Useful Biomarker Of Disease Activity Research Articles

Role of Serum Progranulin as a Biological Marker in SLE Patients

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease caused by the disorders of immune regulation. In the past few years, increasing evidence has shown that progranulin (PGRN) is an immunomodulatory protein that is upregulated in SLE patients. Progranulinmay be involved in the pathogenesis of SLE, so, it might be a marker for disease activity. Objectives This work aimed to investigate the clinical significance of PGRN in patients with SLE regarding its role in pathogenesis and its relation to clinical manifestations and disease activity. Subjects and Methods This case-control study was conducted on 50 SLE patients classified according to the 2019 European League Against Rheumatism and the American College of Rheumatology (2019 EULAR/ACR), and were subdivided according to SLE Disease Activity Index-2000 (SLEDAI-2K) score into 25 patients with low disease activity (LDA) and 25 with high disease activity (HDA), in addition to 20 patients with autoimmune diseases other than SLE, and 20 healthy adults as a control group. We measured concentrations of serum PGRN with quantitative enzyme-linked immunosorbent assay (ELISA) in all studied participants. We assessed the correlation between the serum PGRN levels and different laboratory parameters, clinical symptoms and established disease-activity indices. Results Serum PGRN levels were significantly higher in SLE patients than healthy controls as well as when compared to the group of patients with autoimmune diseases other than SLE. They also significantly correlated with values of laboratory assays and clinical parameters such as ESR, 24 hours urine protein, SLEDAI-2kscore, and total damage scores; and inversely correlated with C3, C4 and Hb concentrations. Conclusion Serum PGRN could be a useful biomarker for disease activity of SLE.

Serum neurofilament light chain predicts spinal cord atrophy in neuromyelitis optica spectrum disorder

Levels of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) are useful biomarkers of disease activity and disability in neuromyelitis optica spectrum disorder (NMOSD). Here we investigated the association of sNfL and sGFAP levels with brain and spinal cord volumes in patients with NMOSD. Fifteen patients with NMOSD were enrolled in this prospective study. The median baseline level of sNfL was 42.2 (IQR, 16.1–72.6) pg/mL and decreased to 8.5 (IQR, 7.4–16.6) pg/mL at the end of the study. The reduction in sNfL was associated with a 7.5% loss of cervical spinal cord volume (CSCV) (p = 0.001). The levels of sGFAP reduced from 239.2 (IQR, 139.0–3393.3) pg/mL at baseline to 108.5 (IQR, 74.2–154.6) pg/mL. However, there was no strong correlation between sGFAP levels and CSCV changes during the follow-up period. Our data suggested that sNfL level is a useful biomarker for predicting spinal cord atrophy in patients with NMOSD.

In chronic spontaneous urticaria, IgE and C-reactive protein are linked to distinct microRNAs and interleukin-31.

Chronic spontaneous urticaria (CSU) is a common and disabling disease. Assessments of IgE and C-reactive protein (CRP) are recommended in the diagnostic work-up, but the role and clinical relevance of these biomarkers are not well characterized. Moreover, it remains unknown if elevated levels of IgE or CRP are linked to CSU microRNA (miRNA) signatures or interleukin 31 (IL-31). We measured IgE and CRP serum levels in 47 CSU patients (and 45 healthy controls) and determined CSU disease activity using the urticaria activity score (UAS7). Expression levels of miR-155 and miR-221 were assessed by RT-PCR, and IL-31 levels were determined by ELISA. Total IgE and CRP levels were independently increased in CSU patients. IgE and CRP levels were highest and lowest in patients with high and mild disease activity. IgE levels correlated with miR-155 levels, whereas CRP levels correlated with miR-221 levels. miR-155 and miR-221 were significantly overexpressed in CSU patients. ROC analyses linked miRNA-155 and CSU with a sensitivity of 79% and specificity of 87%, and miRNA-221 and CSU with a sensitivity of 75% and specificity of 91%. High CRP and miR-221 expression levels were linked to elevated levels of IgG anti-TPO and IL-31. IgE and CRP are useful biomarkers for disease activity in CSU, with distinct miRNA profiles. High CRP and miR-221 levels may point to autoimmune CSU and a role for IL-31.

