Potential Marker Of Disease Activity Research Articles

Cell Free DNA in SLE Patients: A Possible Marker of Disease Activity and Organ Damage

Abstract Background Systemic lupus erythematous (SLE) is a prototypic autoimmune disease with a complex pathogenesis involving multiple genetic and environmental factors. Cell death has been regarded as an important event in lupus pathogenesis as it leads to release of antigens as nucleic acids for immune complex formation. DNA-antibody complex in the circulation are one of the hallmarks of SLE that leads to detrimental effects causing manifestations of SLE. Fluctuation in circulating DNA level might be one of the driving factors behind flare-ups of SLE. Objectives This study aims to measure the circulating cell free DNA (cf-DNA) in patients with SLE as a potential marker for disease activity and organ damage. Methods This case control study included 100 participants categorized into 75 SLE patients as patient group (Group I), further divided to 39 SLE patients without therapy (group Ia), 36 SLE patients with therapy (Group Ib) and 25 age and sex matched healthy subjects as a control group (Group II). All participants were subjected to full history taking, thorough rheumatological examination and lab assessment of complete blood count (CBC), ESR, CRP, C3, C4 levels, ANA titer, anti-ds-DNA concentration by ELIZA and measurement of plasma cf-DNA levels by real time PCR. Cf- DNA concentration is expressed as concentration (ng/ml). Results SLE patients (Group Ia and Ib) showed significant increase in (plasma cf-DNA,CRP, ESR, ANA, anti-ds-DNA), significant decrease in (C3 and C4, hemoglobin, total leucocytic count and platelet count). Plasma cf-DNA (ng/ml) was significantly lower in group Ib compared to group Ia. There was significant positive correlation between plasma cf-DNA (ng/ml) and levels of ANA and anti-ds-DNA in all SLE patients and with SLEDAI-2k score in all patients. Conclusion Plasma level of cf-DNA is significantly increased in SLE patients especially before starting therapy these data may suggest it to be a possible marker of treatment follow up. Further studies on a larger patient population are still needed to confirm these results.

Insight into the Interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in IgA Vasculitis (IgAV).

The pathogenesis of IgAV, the most common systemic vasculitis in childhood, appears to be complex and requires further elucidation. We aimed to investigate the potential role of galactose-deficient immunoglobulin A1 (Gd-IgA1), high-mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE) and protocadherin 1 (PCDH1) in the pathogenesis of IgAV. Our prospective study enrolled 86 patients with IgAV and 70 controls. HMGB1, RAGE, Gd-IgA1 and PCDH1 in serum and urine were determined by the enzyme-linked immunosorbent assay (ELISA) method at the onset of the disease and after a six-month interval in patients and once in the control group. Serum concentrations of HMGB1, RAGE and PCDH1 and urinary concentrations of HMGB1, RAGE, Gd-IgA1 and PCDH1 were significantly higher in patients with IgAV than in the control group (p < 0.001). Concentrations of HMGB1 (5573 pg/mL vs. 3477 pg/mL vs. 1088 pg/mL, p < 0.001) and RAGE (309 pg/mL vs. 302.4 pg/mL vs. 201.3 pg/mL, p = 0.012) in the serum of patients remained significantly elevated when the disease onset was compared with the six-month follow-up interval, and thus could be a potential marker of disease activity. Urinary concentration of HMGB1 measured in the follow-up period was higher in patients with nephritis compared to IgAV without nephritis (270.9 (146.7-542.7) ng/mmol vs. 133.2 (85.9-318.6) ng/mmol, p = 0.049) and significantly positively correlated with the urine albumine to creatinine ratio (τ = 0.184, p < 0.05), the number of erythrocytes in urine samples (τ = 0.193, p < 0.05) and with the outcome of nephritis (τ = 0.287, p < 0.05); therefore, HMGB1 could be a potential tool for monitoring patients with IgAV who develop nephritis. Taken together, our results imply a possible interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in the development of IgAV. The identification of sensitive biomarkers in IgAV may provide disease prevention and future therapeutics.

Myostatin and Activin A as Biomarkers of Sarcopenia in Inflammatory Bowel Disease Patients.

