Biomarkers Of Disease Severity Research Articles

Acute Disseminated Encephalomyelitis (ADEM) following viral infections: Investigating triggers, immune response and management

ADEM is diagnosed as an acute disseminated demyelinating disease of the CNS. It is normally initiated by viral infections. The objective of the current research was to elucidate the etiology, immunologic characteristics and management of ADEM in 430 subjects in Hayatabad Medical Complex, Peshawar. Of the viral causes the most commonly identified were influenza, 25%; measles, 20%; and varicella, 18%. Perhaps this may show how distribution of the infective agents common in this region may explain the occurrence of ADEM. They have similarly given out high cytokine concentration particularly IL-6 and TNF-α and similar to past findings they might not only be biomarkers of disease severity but may also be a site of immunomodulation. As for the reaction to the treatment the favorable responses are 80% of the times on corticosteroids and the IVIG and plasmapheresis are great for severe cases or if the prior one failed. Datalocalized at six months follow-up, the majority of the patients had positively improved in seventy percent with the other ten percent patients’ symptoms nearly dropped down. Therefore, the present research suggests that diagnosis of ADEM should be done early and patients ought to be put on working on formulation of tailor made treatment plans that might improve prognosis of ADEM. Findings regarding genetic profile identifying high risk patients who must be prescribed special medicine are still lacking. Therefore, this study will therefore complement information on Immune defenses and therapeutic approaches in ADEM in a region of the world where viral diseases are common.

Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap.

Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS. In this retrospective study, we collected 3D T1-weighted brain MRI scans of PwMS to build (1) a cross-sectional multicentric cohort for age and disease duration (DD) modeling and (2) a longitudinal single-center cohort of patients with early MS as a clinical use case. We trained and evaluated a 3D DenseNet architecture to predict DD from minimally preprocessed images while age predictions were obtained with the DeepBrainNet model. The brain-predicted DD gap (the difference between predicted and actual duration) was proposed as a DD-adjusted global measure of MS-specific brain damage. Model predictions were scrutinized to assess the influence of lesions and brain volumes while the DD gap was biologically and clinically validated within a linear model framework assessing its relationship with BAG and physical disability measured with the Expanded Disability Status Scale (EDSS). We gathered MRI scans of 4,392 PwMS (69.7% female, age: 42.8 ± 10.6 years, DD: 11.4 ± 9.3 years) from 15 centers while the early MS cohort included 749 sessions from 252 patients (64.7% female, age: 34.5 ± 8.3 years, DD: 0.7 ± 1.2 years). Our model predicted DD better than chance (mean absolute error = 5.63 years, R2 = 0.34) and was nearly orthogonal to the brain-age model (correlation between DD and BAGs: r = 0.06 [0.00-0.13], p = 0.07). Predictions were influenced by distributed variations in brain volume and, unlike brain-predicted age, were sensitive to MS lesions (difference between unfilled and filled scans: 0.55 years [0.51-0.59], p < 0.001). DD gap significantly explained EDSS changes (B = 0.060 [0.038-0.082], p < 0.001), adding to BAG (ΔR2 = 0.012, p < 0.001). Longitudinally, increasing DD gap was associated with greater annualized EDSS change (r = 0.50 [0.39-0.60], p < 0.001), with an incremental contribution in explaining disability worsening compared with changes in BAG alone (ΔR2 = 0.064, p < 0.001). The brain-predicted DD gap is sensitive to MS-related lesions and brain atrophy, adds to the brain-age paradigm in explaining physical disability both cross-sectionally and longitudinally, and may be used as an MS-specific biomarker of disease severity and progression.