Choriocapillaris Flow Deficit in Tubercular Serpiginous-Like Choroiditis with and without Paradoxical Worsening

ABSTRACT Purpose The aim is to analyze automated quantification of choriocapillaris flow deficit (CCFD) on swept-source (SS)-optical coherence tomography angiography (OCTA) in tubercular serpiginous-like choroiditis (TBSLC). Methods In this prospective study, automated CCFD calculations were performed on SS-OCTA and compared with CCFD areas on indocyanine green angiography (ICGA). Patients were divided into two groups based on the occurrence of paradoxical worsening (PW). Results Twenty-nine eyes (29 subjects; 18 males; mean age: 33±12 years) were included. The mean CCFD at baseline was 34.9 ± 4.3% on OCTA in eyes without PW and 35.4 ± 5.0% on SS-OCTA with PW (p = .77). At 4 and 12 weeks, CCFD on SS-OCTA improved to 30.6 ± 3.9% and 28.0 ± 4.2% (p < .001) without PW, respectively, and increased to 42.9 ± 4.4% and 48.8 ± 4.1% (p < .001) with PW, respectively. The SS-OCTA CCFD correlated well with ICGA (r = 0.48; p < .001). Conclusions Automated quantitative serial assessment of CCFD on SS-OCTA can serve as a useful biomarker of disease activity in eyes with TBSLC.

Artículo traducido] Asociación entre eosinófilos de sangre periférica y cutáneos con la gravedad del penfigoide ampolloso y los resultados terapéuticos

Background and aimsA dermal inflammatory infiltrate rich in eosinophils is a prominent histological feature of bullous pemphigoid (BP) and peripheral blood eosinophilia has been documented in 50–60% of BP patients. Nevertheless, the impact of circulating and dermal infiltrate eosinophil levels on BP remains poorly understood. The main objective of this work was to investigate the association of peripheral blood and dermal infiltrate eosinophil levels with clinical and immunological characteristics of the disease. Material and methodsRetrospective cohort study including all patients diagnosed with BP between 2011 and 2020. ResultsThe study cohort included 233 patients with BP. The mean baseline peripheral blood eosinophil count was 956.3 ± 408.6 × 106/L and the mean number of tissue eosinophils at the dermal hot spot area was 30.5 ± 19.0. Patients with disseminated presentation (i.e. BSA > 50%) had significantly higher peripheral blood eosinophil counts (P = .028). Mucosal involvement was significantly associated with lower dermal eosinophil count (P = .001). Requiring inpatient care and relapsing were significantly associated with high peripheral blood eosinophil count (P = .025; P = .020, respectively). Among the 68 patients who experienced a relapse, 31 had peripheral blood eosinophilia (i.e. > 500 × 106/L) at relapse (44.2%). Peripheral blood eosinophil counts at baseline and at relapse were significantly correlated (r = 0.82, P < .001). ConclusionsPeripheral blood and cutaneous eosinophils levels may be useful biomarkers for disease activity and treatment outcomes in BP. Monitoring peripheral blood eosinophil counts may allow early detection of relapse.

Association of Peripheral Blood and Cutaneous Eosinophils With Bullous Pemphigoid Disease Severity and Treatment Outcomes

Background and aimsA dermal inflammatory infiltrate rich in eosinophils is a prominent histological feature of bullous pemphigoid (BP) and peripheral blood eosinophilia has been documented in 50–60% of BP patients. Nevertheless, the impact of circulating and dermal infiltrate eosinophil levels on BP remains poorly understood. The main objective of this work was to investigate the association of peripheral blood and dermal infiltrate eosinophil levels with clinical and immunological characteristics of the disease. Material and methodsRetrospective cohort study including all patients diagnosed with BP between 2011 and 2020. ResultsThe study cohort included 233 patients with BP. The mean baseline peripheral blood eosinophil count was 956.3±408.6×106/L and the mean number of tissue eosinophils at the dermal hot spot area was 30.5±19.0. Patients with disseminated presentation (i.e. BSA>50%) had significantly higher peripheral blood eosinophil counts (P=0.028). Mucosal involvement was significantly associated with lower dermal eosinophil count (P=0.001). Requiring inpatient care and relapsing were significantly associated with high peripheral blood eosinophil count (P=0.025; P=0.020, respectively). Among the 68 patients who experienced a relapse, 31 had peripheral blood eosinophilia (i.e. >500×106/L) at relapse (44.2%). Peripheral blood eosinophil counts at baseline and at relapse were significantly correlated (r=0.82, P<0.001). ConclusionsPeripheral blood and cutaneous eosinophils levels may be useful biomarkers for disease activity and treatment outcomes in BP. Monitoring peripheral blood eosinophil counts may allow early detection of relapse.