The prevalence of sarcopenia in inflammatory bowel disease patients has received increasing attention. The aim of this study is to assess the usefulness of determining levels of myostatin (MSTN) and activin A (Act A) as potential markers of disease activity and occurrence of sarcopenia in Crohn's disease and ulcerative colitis patients. The case-control study included 82 patients with Inflammatory Bowel Disease. The control group consisted of 25 healthy volunteers. The serum levels of myostatin and activin A were determined by the quantitative sandwich enzyme-linked immunosorbent assay. Sarcopenia was diagnosed based on the EWGSOP2 criteria. The study found lower levels of myostatin and activin A in the IBD patients. There were significantly lower levels of myostatin (80.6 pg/mL vs. 186.2 pg/mL; p = 0.0364) as well as activin A (32.1 pg/mL vs. 35.2 pg/mL; p = 0.0132) in the IBD patients with sarcopenia compared to those without sarcopenia. Positive correlations were found between MSTN levels and Muscle Mass Index (rho = 0.31; p < 0.005) and hand grip strength (rho = 0.34, p < 0.05) in the IBD patients. The determination of serum levels of MSTN and Act A may be useful in the early diagnosis of sarcopenia in IBD patients.

Markedly upregulated serum semaphorin 4A as a novel activity marker of myasthenia gravis.

Myasthenia gravis (MG) is an autoantibody-mediated disease of the neuromuscular junction. Semaphorin 4A (Sema4A) is involved in the activation of T cells in various inflammatory disorders. In this study, we aimed to investigate whether Sema4A is involved in the pathogenesis of MG. We measured serum Sema4A concentrations in 30 treatment-naïve MG patients with acetylcholine receptor (AChR) antibodies, 7 with muscle-specific tyrosine kinase (MuSK) antibodies and 21 normal controls. As a result, serum Sema4A levels were significantly higher in patients with AChR antibody-positive MG and MuSK antibody-positive MG than in controls (p ≤ 0.0001 for both MG groups). Serum Sema4A levels were correlated with AChR antibody levels (Spearman's ρ = 0.39, p = 0.03) and MG Foundation of America clinical classification classes (Spearman's ρ = 0.38, p = 0.04) in patients with AChR antibody-positive MG. In conclusion, high serum Sema4A levels may reflect T-cell activation, and this molecule could be a potential marker of disease activity in MG.

Reversibility of the Enlargement of the Pulmonary Artery in COVID-19 Pneumonia as a Marker of Remission of the Disease.

Coronavirus disease 2019 (COVID-19) pneumonia is associated with extensive pulmonary microangiopathy and the enlargement of the pulmonary artery (PA), while its progression after the remission of the disease has not been investigated yet. The aim was to assess the diametral increase in the PA in COVID-19 pneumonia, as revealed on chest computed tomography (CT), and further investigate its progression. This was a retrospective cohort study of patients with COVID-19 pneumonia, without prior history of pulmonary hypertension, who underwent CT pulmonary angiography before, during, and after the infection. Pulmonary embolism was excluded in all cases. The main PA diameter (MPAD) was assessed in consecutive chest imaging. Statistical analysis was performed with the non-parametric Wilcoxon and Kruskal-Wallis tests, while correlations were performed with the non-parametric Spearman test. A mean ± SD MPAD of 3.1 ± 0.3 cm in COVID-19 pneumonia was significantly decreased to 2.8 ± 0.3 cm in the post-infectious state after 2-18 months in 31 patients (p-value: <0.0001). In a subgroup of six patients with more than one post-COVID-19 CT, a significant further decline in the diameter was observed (p-value: 0.0313). On the other hand, in accordance with the literature, a significant increase in the MPAD during COVID-19 pneumonia was noted in a group of 10 patients with a pre-COVID-19 CT (p-value: 0.0371). The enlargement of the PA is a common finding in COVID-19 pneumonia that regresses after the remission of the disease, indicating that this reversible cardiovascular event is a potential marker of disease activity, while its course in long COVID is yet to be determined.

Plasma Circular-RNA 0005567 as a Potential Marker of Disease Activity in Rheumatoid Arthritis.

