87% (CI: 74 - 94%), respectively. Unenhanced protocols show relatively poor diagnostic accuracy in detecting penetrating complications of CD. Magnetization transfer imaging (MTI) has demonstrated excellent accuracy in detecting fibrosis. High heterogeneity was observed in all subgroups, and accuracy was reported to be highly operator dependent in most studies. An abbreviated protocol consisting of DWI and fast T2w imaging can potentially replace the full protocol MRE. Full protocol MRE will still have its role in identifying penetrating complications. MTI should be indicated in case of suspected fibrostenotic disease.

Dipeptidyl peptidase 4 as a potential serum biomarker for disease activity and treatment response in rheumatoid arthritis.

The treatment of rheumatoid arthritis (RA) related to the disease activity. However, the lack of highly sensitive and simplified markers limits the evaluation of disease activity. We sought to explore potential biomarkers associated with disease activity and treatment response in RA. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis was performed to determine the differentially expressed proteins (DEPs) in serum collected from RA patients with moderate or high disease activity (determined by DAS28) before and after 24weeks of treatment. Bioinformatic analysis were performed for DEPs and hub proteins. In the validation cohort, 15 RA patients were enrolled. Key proteins were validated by enzyme-linked immunosorbent assay (Elisa), correlation analysis and ROC curve. We identified 77 DEPs. The DEPs enriched in humoral immune response, blood microparticle, and serine-type peptidase activity. KEGG enrichment analysis displayed that the DEPs were significantly enriched in cholesterol metabolism and complement and coagulation cascades. Activated CD4+T cell, T follicular helper cell, natural killer cell, and plasmacytoid dendritic cell significantly increased after treatment. Fifteen hub proteins were screened out. Among them, dipeptidyl peptidase 4 (DPP4) was the most significant protein associated with clinical indicators and immune cells. Serum concentration of DPP4 was testified to significantly increase after treatment and inversely correlate with disease activity indicators (ESR, CRP, DAS28-ESR, DAS28-CRP, CDAI, SDAI). Significant reduction was found in the serum CXC chemokine ligand10 (CXC10) and CXC chemokine receptor 3 (CXCR3) after treatment. Overall, our results suggest that serum DPP4 might be a potential biomarker for disease activity assessment and treatment response of RA.

Clinical value of fecal calprotectin for evaluating disease activity in patients with Crohn's disease.

Objective: To explore the clinical value of fecal calprotectin (FC) for evaluating disease activity in patients with Crohn's disease (CD) and its relationship with disease location. Methods: Patients with CD were enrolled retrospectively, and clinical data, including FC levels, were collected. Clinical activity was assessed using the Crohn's disease activity index (CDAI). Endoscopic activity was assessed using a simple endoscopic score for Crohn's disease (SES-CD). The partial SES-CD (pSES-CD) was scored for the size of ulcers in each segment as defined by the SES-CD and was calculated as the sum of segmental ulcer scores. Results: This study included 273 CD patients. The FC level was significantly positively correlated with the CDAI and SES-CD, with correlation coefficients of 0.666 and 0.674, respectively. The median FC levels in patients with clinical remission and mildly active and moderately-severely active disease were 41.01, 164.20, and 444.45μg/g. These values were 26.94, 66.77, and 327.22μg/g during endoscopic remission and mildly and moderately-severely active stages, respectively. Compared with c-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and other biomarker parameters, FC was better at predicting disease activity for CD patients. For an FC <74.52μg/g, the area under the curve (AUC) for predicting clinical remission was 0.86, with a sensitivity of 89.47% and a specificity of 71.70%. Moreover, endoscopic remission was predicted with a sensitivity of 68.02% and a specificity of 85.53%. The AUC was 0.83, and the cutoff value was 80.84μg/g. In patients with ileal and (ileo) colonic CD, FC was significantly correlated with the CDAI, SES-CD, and pSES-CD. The correlation coefficients were 0.711 (CDAI), 0.473 (SES-CD), and 0.369 (pSES-CD) in patients with ileal CD and 0.687, 0.745, and 0.714 in patients with (ileo) colonic CD, respectively. For patients in remission, those in the active stage, and those with large or very large ulcers, differences in FC levels were not significant between patients with ileal and (ileo) colonic CD. Conclusion: FC is a reliable predictor of disease activity in patients with CD, including those with ileal CD. FC is thus recommended for the routine follow-up of patients with CD.