P214 Plasma fatty acid binding protein 2, interleukin-10 and lipopolysaccharides as biomarkers for microscopic colitis

Abstract Background The pathogenesis of microscopic colitis (MC) is still poorly understood and there are no non-invasive diagnostic markers to aid in disease diagnosis. Fatty acid binding protein 2 (FABP2) is expressed in enterocytes and colonocytes (although to a lesser extent) and is released after intestinal injury. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is reduced in inflammatory bowel diseases. Lipopolysaccharides (LPS) are bacterial endotoxins that promote inflammation and their presence in systemic circulation represents impaired intestinal barrier function. Our aim was to investigate these compounds as possible non-invasive diagnostic biomarkers for MC and compare their profile between MC and ulcerative colitis (UC). Methods 63 patients with active MC, 52 healthy controls (HCs), 43 patients with active and 43 with inactive UC were recruited for the study. The presence of active disease was assessed using the Hjortswang criteria in MC and Mayo score in UC patients. Plasma concentrations of FABP2, IL-10 and LPS were measured using Human FABP2/I-FABP Quantikine ELISA Kit (DFBP20; R&amp;D systems, MN, USA), Human IL-10 Quantikine ELISA KIT (D1000B; R&amp;D systems, MN, USA), and Human Lipopolysaccharides (LPS) ELISA Kit (CSB-E09945h; Cusabio, China). Statistical significance of concentration differences between groups was determined using the Mann-Whitney U test. Results No significant difference was discovered when comparing the plasma FABP2, IL-10 and LPS concentrations between MC patients and HCs. However, FABP2 concentrations were significantly lower in the plasma of UC patients, both active (median 1272 pg/ml, p = 0,004) and inactive (median 1334 pg/ml, p = 0,001) when compared with MC patients (median 1680 pg/ml). The difference in FABP2 concentration between HCs (median 1365 mg/ml) and active or inactive UC patients did not reach statistical significance. IL-10 concentrations were significantly lower in patients with active UC (median 2,58 pg/ml) than in MC patients (3,89 pg/ml, p = 0,006) and HCs (median 4,79 pg/ml, p = 0,005). There was no significant difference between MC patients or HCs when compared with inactive UC patients (median 3,04 pg/ml). The plasma concentrations of LPS were similar across all the patient groups and no significant difference was observed. Conclusion Plasma FABP2, IL-10 and LPS did not distinguish MC patients from HCs in our study and did not show potential as biomarkers. Our results of lower plasma IL-10 concentration in patients with active UC show that it could be a useful biomarker for disease activity. It is unclear whether the lower plasma concentration of FABP2 in active UC patients compared to MC patients is important since neither group differed significantly from HCs.

Role of Circulating Microparticles in Type 2 Diabetes Mellitus: Implications for Pathological Clotting.

Type 2 diabetes mellitus (T2DM) is a multifactorial chronic metabolic disease characterized by chronic hyperglycemia due to insulin resistance and a deficiency in insulin secretion. The global diabetes pandemic relates primarily to T2DM, which is the most prevalent form of diabetes, accounting for over 90% of all cases. Chronic low-grade inflammation, triggered by numerous risk factors, and the chronic activation of the immune system are prominent features of T2DM. Here we highlight the role of blood cells (platelets, and red and white blood cells) and vascular endothelial cells as drivers of systemic inflammation in T2DM. In addition, we discuss the role of microparticles (MPs) in systemic inflammation and hypercoagulation. Although once seen as inert by-products of cell activation or destruction, MPs are now considered to be a disseminated storage pool of bioactive effectors of thrombosis, inflammation, and vascular function. They have been identified to circulate at elevated levels in the bloodstream of individuals with increased risk of atherothrombosis or cardiovascular disease, two significant hallmark conditions of T2DM. There is also general evidence that MPs activate blood cells, express proinflammatory and coagulant effects, interact directly with cell receptors, and transfer biological material. MPs are considered major players in the pathogenesis of many systemic inflammatory diseases and may be potentially useful biomarkers of disease activity and may not only be of prognostic value but may act as novel therapeutic targets.