Circular RNAs (circRNAs) are noncoding molecules and are generated through back splicing, during which the 5' and 3' ends are covalently joined. Consequently, the lack of free ends makes them stable and resistant to exonucleases, and they become more suitable biomarkers than other noncoding RNAs. The aim of the study was to find an association between selected circRNAs and disease activity in patients with RA. A total of 71 subjects, 45 patients with RA and 26 healthy controls (HCs), were enrolled. In the RA group, 24 patients had high disease activity (DAS-28-ESR > 5.1) and 21 individuals were in remission (DAS-28-ESR ≤ 2.6). The cell line SW982 was used to evaluate the biological function of circ_0005567. The concentration of circ_0005567 in RA patients was elevated compared to HCs (median, 177.5 [lower-upper quartile, 83.13-234.6] vs. 97.83 [42.03-145.4], p = 0.017). Patients with high disease activity had a higher concentration of circ_0005567 than the control group (185.4 [112.72-249.25] vs. 97.83 [42.03-145.4], p = 0.015). In the cell line model, we found an association between circ_0005567 and miR-194-5p concentration and increased expression of mRNAs that may be related to cell proliferation. The plasma concentration of circ_0005567 may be a new potential biomarker associated with disease activity in patients with RA.

The interplay of oxidative stress and inflammation in pediatric patients with nephrotic syndrome

Summary &#x0D; Background: The pathophysiological mechanisms crucial in the development of nephrotic syndrome (NS) in the pediatric population are still not fully understood. This study aims to investigate the synergistic interaction of oxidative stress and inflammation in the pathogenesis of NS. Additionally, one of the objectives of this study is to examine the relationship between hypertension and the degree of oxidative stress and inflammation in patients during the acute phase of the disease. &#x0D; Methods: The study included 33 children, aged 2 to 9 years, with NS. Blood samples were collected during the acute phase and remission. Parameters of oxidative status were determined, including total oxidative status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), sulfhydryl groups (-SH), paraoxonase 1 (PON1), and total antioxidant status (TAS) in serum, measured spectrophotometrically. Inflammatory parameters such as pentraxin 3 (PTX3), leptin, programmed cell death ligand 1 (PD-L1), and E-cadherin were determined using enzyme-linked immunosorbent assay (ELISA).&#x0D; Results: Patients with NS and hypertension had significantly higher levels of AOPP and TOS (p=0.029 and p=0.003, respectively). During the acute phase of the disease, lower activity of -SH and PON1 was observed compared to remission (p&lt;0.001, for both). PTX3 levels were higher, while leptin levels were lower during the acute phase (p&lt;0.001, for both). PTX3 correlated with AOPP and TAS during the acute phase but not in remission (rs=0.42, p=0.027 and rs=0.43, p=0.025, respectively). A negative correlation between AOPP and leptin was observed during the acute phase, which disappeared in remission (rs=-0.42, p=0.028).&#x0D; &#x0D; Conclusions: Results of this study show that hypertension influences oxidative stress markers, and decreased antioxidant capacity may contribute to NS development. PTX 3 appears as a potential disease activity marker, indicating a dynamic connection between inflammation and oxidative stress. Leptin may also play a role in oxidative stress in NS. &#x0D; List of abbreviations: AOPP, advanced oxidation protein products; BMI, body mass index; DBP, diastolic blood pressure; ELISA, enzyme-linked immunosorbent assay; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; total antioxidant status; PAB, prooxidant-antioxidant balance; -SH, sulfhydryl group; SBP, systolic blood pressure; PON 1, paraoxonase; PTX 3, pentraxin 3; PD-L1, programmed cell death ligand 1; TC, total cholesterol; TG, triglyceride; TAS, total antioxidant status; TOS, total oxidation status.&#x0D;

MRI ankle in juvenile idiopathic arthritis and its comparison with clinical disease activity scores