Hyaluronan in COVID-19: a matrix for understanding lung disease

ABSTRACT The polysaccharide hyaluronan (HA) is an important component of lung extracellular matrix that increases following infection with influenza or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hellman et al. (U. Hellman, E. Rosendal, J. Lehrstrand, J. Henriksson, et al., mBio 15:e01303-24, https://doi.org/10.1128/mbio.01303-24 ) show that fragmented HA accumulates in the lungs of coronavirus disease 2019 (COVID-19) patients, with systemic levels of HA being associated with reduced lung function 3–6 months after infection. This study provides novel insights into HA’s role in COVID-19 pathology and its potential utility as a biomarker for disease severity. However, much remains to be understood about the lung HA matrix in COVID-19 and how it compares to other lung conditions. In particular, the role of HA-binding proteins in organizing HA into a crosslinked network is yet to be fully determined at a molecular level. This knowledge is crucial in understanding the inter-relationships between the structure of the HA matrix and the regulation of the immune response, and thus our ability to target HA therapeutically for improved outcomes in COVID-19.

In Silico Analysis of Probiotic Bacteria Changes Across COVID-19 Severity Stages.

The gut microbiota plays a crucial role in modulating the immune response during COVID-19, with several studies reporting significant alterations in specific bacterial genera, including Akkermansia, Bacteroides, Bifidobacterium, Faecalibacterium, Lactobacillus, Oscillospira, and Ruminococcus. These genera are symbionts of the gut microbiota and contribute to host health. However, comparing results across studies is challenging due to differences in analysis methods and reference databases. We screened 16S rRNA raw datasets available in public databases on COVID-19, focusing on the V3-V4 region of the bacterial genome. In total, seven studies were included. All samples underwent the same bioinformatics pipeline, evaluating the differential abundance of these seven bacterial genera at each level of severity. The reanalysis identified significant changes in differential abundance. Bifidobacterium emerged as a potential biomarker of disease severity and a therapeutic target. Bacteroides presented a complex pattern, possibly related to disease-associated inflammation or opportunistic pathogen growth. Lactobacillus showed significant changes in abundance across the COVID-19 stages. On the other hand, Akkermansia and Faecalibacterium did not show significant differences, while Oscillospira and Ruminococcus produced statistically significant results but with limited relevance to COVID-19 severity. Our findings reveal new insights into the differential abundance of key bacterial genera in COVID-19, particularly Bifidobacterium and Bacteroides.

Neutrophil-to-lymphocyte ratio (NLR) at diagnosis in essential thrombocythemia: A new promising predictor of thrombotic events.

Myeloproliferative neoplasms represent a heterogeneous group of acquired hematopoietic stem cell diseases in which chronic inflammation is essential for both clonal evolution and thrombotic complications. The neutrophil-to-lymphocyte ratio (NLR), reflecting the imbalance between systemic inflammation and immunity, is emerging as a prognostic biomarker in several diseases, including hematological ones. A total of 473 patients with essential thrombocythemia (ET), the relationship between NLR value at diagnosis and the risk of thrombotic events in the follow-up, in addition to conventional clinical and biological variables, were retrospectively analyzed. A total of 78 thrombotic events were reported for an incidence rate of 1.8 × 100 patients/year. In multivariate analysis, NLR value≥4 at diagnosis was associated with higher cumulative thrombotic risk (hazard ratio [HR], 2.05; 95% CI, 1.29-2.28; p=.0001) as well International Prognostic Score for Thrombosis in Essential Thrombosis score intermediate-high (HR, 2.69; 95% CI, 1.27-5.72; p=.01) and diabetes (HR, 2.49; 95% CI, 1.23-3.05; p=.010). Concerning arterial thrombotic events, in multivariate analysis, NLR value at diagnosis ≥4 was predictive for thrombosis (HR, 2.13; 95% CI, 1.31-4.04; p=.001 as well diabetes (HR, 2.44; 95% CI, 1.05-5.68; p=.04) and hypertension (HR, 2.46; 95% CI, 1.05-5.68; p=.01). About venous thrombotic events, NLR value≥5 was a marker predictive for venous thrombosis (HR, 2.99; 95% CI, 2.45-6.48; p=.01) as well age >60 years old (HR, 2.26; 95% CI, 1.0-5.10; p=.05). NLR value is a simple, cost-effective, and easy-to-obtain inflammatory marker that can predict a diagnosis the risk of thrombosis in ET. Our results suggest that NLR value could be integrated into conventional cardiovascular risk scores, to better classify high-risk patients who are candidates for cytoreductive therapy. Further larger and prospective studies are warranted.