Magnetic resonance imaging for evaluation of bowel inflammation and disease activity in Crohn's disease: A systematic review and meta-analysis

The aim of this systematic review and meta-analysis was to determine the performance of magnetic resonance imaging (MRI) in the diagnosis of bowel inflammation and disease activity in Crohn's disease (CD). MEDLINE, Embase and Web of Science databases of biomedical literature were systematically searched to identify studies that investigated the diagnostic accuracy of MRI in diagnosing bowel inflammation and disease activity in CD by comparing it with reference standards. Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality. The summary sensitivity and specificity were estimated using the bivariate model, and hierarchical summary receiver operating characteristic (HSROC) parameters were calculated and plotted. Of 5492 citations of interest, 34 articles contained the diagnostic accuracy data. Of these, results for the small bowel and the colorectum were reported separately in 19 studies and jointly by 21 studies. The meta-analytic summary sensitivity and specificity under the bivariate model were 90.9% (95% CI, 85.8%–94.2%) and 90.2% (95% CI, 81.9%–95.0%), respectively. The sensitivities and specificities of individual studies ranged from 55% to 100% and 51% to 100%, respectively. Substantial heterogeneity was observed in both sensitivity (I2 = 84.9%) and specificity (I2 = 78.8%). The HSROC curve also showed considerable heterogeneity between studies. Although the meta-analytic summary accuracy of MRI was high for the diagnosis of bowel inflammation in CD, the summary estimates might be unreliable due to the presence of high heterogeneity. El objetivo de esta revisión sistemática y metaanálisis fue determinar el rendimiento de la resonancia magnética nuclear (RM) en el diagnóstico de la inflamación intestinal y la actividad de la enfermedad en la enfermedad de Crohn (EC). Se realizaron búsquedas sistemáticas en las bases de datos de literatura biomédica de MEDLINE, Embase y Web of Science para identificar estudios que investigaran la precisión diagnóstica de la RM en el diagnóstico de la inflamación intestinal y la actividad de la enfermedad en la EC comparándola con estándares de referencia. Evaluación de la calidad de los estudios de precisión diagnóstica: se utilizó la herramienta 2 para evaluar la calidad del estudio. La sensibilidad y la especificidad resumidas se estimaron mediante el modelo bivariado, y se calcularon y trazaron los parámetros de características operativas del receptor resumidas jerárquicas (HSROC). De 5.492 citas de interés, 34 artículos contenían datos de precisión diagnóstica. De estos, los resultados para el intestino delgado y el colorrectal se informaron por separado en 19 estudios y en forma conjunta en 21 estudios. La sensibilidad y la especificidad del resumen metanalítico bajo el modelo bivariado fueron del 90,9% (IC del 95%, 85,8%-94,2%) y el 90,2% (IC del 95%, 81,9%-95,0%), respectivamente. Las sensibilidades y especificidades de los estudios individuales variaron del 55 al 100% y del 51 al 100%, respectivamente. Se observó heterogeneidad sustancial tanto en la sensibilidad (I2 = 84,9%) como en la especificidad (I2 = 78,8%). La curva HSROC también mostró una considerable heterogeneidad entre los estudios. Aunque la precisión del resumen metaanalítico de la RM fue alta para el diagnóstico de inflamación intestinal en la EC, las estimaciones del resumen pueden no ser confiables debido a la presencia de una gran heterogeneidad.