Objectives: Juvenile idiopathic arthritis (JIA) is a common cause of morbidity and consequent disability among youth up to 16 years of age. Our study aims to image the ankle joints of JIA patients and correlate the findings with the clinical disease activity scores. Juvenile Arthritis Disease Activity Score (JADAS-27) is used by pediatricians to assess disease activity in JIA patients. There are four factors that determine this score – Global assessment of disease activity by the physician as well as patient/parent, joint count with active disease, and erythrocyte sedimentation rate (ESR). However, these clinical scores are dependent on the clinician’s experience and observation and, therefore, subjective. Material and Methods: Thirty patients of either sex with a clinical diagnosis of JIA as per the International League of Association for Rheumatology definition with clinically involved ankle joints were included in the study. Chronic arthritis due to other causes, such as infection, trauma, and so on, was excluded. All clinically diagnosed cases of JIA were subjected to magnetic resonance imaging (MRI) evaluation on Siemens Skyra 3 Tesla High-Resolution MR system using a dedicated coil for the ankle joint. Six sub-joints for each patient are evaluated, namely - The tibiotalar joint, subtalar joint, calcaneocuboid joint, calcaneonavicular joint, naviculocuneiform joint, and tarsometatarsal joint. Image analysis and scoring shall be done for each patient at each joint as per the Juvenile Arthritis MRI SCORE, consisting of the following parameters-synovial hypertrophy score, cartilage lesion score, bone erosion score, and bone marrow change score. Each of these scores is calculated individually based on the percentage of involved bone volume. All individual scores were summed to get the total MRI Score. The data collected were then statistically analyzed. Results: A positive correlation was sought between the JADAS-27 score and the total MRI score with the P-value being 0.03. A positive correlation was also found between the total MRI score and the ESR value of the patient (P - 0.02). Conclusion: MRI findings can be a potential marker of disease activity in JIA patients and these findings could also predict the prognosis accurately in these patients. The findings are objective and comparable to the aforementioned clinical scores.

Clinical study of carotid superb microvascular imaging in evaluating the activity of Takayasu's arteritis.

The goal of this study is to use superb microvascular imaging (SMI) to observe neovascularization in the carotid vessel wall to identify potential Takayasu's arteritis (TAK) inflammation markers. Bilateral carotid arteries from 96 patients with TAK were imaged by a Doppler ultrasound and SMI. The one-way analysis of variance (ANOVA) was used to document significant differences between the activity and inactivity stages of TAK and the factors closely related to its activity in the binary logistics regression equation. Clinical and laboratory data included age, gender, duration of disease, treatment history, NIH score, erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein. Imaging data included the arterial wall thickness, degree of lesion, SMI grade, and arterial aneurysm formation. There were 45 patients in the active TAK stage and 51 in the inactive stage. The one-way ANOVA showed significant differences in SMI (p = 0.001) and ESR (p = 0.022) between the active and inactive groups. The binary logistics regression analysis showed that SMI was an independent risk factor for TAK activity (B = -1.505, S.E = 0.340, Wald = 19.528, OR = 0.222 95%, CI = 0.114-0.433, p < 0.01). Using SMI G1 or G2 as the cutoff values for the diagnosis of active TAK, the positive predictive value, sensitivity, and specificity were 60 and 86%, 84% and 56%, and 54% and 92%, respectively. The SMI grade is a potential marker of disease activity in patients with TAK.

Serum Elafin as a Potential Marker of Disease Activity in Behçet's Disease.

Elafin is a serine protease inhibitor with anti-inflammatory properties. It is expressed in various epithelial tissues with increased production under inflammatory conditions. Increased tissue elafin expression in Behçet's disease (BD) lesions has previously been demonstrated. We hypothesised that serum elafin might be increased in patients with BD and aimed to assess the relationship of serum elafin with disease activity and organ involvement in BD. Fifty-four BD patients (29 active, 25 inactive) and 30 healthy controls were included in this single-centre case-control study. Serum elafin was measured using ELISA. Complete blood count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) tests were also performed. Serum elafin levels were significantly higher in patients with BD (1.58 ± 0.47 ng/ml, range: 0.67-2.96) compared to controls (1.10 ± 0.28 ng/ml, range: 0.65-1.49) (P < 0.001). Patients with active BD had higher elafin levels than patients with inactive BD (P = 0.008). Active arthritis was associated with an increase in elafin (P = 0.012), while the presence of mucocutaneous symptoms was not. Serum elafin correlated significantly with ESR (P = 0.001). The ideal cut-off value for the diagnosis of BD was determined as 1.24 ng/ml with a sensitivity and specificity of 72.2% and 70.0%, respectively. Serum elafin is significantly increased in patients with BD. It may serve as a marker of disease activity, especially articular involvement.