Associations between neurofilament light chain levels, disease activity and brain atrophy in progressive multiple sclerosis.

Neurofilament light chain is a promising biomarker of disease activity and treatment response in relapsing-remitting multiple sclerosis (MS). Its role in progressive MS is less clear. The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept NEDA-3 (No Evident Disease Activity), and brain volumetry, in a cohort of patients with the progressive disease form (PMS). Levels of pNfL (SIMOA technology) were examined in 52 PMS patients and analysed in relationship to NEDA-3 status and annual brain volume loss (BVL) during the last 12 months. The statistical model was developed using logistic regression analysis, including demographic, clinical and magnetic resonance imaging (MRI) data as independent variables. Dependent variables were NEDA-3 status and BVL. The mean age of the study participants (n=52, 50% females) was 45.85 (SD, 9.82) and the median disability score was 5.0 (IQR: 5.0-5.5). ROC analysis showed that pNfL predicts NEDA-3 (the sensitivity and specificity of the model were 77.8% and 87.6%, respectively, P<0.001) and abnormal BVL (the sensitivity and specificity were 96.6% and 68.2%, respectively, P<0.001). The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA-3 status, including brain MRI-volumetry, in patients with the progressive form of MS.

Neurofilament Light Chain Levels Are Associated with Disease Activity Determined by No Evident Disease Activity in Multiple Sclerosis Patients

Introduction: There is a need for blood biomarkers of disease activity in multiple sclerosis (MS). The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept three-domain no evident disease activity (NEDA-3). Methods: Levels of pNfL (SIMOA) were examined in 159 MS patients and analyzed in relationship to NEDA-3 status (absence of relapse, disability score worsening, and brain magnetic resonance activity) during the last 12 months. The accuracy of the proposed model was evaluated by calculating the area under the receiver operating characteristics (ROC) curve. From the pNfL cutoff, we evaluated the NEDA-NfL status (no relapse, no Expanded Disability Status Scale [EDSS] worsening, and pNfL below the cutoff value). Results: Levels of pNfL were significantly higher in MS patients than in healthy controls (p < 0.001). From a total of 159 patients, 80 (50.3%) achieved NEDA-3 status, while 79 (49.7%) patients showed evident disease activity (EDA) status. pNfL were significantly lower in the NEDA-3 group than in the EDA group (pNfL mean 7.06 pg/mL [standard deviation (SD) 2.37] vs. pNfL mean 13.04 pg/mL [SD 7.07]) (p < 0.001). ROC analysis showed that pNfL predicts NEDA-3 status (sensitivity and specificity were 80.5 and 72.7%, respectively, p < 0.001), and NEDA-NfL predicts NEDA-3 status (sensitivity and specificity were 97.1 and 82.9%, respectively, p < 0.001). Conclusion: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA status in patients with MS and could be an alternative to brain magnetic resonance investigation.

Plasma neurofilament light chain levels are predictors of disease activity in multiple sclerosis as measured by four-domain NEDA status, including brain volume loss

Background: The research is focused on sensitive biomarkers in multiple sclerosis (MS). Objective: The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept NEDA (no evident disease activity), including brain volumetry, in a cohort of MS patients treated with disease-modifying treatment (DMT). Methods: Levels of pNfL (Single Molecule Array (SIMOA) technology) were examined in 95 RRMS (relapsing-remitting multiple sclerosis) patients and analyzed in relationship to NEDA-3 status and NEDA-BVL (brain volume loss; NEDA-3 extended by brain volumetry) during the last 12 months. The statistical model was developed using logistic regression analysis, including the independent variables: demographic, clinical, and magnetic resonance imaging (MRI) data. Dependent variables were NEDA-3 and NEDA-BVL status. Results: The mean age of the study participants (n = 95, 62% females) was 37.85 years (standard deviation (SD) = 9.62) and the median disability score was 3.5 (2.5–4.1). Receiver operating characteristics (ROC) analysis showed that pNfL predicts NEDA-3 (the sensitivity and specificity of the model were 92% and 78%, respectively, p < 0.001) and NEDA-BVL status (the sensitivity and specificity were 80% and 65%, respectively, p < 0.001). Conclusion: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA-BVL status, including brain MRI-volumetry in patients with RRMS.