Correlation of serum adenosine deaminase activity with disease activity in patients with primary Sjögren's syndrome

BackgroundPrimary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease primarily affecting the exocrine glands, which has a variety of clinical manifestations and unclear pathogenic mechanisms. Adenosine deaminase (ADA) is an enzyme involved in the breakdown of purines, and changes in its activity have been associated with a number of autoimmune diseases. This study aims to investigate the relationship between serum ADA activity and disease activity in patients with pSS. MethodsIn this study, 196 patients with pSS and 196 healthy controls were enrolled. Serum ADA activity and clinical laboratory parameters were collected and analyzed in both groups. Pearson correlation analysis was used to examine the correlation between ADA activity and clinical laboratory parameters, as well as the correlation between ADA activity and the disease activity score. ResultsCompared with healthy controls, the activity of ADA in the serum of pSS patients was significantly increased (P < 0.0001), and the ADA activity was significantly decreased after immunosuppressive treatment (P < 0.0001). Correlation analysis revealed that the activity of ADA was significantly positively correlated with erythrocyte sedimentation rate (ESR) (r = 0.3, P < 0.0001) and serum immunoglobulin G (IgG) levels (r = 0.5, P < 0.0001), and significantly negatively correlated with high-density lipoprotein (HDL) (r = −0.4, P < 0.0001). Furthermore, there was a significant positive correlation between ADA activity and the disease activity score as measured by the Sjögren's Syndrome Disease Activity Index (SSDAI) (r = 0.4, P < 0.0001). ConclusionThis study found that patients with pSS have higher activity of ADA in serum, which is associated with disease activity as measured by SSDAI. These results suggest that ADA activity may be a potential biomarker for evaluating disease activity and treatment efficacy in pSS patients. Additionally, ADA may be a potential target for the treatment of pSS patients.

An Interim Analysis of Efficacy and Safety Data in Black and Hispanic Patients With Multiple Sclerosis Receiving Ocrelizumab Treatment in the CHIMES Trial (S31.006)

An Interim Analysis of Efficacy and Safety Data in Black and Hispanic Patients With Multiple Sclerosis Receiving Ocrelizumab Treatment in the CHIMES Trial (S31.006)

P173 Evaluating disease activity in established psoriatic arthritis with ultrasound

Abstract Background/Aims Early diagnosis, tight disease activity control and a treat-to-target approach are now recognised as critical factors that improve the outcome of patients with psoriatic arthritis (PsA). The traditional method used to assess disease activity is clinical examination (CE) by counting the number of tender and swollen joints. Ultrasound (US) has proven its superiority over CE for assessing the presence of synovitis in some studies. We aimed to identify the frequency and location of subclinical synovitis in a cohort of PsA patients with established disease. Methods Patients with established PsA were recruited. All gave informed, written consent and local ethical approval was obtained. All patients had a standard CE including 68/66 tender/swollen joint count. Grayscale (GS) and power doppler (PD) US of a standard set of 44 joints was performed using a GE logiq-P9 machine utilising 6-15-MHz and 8-18-MHz linear transducers. GS and PD were scored on a 0-3 semiquantitative scale for each joint. The presence of US active joints was defined as a GS-score ≥2 and/or PD-score ≥1. Results 78 patients were enrolled; 46/78 were female with a median age = 61 years (range 41-80). Median duration of PsA disease = 31.5 years (range 41-80), 40/78 were on bDMARDs and 27/78 on csDMARDs. The median TJC = 2 (range of 0-6) and mean CRP = 3.2 (SD 3.5). The most common sites for subclinical synovitis were wrists, knees, and metatarsophalangeal joints (see Table 1). 36 patients (46.2%) achieved a clinical state of minimal disease activity (MDA). 11 patients in MDA (30.5%) had a PD-score of &amp;gt; 1, suggesting they did not achieve minimal ultrasound disease activity (MUDA). Conclusion These data demonstrate that a proportion of established PsA patients deemed to have MDA actually have sonographic evidence of active disease. A previous study showed that PD-synovitis in PsA patients in clinical remission was a strong predictor of disease flare. It is unclear if subclinical synovitis in PsA is linked to radiographic progression. Combining CE and sonographic evaluation is an attractive approach to identifying subclinical disease. However, a validated ultrasound composite index, which includes the key joint areas frequently affected in PsA, is needed. Disclosure S. Sundanum: None. H. Darcy: None. P. Gallagher: None. F. Young: None. L. O'Neill: None. D. Veale: None.