Sensory artificial cilia for in situ monitoring of airway physiological properties

Continuously monitoring human airway conditions is crucial for timely interventions, especially when airway stents are implanted to alleviate central airway obstruction in lung cancer and other diseases. Mucus conditions, in particular, are important biomarkers for indicating inflammation and stent patency but remain challenging to monitor. Current methods, reliant on computational tomography imaging and bronchoscope inspection, pose risks due to radiation and lack the ability to provide continuous real-time feedback outside of hospitals. Inspired by the sensing ability of biological cilia, we report wireless sensing mechanisms in sensory artificial cilia for detecting mucus conditions, including viscosity and layer thickness, which are crucial biomarkers for disease severity. The sensing mechanism for mucus viscosity leverages external magnetic fields to actuate a magnetic artificial cilium and sense its shape using a flexible strain-gauge. Additionally, we report an artificial cilium with capacitance sensing for mucus layer thickness, offering unique self-calibration, adjustable sensitivity, and range, all enabled by external magnetic fields. To enable prolonged and wireless data access, we integrate Bluetooth Low Energy communication and onboard power, along with a wearable magnetic actuation system for sensor activation. We validate our method by deploying the sensor independently or in conjunction with an airway stent within a trachea phantom and sheep trachea ex vivo. The proposed sensing mechanisms and devices pave the way for real-time monitoring of mucus conditions, facilitating early disease detection and providing stent patency alerts, thereby allowing timely interventions and personalized care.

Prolactin Role in COVID-19 and Its Association with the Underlying Inflammatory Response.

The COVID-19 pandemic has prompted interest in identifying reliable biomarkers to predict disease severity and guide clinical decisions. Prolactin (PRL), a hormone traditionally associated with lactation, has gained attention for its role in immune modulation. This study aimed to assess PRL as a biomarker for disease severity in COVID-19. A prospective cohort of 142 patients with moderate to severe COVID-19, defined as a WHO-CPS 5 or 6, was recruited from the University General Hospital of Patras. Baseline PRL levels were measured using an electrochemiluminescence immunoassay, and serum cytokines, including IL-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF-α, were quantified through flow cytometry. Clinical outcomes, including mortality and the need for invasive mechanical ventilation (IMV), were recorded. Results indicated that PRL levels were significantly higher in female patients (12.95 ng/mL vs. 9.40 ng/mL, p < 0.001) but they did not correlate with key severity indices such as CCI, SOFA score upon admission or inflammatory markers. No significant associations between baseline PRL levels, cytokine concentrations, and clinical outcomes in COVID-19 were noted. Our findings suggest that PRL may lack prognostic reliability for disease severity compared to more established predictive markers and that its role in the immune response remains uncertain.

A microarray-based IgE-molecular mimicry index (IgE-MMI): A biomarker for disease severity, clinical phenotypes, and therapeutic response in atopic dermatitis?

The role of autoimmune IgE responses in atopic dermatitis (AD) is highly debated. While IgE targeting self-proteins has been extensively studied, IgE responses induced by human-homologous exogenous molecular allergens (HEMAs) remains less understood. To investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to dupilumab. We enrolled 3325 participants with a history of allergic diseases, including 577 (17.3%) diagnosed with AD. Serum IgE antibodies against 183 exogenous allergenic molecules were measured using the IgE microarray (Allergy Explorer-ALEX-2®, MADX, Vienna). Based on international classification criteria, participants were stratified by AD severity and clinical phenotypes. For each patient, we developed an 'IgE molecular-mimicry index' (IgE-MMI), calculated from IgE reactivity to a panel of five HEMA protein families: arginine kinase, enolase (ENO), cyclophilin (CYP), lipocalin, and MnSOD. Logistic regression was employed to assess the association between IgE to HEMAs or IgE-MMI and AD, its severity, and response to dupilumab. IgE sensitization to most HEMAs (32/48, 67%), but only to a small fraction of non-HEMAs (3/135, 2.2%), was significantly more common in patients with severe AD compared to other patient groups. The IgE-MMI was positive in 295/2748 (10.7%) of allergic patients without AD, and in 58/283 (20%), 52/134 (39%), and 86/160 (54%) of patients with remitting, moderate, or severe AD, respectively. It was strongly associated with specific phenotypes, such as flexural dermatitis (OR 8.4, 95% CI: 6.3-11.2), head and neck dermatitis (OR: 16.5, 95% CI: 7.4-37.2), and generalized eczema (OR: 8.6, 95% CI: 4.9-15.6). Poor response to dupilumab was associated with IgE antibodies to ENO (OR: 22.7, 95% CI: 1.7-302.9), but inversely associated with IgE antibodies to MnSOD (OR: 0.1, 95% CI: 0.02-0.8) and NPC-2 from dust mites (OR: 0.1, 95% CI: 0.01-0.9). IgE microarrays are useful for broadly assessing IgE to HEMAs in allergic patients. IgE reactivity to HEMAs and a positive IgE-MMI may serve as valuable biomarkers for severe AD, its clinical phenotypes, and the response to dupilumab.