Serum progranulin level is a novel tool for monitoring disease activity of dermatomyositis with antimelanoma differentiation‐associated protein 5 antibodies

AbstractObjectivesDermatomyositis (DM) is an autoimmune disease that presents with a wide variety of clinical manifestations. Patients with DM or clinically amyopathic dermatomyositis (CADM) with antimelanoma differentiation‐associated protein 5 (anti‐MDA5) antibodies are frequently associated with interstitial pneumonia, especially rapidly progressive interstitial lung disease. Progranulin (PGRN) is an autocrine growth factor involved in inflammation. Elevated serum PGRN levels have been reported in the patients with systemic lupus erythematosus and rheumatoid arthritis. However, they have not been precisely studied in DM/CADM. We assessed PGRN levels as a potential biomarker for DM/CADM with anti‐MDA5 antibodies.MethodsTwenty‐four DM/CADM patients with anti‐MDA5 antibodies, 12 patients without anti‐MDA5 antibodies, and eight healthy volunteers were enrolled. We measured serum PGRN levels and compared them between the anti‐MDA5 antibody‐positive and antibody‐negative groups. They were also measured before and after the start of treatment in anti‐MDA5 antibody‐positive patients. We examined the correlations between serum PGRN levels and laboratory data such as serum KL‐6 and ferritin levels.ResultsPatients with DM/CADM, especially those with anti‐MDA5 antibodies, had significantly higher serum PGRN levels than healthy individuals. They decreased after the start of treatment. Serum PGRN levels were positively correlated with serum KL‐6 and ferritin levels, and anti‐MDA5 antibody titers.ConclusionsThis is the first study to show that PGRN levels were significantly elevated in the sera of DM/CADM patients, particularly in those with anti‐MDA5 antibodies. PGRN may be a useful biomarker of disease activity. However, further studies are required to reveal the mechanisms of PGRN in DM/CADM more precisely.

Urinary soluble VCAM-1 is a useful biomarker of disease activity and treatment response in lupus nephritis

IntroductionVascular cell adhesion molecule-1 (VCAM-1) is involved in the progression of glomerular and tubulointerstitial injury in lupus nephritis (LN) and can be easily assessed in urine. The aim of this study was to assess urinary soluble VCAM-1 (uVCAM-1) as a biomarker of disease activity and treatment response in LN.MethodsThis prospective study enrolled 62 patients with class III, IV or V LN diagnosed within the last 3 years and divided them in two groups: with and without active nephritis at the inclusion, each group with 31 patients. At each visit, a urine sample was collected for uVCAM-1 evaluation and the nephritis status was assessed.ResultsMedian uVCAM-1 level was elevated in patients with active compared to inactive LN (P < 0.001). The ROC curve of uVCAM-1 demonstrated an AUC of 0.84 and a cutoff of 47.2 ng/mgCr yielded a good sensitivity (74.2%) and specificity (74.2%) for the diagnosis of active LN. A significant correlation was found between uVCAM-1 level and renal activity scores and traditional biomarkers of LN. The level of uVCAM-1 dropped in patients with active LN who went into remission (P < 0.001), increased in patients who went into activity (P = 0.002) and did not change in patients who remained inactive (P = 0.797). The level of uVCAM-1 peaked during the flare of LN (P < 0.05).ConclusionThe uVCAM-1 is a reliable biomarker that reflects renal disease activity and is useful for monitoring individual patients with lupus nephritis over time.

Apoptosis inhibitor of macrophage as a biomarker for disease activity in Japanese children with IgA nephropathy and Henoch-Schönlein purpura nephritis.