The role of microRNAs in regulating inflammation and exercise-induced adaptations in rheumatoid arthritis.

MicroRNAs (miRNAs) are endogenously generated single-stranded RNAs that play crucial roles in numerous biological processes, such as cell development, proliferation, differentiation, metabolism and apoptosis. They negatively regulate target gene expression by repressing translation of messenger RNA into a functional protein. Several miRNAs have been implicated in the development and progression of RA. They are involved in inflammatory and immune processes and are associated with susceptibility to RA and disease activity. They are also considered to be potential markers of disease activity or even therapeutic targets. Likewise, several miRNAs are affected acutely by exercise and regulate exercise-related adaptations in the skeletal muscle and cardiovascular system and aerobic fitness. Interestingly, some miRNAs affected by exercise are also important in the context of RA. Investigating these might increase our understanding of the effects of exercise in RA and improve exercise prescription and, potentially, disease management. In this review, we focus on the miRNAs that are associated with both RA and exercise and discuss their roles in (and potential interactions between) RA and exercise-induced adaptations.

The intracellular signaling pathways governing macrophage activation and function in human atherosclerosis.

Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and plaque formation in arterial vessel walls. Atherosclerotic plaques narrow the arterial lumen to increase the risk of heart attacks, ischemic stroke and peripheral vascular disease, which are major and worldwide health and economic burdens. Macrophage accumulation within plaques is characteristic of all stages of atherosclerosis and their presence is a potential marker of disease activity and plaque stability. Macrophages engulf lipids and modified lipoproteins to form foam cells that express pro-inflammatory and chemotactic effector molecules, stress inducing factors and reactive oxygen species. They control plaque stability and rupture through secretion of metalloproteinases and extracellular matrix degradation. Although macrophages can worsen disease by propagating inflammation, they can stabilize atherosclerotic plaques through tissue remodeling, promoting the formation of a fibrous cap, clearing apoptotic cells to prevent necrotic core formation and through vascular repair. In atherosclerosis, macrophages respond to dyslipidaemia, cytokines, dying cells, metabolic factors, lipids, physical stimuli and epigenetic factors and exhibit heterogeneity in their activation depending on the stimuli they receive. Understanding these signals and the pathways driving macrophage function within developing and established plaques and how they can be pharmacologically modulated, represents a strategy for the prevention and treatment of atherosclerosis. This review focusses on the current understanding of factors controlling macrophage heterogeneity and function in atherosclerosis. Particular attention is given to the macrophage intracellular signaling pathways and transcription factors activated by biochemical and biophysical stimuli within plaques, and how they are integrated to regulate plaque formation and stability.

Neutrophil-Lymphocyte Ratio and Platelat-Lymphocyte Ratio as Potential Markers of Disease Activity in Patients with Axial Spondyloarthritis

Neutrophil-Lymphocyte Ratio and Platelat-Lymphocyte Ratio as Potential Markers of Disease Activity in Patients with Axial Spondyloarthritis

Altered fecal short‑chain fatty acid profile as a potential marker of disease activity in patients with ulcerative colitis and Crohn's disease: a pilot study.

Altered fecal short‑chain fatty acid profile as a potential marker of disease activity in patients with ulcerative colitis and Crohn's disease: a pilot study.

Beyond Systemic Lupus Erythematosus and Anti-Phospholipid Syndrome: The Relevance of Complement From Pathogenesis to Pregnancy Outcome in Other Systemic Rheumatologic Diseases.