Diagnostic Potential of NEAT1, hsa-let-7a-5p, and miR-506-3p in Early-stage Parkinson's Disease.

Parkinson's disease (PD) is a multifaceted disease that is influenced by both genetic and environmental parameters. Non-coding RNAs have been shown to be ideal biomarkers for several diseases, including PD. This study was conducted to evaluate the expression levels of NEAT1, hsa-let-7a-5p, and miR-506-3p in individuals with PD to assess their efficacy for early-stage PD diagnosis. Twenty-four patients with PD and 29 healthy individuals participated in this study. The IntaRNA tool was used to predict potential base pairings between NEAT1 and let-7a-5p, and NEAT1 and miR-506-3p. RT-qPCR was employed to measure the relative expression of tyrosine hydroxylase (TH), as well as nuclear enriched abundant transcript 1 (NEAT1), hsa-let-7a-5p, and miR-506-3p levels in both groups. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnostic value. The PD group exhibited significantly elevated NEAT1 expression levels compared to the healthy control group. While the PD group exhibited an insignificant decreased TH expression level relative to the healthy group. Furthermore, the levels of hsa-let-7a-5p and miR-506-3p expression were seen to be decreased in patients with PD in comparison to the control group. Integration of NEAT1, hsa-let-7a-5p, and miR-506-3p levels significantly enhanced diagnostic capabilities and increased the AUC to 0.9501 (95% confidence interval: 0.8978-1.000, p < .0001). The elevated NEAT1 expression and the decreased expression of hsalet- 7a-5p and miR-506-3p in PD patients indicate that these factors might contribute to the disease's pathogenesis. Combining the ROC curves of NEAT1 and hsa-let-7a-5p with miR-506-3p showed improved sensitivity and specificity, facilitating more accurate PD diagnosis. More importantly, they may contribute as promising non-invasive biomarkers for PD diagnosis.

At-home wearable-based monitoring predicts clinical measures and biological biomarkers of disease severity in Friedreich’s Ataxia

BackgroundFriedreich ataxia (FRDA) results in progressive impairment in gait, upper extremity coordination, and speech. Currently, these symptoms are assessed through expert examination at clinical visits. Such in-clinic assessments are time-consuming, subjective, of limited sensitivity, and provide only a limited perspective of the daily disability of patients.MethodsIn this study, we recruited 39 FRDA patients and remotely monitored their physical activity and upper extremity function using a set of wearable sensors for 7 consecutive days. We compared the sensor-derived metrics of lower and upper extremity function as measured during activities of daily living with FRDA clinical measures (e.g., mFARS and FA-ADL) and biological biomarkers of disease severity (guanine-adenine-adenine (GAA) and frataxin (FXN) levels), using Spearman correlation analyses.ResultsThe results show significant correlations with moderate to high effect sizes between multiple sensor-derived metrics and the FRDA clinical and biological outcomes. In addition, we develop multiple machine learning-based models to predict disease severity in FRDA using demographic, biological, and sensor-derived metrics. When sensor-derived metrics are included, the model performance enhances 1.5-fold and 2-fold in terms of explained variance, R², for predicting FRDA clinical measures and biological biomarkers of disease severity, respectively.ConclusionsOur results establish the initial clinical validity of using wearable sensors in assessing disease severity and monitoring motor dysfunction in FRDA.