To evaluate the apoptosis inhibitor of macrophage (AIM) deposition patterns on the kidneys of children with IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) and to investigate the clinical usefulness of serum and/or urinary AIM levels as biomarkers for the disease activity. Immunohistochemical study was performed in the kidneys of 37 patients with IgAN and 10 patients with HSPN. Serum and urinary AIM levels in the patients and 20 healthy controls (HCs) were quantified by enzyme-linked immunosorbent assay. The results were compared with clinical features. In patients with IgAN and HSPN, AIM expression was observed in various areas, including the glomerular mesangial and capillary areas, the proximal and distal tubular epithelial cells, and on infiltrating macrophages in the glomeruli and interstitial areas. Serum and urinary AIM levels were significantly elevated in these patients compared with the HCs. Urinary AIM levels were positively correlated with the histological severity and degree of proteinuria and hematuria as well as urinary β2 microglobulin and urinary N-acetyl-β-D-glucosaminidase levels. AIM plays an important role in the pathogenesis of IgAN and HSPN. Urinary AIM levels can potentially reflect active renal inflammation in these diseases and may represent a useful biomarker for disease activity. Urinary AIM levels may represent a useful biomarker for disease activity of IgAN and HSPN. AIM expression was observed in the glomeruli, tubular epithelial cells, and infiltrating macrophages in glomeruli and interstitial area. U-AIM/Cr were significantly correlated not only with proteinuria, hematuria, and u-β2MG and u-NAG levels but also with the activity index of histological findings in kidney biopsy specimens. Our results can emphasize the important role of AIM in the pathogenesis of IgAN and HSPN.

Association of Circulating COMP and YKL-40 as Markers of Metabolic Changes of Cartilage with Adipocytokines in Juvenile Idiopathic Arthritis.

The aim of this study was to evaluate the association of circulating cartilage oligomeric matrix protein (COMP) and human cartilage glycoprotein-39 (YKL-40) as markers of metabolic changes of cartilage, with leptin, adiponectin, and resistin in juvenile idiopathic arthritis (JIA) patients before and after treatment. A significant decrease of COMP and an increase of YKL-4 were found in blood of untreated patients. JIA treatment leading to clinical improvement resulted in normalization of COMP levels only. Concentrations of both markers in treated patients, while showing no clinical improvement, differed from those in controls and patients with remission. The leptin level decreased (p < 0.05) in untreated patients; however, concentrations of adiponectin and resistin increased (p < 0.05) as compared to controls. JIA treatment resulted in normalization of adipocytokine levels in remissive patients but not those with active JIA. Untreated patients showed a correlation between COMP and leptin, adiponectin, and body mass index (BMI) and between YKL-40 and leptin, adiponectin, BMI, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). In inactive JIA, a correlation between YKL-40 and leptin was shown. Treated patients with an active JIA demonstrated a correlation between COMP and adiponectin and between YKL-40 and leptin, adiponectin, BMI, CRP, and ESR. The results of this work indicate that leptin and adiponectin but not resistin may be involved in the development and progression of joint dysfunction in JIA. Additionally, we suggest that YKL-40 may be a useful biomarker of disease activity and may be used to assess treatment towards remission, as compared to COMP.

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

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. 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. 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. 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.

Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD.

To test the hypothesis that serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), which are an intermediate astrocyte and neuron filaments, respectively, are clinically useful biomarkers of disease activity and disability in neuromyelitis optica spectrum disorders (NMOSD). Levels of GFAP and NfL in serum (sGFAP and sNfL, respectively) and in CSF samples were measured in healthy controls (HCs) (n = 49; 49 serum samples), patients with NMOSD (n = 33; 42 CSF and 102 serum samples), and patients with multiple sclerosis (MS) (n = 49; 53 CSF and 91 serum samples) by ultrasensitive single-molecule array assays. Association of sGFAP and sNfL levels with clinical parameters was determined. For both GFAP and NfL, CSF and serum levels were strongly correlated. Both were higher in the serum of patients with NMOSD than in HCs (both p < 0.001). Moreover, sGFAP was higher in NMOSD than in MS (median 207.7 vs 121.1 pg/mL, p < 0.001). In NMOSD, sGFAP concentration increased after recent relapse (540.9 vs 152.9 pg/mL, p < 0.001). Multivariate analyses indicated that sGFAP and sNfL were associated with Expanded Disability Status Scale score in NMOSD (p = 0.026 and p < 0.001, respectively). Higher sGFAP/sNfL quotient at relapse differentiated NMOSD from MS with a sensitivity of 73.0% and a specificity of 75.8%. sGFAP and sNfL are likely to be good biomarkers of disease activity and disability, and the sGFAP/sNfL quotient at relapse is a potential diagnostic marker for NMOSD.