Evidence about the relevance of the complement system, a highly conserved constituent of the innate immunity response that orchestrates the elimination of pathogens and the inflammatory processes, has been recently accumulated in many different rheumatologic conditions. In rheumatoid arthritis, complement, mainly the classical pathway, contributes to tissue damage especially in seropositive subjects, with complement activation occurring in the joint. Data about complement pathways in psoriatic arthritis are dated and poorly consistent; among patients with Sjögren syndrome, hypocomplementemia exerts a prognostic role, identifying patients at risk of extra-glandular manifestations. Hints about complement involvement in systemic sclerosis have been recently raised, following the evidence of complement deposition in affected skin and in renal samples from patients with scleroderma renal crisis. In vasculitides, complement plays a dual role: on one hand, stimulation of neutrophils with anti-neutrophil cytoplasmic antibodies (ANCA) results in the activation of the alternative pathway, on the other, C5a induces translocation of ANCA antigens, favouring the detrimental role of antibodies. Complement deposition in the kidneys identifies patients with more aggressive renal disease; patients with active disease display low serum levels of C3 and C4. Even though in dermatomyositis sC5b-9 deposits are invariably present in affected muscles, data on C3 and C4 fluctuation during disease course are scarce. C3 and C1q serum levels have been explored as potential markers of disease activity in Takayasu arteritis, whereas data in Behçet disease are limited to in vitro observations. Pregnancies in women with rheumatologic conditions are still burdened by a higher rate of pregnancy complications, thus the early identification of women at risk would be invaluable. A fine-tuning of complement activation is required from a physiological progression of pregnancy, from pre-implantation stages, through placentation to labour. Complement deregulation has been implicated in several pregnancy complications, such as recurrent abortion, eclampsia and premature birth; low complement levels have been shown to reliably identify women at risk of complications. Given its physiologic role in orchestrating pregnancy progression and its involvement as pathogenic effector in several rheumatologic conditions, complement system is an attractive candidate biomarker to stratify the obstetric risk among women with rheumatologic conditions.

Chemokine CXCL1 as a potential marker of disease activity in systemic lupus erythematosus

ObjectivesThe chemokine CXCL1, known as growth-related oncogene α (GRO-α), is a potent chemoattractant and regulator of neutrophils. The purpose of our study was to evaluate the regulatory response of CXCL1 in the serum of patients with systemic lupus erythematosus (SLE) in the active stage of disease and to assess whether it was implicated in the pathogenesis/inflammatory process in lupus.MethodsCXCL1 serum concentrations were examined in 90 SLE patients, 56 other autoimmune diseases (OADs) patients and 100 healthy controls using enzyme-linked immunosorbent methodology.ResultsSLE patients exhibited significant increases in serum CXCL1 concentrations [1492.86 (735.47–2887.34) pg/ml] compared with OADs patients [155.88 (10.77–366.78) pg/ml] and healthy controls [13.58 (8.46–37.22) pg/ml] (p < 0.001). Moreover, the level of CXCL1 decreased as the level of anti-dsDNA IgG decreased after treatment between the anti-dsDNA-positive SLE patients and the anti-dsDNA-negative SLE patients. Additionly, serum CXCL1 concentrations were related to different disease activity levels in SLE and lupus nephritis (LN) and high avidity of IgG ANAs (HA IgG ANAs) (p < 0.05). Furthermore, CXCL1 serum concentrations were significantly correlated with the SLE Disease Activity Index(SLEDAI) score, relative avidity index (RAI) of HA IgG ANAs and the levels of anti-dsDNA IgG, CRP, ESR, albumin, C3 and C4.Additionally, Statistical analysis revealed that positivity for IgG ANA (p < 0.001), the presence of HA IgG ANAs (p = 0.001) and the logarithmic level of anti-dsDNA IgG (p = 0.021) were significantly associated with the logarithmic level of CXCL1 with standard partial regression coefficients (95% CI) of 2.371 (1.734–3.009), 1.231 (0.52–1.937) and 0.409 (0.062–0.755), respectively. Finally, using cutoff points of 1182.17 pg/mL and 1500.31 pg/mL, serum CXCL1 levels had a similar sensitivity of 76% and specificity of 100% and 75% for the diagnosis of active SLE and LN, respectively.ConclusionsSerum CXCL13 concentrations might represent a potential marker of disease activity in systemic lupus erythematosus.

P030 Chemokines and Adipokines As Biomarkers of Crohn's Disease Activity: A Systematic Review Of The Literature.