Prognostic value of the right coronary venous anatomy in patients undergoing cardiac resynchronization therapy

Abstract Background The size and distribution of the coronary veins (CV) reflect both intracavitary pressure and myocardial blood flow, and therefore, in patients with cardiomyopathy, CV anatomy could potentially become a biomarker of disease severity. While the left coronary veins have been well described, there are few descriptions of the right CV system. Purpose Given these considerations, the aim of the study was to evaluate the anatomy of the right CV system and its potential prognostic significance in patients with advanced cardiomyopathy. Methods We analyzed CV angiograms from 121 patients (age 67±14 years) undergoing cardiac resynchronization therapy (CRT). The right ventricular (RV) veins were seen to fill during the injection of contrast through multiple connections with the left sided venous system. Patients were followed for a median of 43 [IQR 3-73] months, during which 12 patients expired. Results Anterior cardiac veins (ACV), which overlay the RV wall were observed in 85 (70%) patients and had a maximum ostial diameter of 2.04±0.8 mm. Multiple ACVs were seen in 62 patients. These veins were observed to empty directly into the venous sinus of right atrium (VSRA), into the RV, the right atrium (RA), or into the small cardiac vein (SCV) in 68, 9, 5, and 3 patients respectively. The right marginal vein (RMV) was visualized in 21 (17%) patients, had a diameter of 2.3±1.2 mm, and ran a course along the right border of the RV, emptying directly into RV, RA or into VSRA in 9, 4 and 8 patients respectively. The VSRA present in 91 (75%) patients, coursed parallel to the right coronary sulcus, collecting blood from the ACV’s and RMV’s and drained into the RA (Figure A); in 7 patients, 2 VSRA ostia were noted. VSRA lengths and diameters varied (11-119 mm, mean 41±25 mm) and (1.2-6.9mm, mean 2.7±1.2mm) respectively. The VSRA lengths correlated significantly with RV fractional area change, RV systolic pressure, tricuspid regurgitation severity evaluated by echocardiography, and P wave amplitude in ECG lead II (r=-0.65; p=0.041, r=0.88; p=0.019, r=0.52; p=0.030, and r=0.79; p=0.031 respectively). The VSRA diameters, which were significantly larger in patients with obstructive sleep apnea (3.6±1.5 vs. 2.3±1.2mm; p=0.021) correlated significantly with RV systolic pressure, and tricuspid regurgitation severity by echocardiography (r=0.77; p=0.009, and r=0.63; p=0.006 respectively). Patients who expired during follow-up had a significantly longer VSRA than patients who remained alive (Figure B). The VSRA length, RV fractional area change, and baseline QRS duration independently predicted survival in a Cox multivariate model that also included age and left ventricular ejection fraction. Conclusions RV venous system demonstrates a highly variable anatomy that has not been previously well described. The size of the VSRA correlated with parameters of RV function and predicted survival in patients undergoing CRT.Figure

Evaluation of aortic inflammation in marfan syndrome patients with 18-fluorodeoxyglucose positron emission and computed tomography