YKL-40 as a new biomarker of disease activity in Takayasu arteritis

ObjectiveTo evaluate the role of YKL-40 as a biomarker of disease activity in patients with Takayasu arteritis (TA). MethodsThe study included 40 patients diagnosed with TA between January 2017 and January 2018. 40 age and sex matched healthy controls were included. Serum levels of YKL-40, as well as IL-6, IL-8, IL-17, sCD163, VEGF, MMP-2, MMP-9, OPN, PTX-3 and IFN-γ, were detected at the base line and end of the 6-month follow-up. Modified Kerr criteria, in which MRA was performed instead of traditional angiography, was used a standard measure of disease activity. The association of the measured biomarkers with disease activity was analysed. ResultsThe serum levels of YKL-40, IL-6, IL-8, IFN-γ, MMP-2, MMP-9, PTX-3 and OPN were significantly higher in active disease than in inactive disease. Significant differences in the serum levels of YKL-40, IL-6 and PTX-3 were also observed according to the disease activity degree. Logistic analysis demonstrated that high YKL-40 levels and high IL-6 levels were independent risk factors for active disease. When YKL-40 was combined with IL-6, the specificity and sensitivity for detecting active disease were increased (87.6% and 70.4% respectively); similar findings were obtained when YKL-40 was combined with CRP (72.3% and 84.6% respectively). A predictive model of active disease using ESR, CRP, IL-6, PTX-3 and MMP-9 showed significantly improved diagnostic efficiency when YKL-40 was added to the model (sensitivity: 85.1%; specificity: 94.3%; NRI value: 12.4%; IDI value: 4.6%, p < 0.05). ConclusionsSerum YKL-40 concentrations may be a useful biomarker of disease activity in TA.

The miRNA Expression Profile of Experimental Autoimmune Encephalomyelitis Reveals Novel Potential Disease Biomarkers

Multiple sclerosis (MS) is a debilitating autoimmune disease affecting over 2.3 million people worldwide, and it is characterized by inflammation and demyelination of nerve cells. The currently available biomarkers for the diagnosis and management of MS have inherent limitations, therefore, additional new biomarkers are needed. We studied the microRNA (miRNA) profile of splenocytes of mice having experimental autoimmune encephalomyelitis (EAE), a model of human MS. A miRNA-microarray analysis revealed increased expression of nine miRNAs (let-7e, miR-23b, miR-31, miR-99b, miR-125a, miR-146b, miR-155, miR-193b, and miR-221) following EAE development. Interestingly, serum levels of miR-99b, miR-125a, and miR-146b were significantly higher in EAE mice compared to normal mice. Bioinformatics analysis revealed the experimentally validated as well as predicted gene targets of specific miRNAs that are important for disease progression in MS. Specifically, we observed inverse correlation in the levels of miR-99b versus LIF, and between miR-125a versus BDNF and LIF. Our results suggest that above-mentioned miRNAs may play a crucial role in the pathogenesis of MS, and that miR-99b, miR-125a, and miR-146b in particular may serve as useful biomarkers for disease activity.

Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis

BackgroundThere is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and other biomarkers, subsequent disease activity, and brain volume loss in CIS and RRMS.MethodsA panel of neurodegenerative and neuroinflammatory markers were analyzed in repeated CSF samples from 41 patients with CIS or RRMS in a prospective longitudinal cohort study and from 22 healthy controls. NFL in serum was analyzed using a single-molecule array (Simoa) method. “No evidence of disease activity-3” (NEDA-3) status and brain volume (brain parenchymal fraction calculated using SyMRI®) were recorded during 4 years of follow-up.ResultsNFL levels in CSF and serum correlated significantly (all samples, n = 63, r 0.74, p < 0.001), but CSF-NFL showed an overall stronger association profile with NEDA-3 status, new T2 lesions, and brain volume loss. CSF-NFL was associated with both new T2 lesions and brain volume loss during follow-up, whereas CSF-CHI3L1 was associated mainly with brain volume loss and CXCL1, CXCL10, CXCL13, CCL22, and MMP-9 were associated mainly with new T2 lesions.ConclusionsSerum and CSF levels of NFL correlate, but CSF-NFL predicts and reflects disease activity better than S-NFL. CSF-NFL levels are associated with both new T2 lesions and brain volume loss. Our findings further add to the accumulating evidence that CSF-NFL is a clinically useful biomarker in CIS and RRMS and should be considered in the expanding NEDA concept. CSF-CXCL10 and CSF-CSF-CHI3L1 are potential markers of disease activity and brain volume loss, respectively.