Crohn's disease (CD) is an inflammatory bowel disease (IBD) that can affect the entire gastrointestinal tract and can have a major impact on the patient's quality of life. Asymptomatic patients, or those with mild symptoms, experience the active disease with subclinical manifestation. A systematic review (SR) was performed to look for evidence for the role of chemokines and adipokines as markers for CD activity. This SR was conducted by searching published studies in international and regional databases up to July 2020. CD patients were adults with the disease in activity or remission. All adipokines and chemokines were considered for the analysis and the Rayyan QCRI system was used. The selection of articles published in the Rayyan system was carried out by two reviewers, autonomously and independently, and a third reviewer was responsible for analysing and deciding on the inclusion or exclusion of the article, especially in relation to those who presented a contradictory and conflicting decision. The search for articles was carried out in the databases PUBMED, PUBMED PM C, BVSBIREME, SCOPUS, WEB OF SCIENCE, EMBASE, COCHRANE, EBSCOHOST, PROQUEST and ENDNOTE WEB. The keywords "Crohn's disease", "chemokines", "adipokines", "biomarkers" and "inflammation" were chosen after reading material related to the researched topic. To expand and guide the search, an association of the descriptors was carried out by means of Boolean operators "OR" and "AND". The Boolean operators "OR" and "AND" were used to add or restrict the search, as follows: "Crohn Disease AND Biomarkers AND (Chemokines OR Adipokines) AND Inflammation". Only studies with human samples were considered. In total, 20 studies were included from 344 which were found in the databases. Six addressed chemokines and eight adipokines as potential biomarkers of CD activity. CXCL8 was the most studied chemokine (8 studies) and the results were controversial, with 62.5% showing a significant association with CD activity. CXCL10 was investigated by 4 studies and 50% identified it as a potential biomarker. CCL2, CCL11, CCL26 and CXCL1 were examined by 2 articles each. CXCL8 (P=0.002/P=0.001) and CXCL1 (P < 0.001) presented the lowest P value, which qualifies them as potential markers of disease activity. All the adipokines were tested in peripheral blood but 44.4% were also tested in intestinal mucosa, while the percentage in the chemokines' studies was 76.9% in peripheral blood, 46.1% in intestinal mucosa and 7.6% in urine sample respectively. Despite the limitations and the small number of studies found in the literature that followed the criteria of this SR, some chemokines (CCL2, CCL20, CXCL1, CXCL3, CXCL8, CXCL10 and CXCL1) and adipokines (leptin, IL-6 and TNF-α) have unveiled promising results that may enable us to distinguish active versus in remission forms of CD based on objective criteria of inflammation such as endoscopic, histologic or radiological criteria. The development of disease activity biomarkers for CD is becoming relevant for clinical practice, and chemokines and adipokines have the potential to signalize CD activity. However, validation in larger cohorts of patients, preferable multicenter studies are still needed.

Neutrophil-lymphocyte, platelet-lymphocyte and lymphocyte-monocyte ratios may not be useful markers to assess disease activity in rheumatoid arthritis: A STROBE-compliant article.

The associations among the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) and disease activity in rheumatoid arthritis remains unclear.To evaluate these indicators as potential markers of disease activity in patients with rheumatoid arthritis (RA).This cross-sectional study included 547 adult patients with RA. The patients were divided into two groups according to the disease activity score (DAS) system: remission and disease activity. Differences in the NLR, PLR and LMR of the two groups were assessed. Correlations were analyzed using Spearman analysis, and receiver operating characteristic (ROC) curves were used to identify the sensitivity, specificity, and optimal cutoff values to differentiate active RA patients from inactive RA patients.There was a statistically significant difference in the NLR (4.2 ± 3.2 vs 3.4 ± 2.4, P = .034) and PLR (222.3 ± 136.4 vs 176.9 ± 89.8, P = .006) between the two groups, but not for the LMR (3.0 ± 1.8 vs 3.4 ± 2.4, P = .115). In addition, the DAS28 and traditional inflammatory markers, including ESR and CRP, were weakly positively correlated with the NLR and PLR. Based on the ROC curves, the NLR (sensitivity 31.8%, specificity 77.8%) and PLR (sensitivity 57.3%, specificity 63.9%) were less valuable than the ESR (sensitivity 67.2%, specificity 91.7%) and CRP (sensitivity 76.2%, specificity 91.7%) for differentiating inactive RA patients from active RA patients due to low sensitivity and specificity and combining NLR or PLR also cannot significantly improved the diagnostic value of ESR and CRP.NLR, PLR and LMR may not be an useful independent diagnostic or complementary marker for disease activity in RA patients.