Abstract Background The role of inflammation in Marfan Syndrome (MS) has been well studied in current research. These studies have investigated the role of serum Interleukin 6 (IL-6), Transforming Growth Factor-b (TGF-b) and Macrophage Colony Stimulating Factor (MCSF) as biomarkers of disease severity and progression. Surgical repair is the recommended treatment of aortic aneurysms when aortic diameter reaches the indication threshold. It has been observed however that dissection may occur even before this threshold is reached. 18-fluorodeoxyglucose (18 F-FDG) positron emission tomography / computed tomography (PET/CT) is the gold standard imaging modality to noninvasively assess vascular inflammation. Purpose Our aim was to investigate whether MS patients have increased aortic wall inflammation as assessed by 18F-FDG PET/CT, and the relationship between aortic wall inflammation with serum levels of IL-6, TGF-b and MCSF. Methods The study population consisted of fifteen MS patients and seventeen sex and age matched controls. In all subjects, serum levels of circulating IL-6, TGF-b and MCSF were measured. In PET/CT, the arterial target-to-background ratio (TBR) was calculated for aortic root (AR), ascending aorta(As), aortic arch (AA) and descending aorta (DA). Also, all patients were assessed with transthoracic echocardiography where the diameters of AR, As, AA, and DA were estimated at baseline and were reexamined at the end of the follow up period. Results TBR for MS vs. controls was 2.17±0.75 vs 2.01±0.36, p=0.75 at AR; 2.15±0.67 vs 1.84±0.35, p=0.040 at As; 2.16±0.64 vs 1.70±0.25, p=0.03 at AA and 1.97±0.52 vs 1.83±0.42, p=0.23 at DA respectively. Additionally, Marfan patients had increased levels of serum biomarkers. However, this difference was statistically significant (SS) only for IL-6 serum levels; 2.17±0.46 vs 1.08±0.12 p=0.011 and IL-6 was SS associated with AR TBR (rho=0.572, p=0.033), As TBR (rho=0.604, p=0.022) and DA TBR (rho=0.714, p=0.004). Two of our patients were operated due to severe dilatation of the aortic root and the surgical specimens showed aortic wall inflammation of moderate severity along with fibrosis. Conclusion MS patients have increased of aortic wall inflammation as assessed by 18F-FDG PET/CT, a finding that highlights the role of inflammation in the pathway of disturbed TGF signaling. Further research is needed to determine its prognostic role and value in identifying patients with an indication for early intervention.

CLINICAL AND DIAGNOSTIC CRITERIALS OF LIVER FIBROSIS FORMATION IN PATIENTS WITH CHRONIC VIRAL HEPATITIS C WITH EXTRAHEPATIVE MANIFESTATIONS

Background: Chronic viral hepatitis C (CVHC) is often associated with various extrahepatic manifestations, which may complicate the disease's progression. Specific Background: Cryoglobulinemia, characterized by the presence of cryoglobulins in the blood, has been implicated in the exacerbation of liver conditions, yet its role in CVHC remains inadequately explored. Knowledge Gap: Despite existing knowledge of the relationship between cryoglobulinemia and liver disease, the specific impact of cryoglobulinemia on the severity of liver fibrosis and associated extrahepatic manifestations in CVHC patients requires further elucidation. Aims: This study aims to investigate the prevalence of extrahepatic manifestations and the extent of liver fibrosis in patients with CVHC who also present with cryoglobulinemia, thereby determining the clinical implications of cryoglobulin presence. Results: Our findings indicate that patients with cryoglobulinemia demonstrate a significantly higher prevalence of extrahepatic manifestations and advanced stages of liver fibrosis compared to those without cryoglobulinemia. Novelty: This research contributes novel insights into the aggravating role of cryoglobulins in the clinical course of CVHC, highlighting their potential as biomarkers for disease severity. Implications: These results underscore the need for enhanced clinical monitoring and tailored therapeutic approaches for CVHC patients with cryoglobulinemia, as their condition may predict a more severe disease trajectory and necessitate more aggressive management strategies.

CXCL13/CXCR5 axis facilitates TFH expansion and correlates with disease severity in adults with immune thrombocytopenia

BackgroundImmune thrombocytopenia (ITP) is an autoimmune bleeding disorder defined by a diminished platelet count. ITP pathogenesis involves intricate changes to both cellular and humoral immunity. The pivotal roles of follicular helper T (TFH) cells in the maturations of B cells and the production of antibodies are well-established. However, the specific role of TFH to the immunopathogenesis of ITP remain incompletely understood. This study aimed to clarify the association of CXCL13/CXCR5 axis with TFH in adults with ITP. MethodsA total of 97 ITP patients and 41 healthy controls were enrolled. CD4+CXCR5+ TFH, CD4+CXCR5+PD-1+ TFH, CD4+CXCR5+Foxp3+ follicular regulatory T cells (TFR), and desialylated platelets in peripheral blood were measured by flow cytometry. Plasma cytokines were assessed by enzyme-linked immunosorbent assay. CD4+ T cells cocultured with chemokine CXCL13 in vitro was performed for the measurement of TFH proliferation. Intracellular production of reactive oxygen species (ROS) was examined by dichlorodihydrofluorescein diacetate (DCFH-DA) probe staining. ResultsWe observed a significant increase in circulating TFH and a marked decrease in circulating TFR in the entire ITP cohort. The ratio of TFH/TFR was elevated, accompanied by heightened levels of platelet desialylation, cytokines BAFF, HMGB1, and IL-21, while levels of IL-10 were downregulated in adults with ITP. Notably, patients with ITP exhibiting platelet count below 50 × 109/L had dramatically elevated levels in both chemokine CXCL13 and its receptor CXCR5+ TFH compared to those with platelet count above 100 × 109/L. High frequencies of TFH correlated with poor therapeutic response. Furthermore, in vitro CD4+ T cell proliferation assay demonstrated a CXCL13 dose-dependent increase in the frequencies in both CD4+CXCR5+ TFH and CD4+CXCR5+PD-1+ TFH from ITP patients. Intriguingly, DCFH-DA assay illustrated a significant enhancement in intracellular ROS generation in CXCR5+ T cell subsets, especially in CD4+CXCR5+PD-1+ TFH from 4 patients with ITP. ConclusionsThese results underscore the pivotal role of CXCL13/CXCR5 axis-drived TFH expansion in the pathogenesis of ITP, providing a potential disease severity biomarker.

Estimation of miRNA-183 expression and TGF-β level in Chronic Myeloid Leukemia

Background: MicroRNA-183 and Transforming Growth Factor Beta (TGF-β) have emerged as significant players in the pathophysiology of Chronic Myeloid Leukemia (CML). Research indicates that miRNA-183 may play a role in the regulation of cell proliferation and apoptosis in CML cells, potentially influencing disease progression and response to therapy. Elevated levels of miRNA-183 have been associated with poor prognosis, suggesting it could serve as a biomarker for disease severity. Objective: In this study, we aimed to analyze the expression of miR-183 and TGF- β level and investigate the relationship between miR-183 and level of TGF- β in CML patients. Material and Methods: The study has been carried out on 60 Iraqi patients (37 males and 23 females at age range 17 - 69 year) with chronic myeloid leukemia at chronic phase, who are referred to the National Center of Hematology/ Mustansiriyah University, Baghdad during the period from January to November 2023. Twenty of them are newly diagnosed (T0), and the other 40 patients are under treatment with TKIs (T+), Thirty age and gender-matched healthy subjects were enrolled to act as control group. TGF-β level estimates by ELISA while micrRNA-183 detection using RT- PCR. Conclusion: The elevated levels of TGF-β and miRNA-183 in CML patients, coupled with their positive correlation.

Serum interleukin-10 level is increased and correlated positively with disease severity in patients with dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease with a linear deposit of autoantibodies at the epidermal basement membrane zone. It was reported that diabetes patients who took a dipeptidyl peptidase-4 inhibitor (DPP4i), an oral antidiabetic drug, had an increased incidence of BP. However, data on DPP4i-related BP are limited. In our study, we measured serum levels of various cytokines using LEGENDplex and assessed correlations of these serum levels with clinical severity and laboratory data. Serum samples obtained from BP patients who visited our hospital from June 2016 to February 2023 were collected in this study. Patients' background, characteristics, and clinical data were retrospectively collected from their charts. Serum samples from 27 patients with DPP4i-unrelated BP, 17 patients with DPP4i-related BP, and 13 healthy controls were analyzed. Patients with DPP4i-related BP had lower score of Bullous Pemphigoid Disease Area Index (BPDAI)-erythema/urticaria, lower number of circulating eosinophils, and lower titer of anti-BP180 antibody than patients with DPP4i-unrelated BP. The serum interleukin (IL)-6 level was significantly higher in patients with DPP4i-related BP than in healthy controls (P = 0.0037). The serum IL-10 level was significantly higher in patients with DPP4i-related BP than in patients with DPP4i-unrelated BP and in healthy controls (P = 0.0006, P = 0.0448), and was positively correlated with the BPDAI-blister/erosions score (r = 0.757, P = 0.001), BPDAI-erythema/urticaria score (r = 0.616, P = 0.013), and BPDAI-total score (r = 0.833, P < 0.001) in patients with DPP4i-related BP. In conclusion, patients with DPP4i-related BP had increased serum levels of IL-6 and IL-10 compared with healthy controls and positive correlations between the serum IL-10 level and BPDAI scores reflecting clinical severity, indicating that the serum IL-10 level is a potential objective biomarker of disease severity in patients with DPP4i-related BP.