Subclinical entheseal involvement in patients with rheumatoid arthritis

BackgroundEnthesopathy is a common feature of Spondyloarthritis (SpA) but can also be found in rheumatoid Arthritis (RA). Recognizing enthesopathy could be challenging because of low sensitivity and specific clinical testing. To detect enthesopathy, The European League Against Rheumatism (EULAR) recommends magnetic resonance imaging (MRI) or ultrasonography (US). Aim of the workTo investigate the frequency and distribution of entheseal involvement in RA patients and its relation to disease activity. Patients and methods100 RA patients with any symptom in foot and ankle were enrolled. Disease activity score (DAS28), Visual analogue scale (VAS), Health assessment questionnaire-Disability index (HAQ-DI) and Glasgow Ultrasound Enthesitis Scoring System (GUESS) were assessed. ResultsThe mean age of patients was 44.1 ± 12.2 years, disease duration was 7 ± 5.8 years and 86% were females. The mean DAS28 score was 4.3 ± 1.2 and GUESS score was 7.2 ± 4.2; all patients had variable degrees of enthesitis: 30% of patients had mild enthesitis, 42% had moderate enthesitis and 28% had marked enthesitis. GUESS was significantly higher in patients with moderate (7.8 ± 4.9) and high (7.2 ± 3.2) disease activity than in patients with low disease activity (5.2 ± 3.9) and those in remission (6.5 ± 1.9) (p = 0.015). HAQ, Age and ESR significantly correlated with GUESS score (r = 0.19, p = 0.049; r = 0.23, p = 0.023; r = 0.33, p = 0.001 respectively). ConclusionSubclinical enthesitis is remarkable in RA patients. Quadriceps tendon enthesis was mostly affected. Enthesitis is significantly related to age, ESR and HAQ. The presence of enthesitis in RA may represent a potential marker for disease activity.

Alternative Complement Pathway Is Activated and Associated with Galactose-Deficient IgA1 Antibody in IgA Nephropathy Patients.

BackgroundGalactose-deficient IgA1 (Gd-IgA1) and alternative complement pathway activation are considered to be involved in the pathogenesis of IgA nephropathy (IgAN). Nevertheless, the relationships between alternative pathway activation and disease activity or Gd-IgA1 level remains unclear.MethodsNinety-eight biopsy-diagnosed IgAN, twenty-five primary focal segmental sclerosis (FSGS) patients and forty-two healthy individuals were recruited in this study. Among them, fifty IgAN patients received immunosuppression. Follow-up blood samples at 1 and 3~6 months after immunosuppression were collected. Plasma levels of complement C5a, factor Ba and Gd-IgA1 were measured and analyzed. Immunostaining for complement was performed in twenty-five IgAN and FSGS patients.ResultsAt baseline, IgAN patients had higher levels of plasma C5a, factor Ba and Gd-IgA1 than control subjects. Gd-IgA1 levels positively correlated with plasma C5a and factor Ba. In addition, levels of factor Ba and Gd-IgA1 were positively associated with proteinuria and negatively associated with renal function. Immunostaining revealed positive staining for factor Bb and C3c in glomeruli in IgAN patients, but not in FSGS patients. At baseline, patients receiving immunosuppression had more severe proteinuria and higher factor Ba. After 6 months, eGFR declined and proteinuria persisted in patients without immunosuppression. In contrast, patients who received immunosuppression exhibited decreased plasma levels of C5a, factor Ba, and Gd-IgA1 as early as 1 month after treatment. Proteinuria decreased and renal function also remained stable 6 months after immunosuppression.ConclusionsOur results indicate a close relationship between alternative complement pathway activation, Gd-IgA1 concentration and clinical severity of IgAN. Level of complement factor B may be a potential marker for disease activity and therapeutic target in IgAN patients.