CRP, PCT, and D-dimer as Biomarkers for Disease Severity in COVID-19 Patients: A Retrospective Study in Kinshasa, Democratic Republic of Congo

Introduction: The COVID-19 pandemic has had a significant impact on global health, resulting in more than 6 million reported deaths worldwide as of April 2023. This study aimed to investigate the potential of C-reactive protein (CRP), procalcitonin (PCT), and D-dimer as biomarkers for assessing disease severity in COVID-19 patients in Kinshasa, Democratic Republic of Congo Methods:A retrospective examination was conducted involving 339 COVID-19 patients admitted to Kinshasa hospitals between January 2021 and March 2022. CRP, PCT, and D-dimer levels were measured in all patients and compared between those with severe and non-severe illnesses. Results: Our findings revealed significantly higher CRP, PCT, and D-dimer levels in severe cases compared to non-severe cases. Specifically, the median CRP level was 120.6 mg/L in severe cases, 47.3 mg/L in mild cases, and 13.5 mg/L in moderate cases. The median PCT levels were 0.26 ng/mL in severe cases, 0.08 ng/ mL in mild cases, and 0.07 ng/L in moderate cases. Additionally, the median D-dimer level was 1836.9 µg/L in severe cases and 597.6 µg/L in mild cases, with a value of 481.1 µg/L in moderate cases. System learning techniques were also employed to predict disease severity based on these biomarkers, achieving high accuracy. Conclusion: Our findings suggest that CRP, PCT, and D-dimer serve as valuable biomarkers for identifying severe COVID-19 cases in Kinshasa. Furthermore, the application of machine learning methods can yield accurate predictions of disease severity based on these biomarkers. These biomarkers hold the potential to assist clinicians in informed decision-making regarding patient management and contribute to improved clinical outcomes for COVID-19 patients.

Neutrophil dynamics in pulmonary fibrosis: pathophysiological and therapeutic perspectives.

The shared pathobiological mechanisms driving progressive fibrosis in interstitial lung diseases (ILDs) remain unclear. Neutrophils, the most common immune cells in the human body, contain an extensive array of proteinases that are important for cell function, including tissue repair and remodelling. Increasing observational studies have reported elevated neutrophil counts in the respiratory tract and circulation of patients with ILD and suggest a role as a biomarker of disease severity. Neutrophils and their contents (including the formation of neutrophil extracellular traps (NETs)) are present in fibrotic lung tissue. Proteinases and NETs may drive fibrogenesis in animal and in vitro models and may impact transforming growth factor-β1 activation. However, the effect of neutrophil action, whether reparative or pathologically destructive to the delicate lung architecture, has yet to be determined. This review aims to summarise the current literature surrounding the potential role of the neutrophil as a biomarker and contributor to the pathogenesis of ILD. There is currently a paucity of treatment options in ILD driven by the knowledge gap underlying the overall disease mechanisms. This review concludes that neutrophils warrant further evaluation as manipulation of recruitment and function could provide a novel and much needed therapeutic strategy.

Evaluation of Selenium Concentrations in Patients with Crohn's Disease and Ulcerative Colitis.

In this study, serum selenium levels in patients with Crohn's disease (CD) and ulcerative colitis (UC) were evaluated to identify potential predictive markers of disease activity. Conducted in 100 inflammatory bowel disease (IBD) patients (54 CD, 46 UC) and 100 healthy controls, this research provides novel insights through focusing on the regional selenium status of people with IBD in the Polish population, a demographic with limited existing data. Selenium concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). Significantly lower levels of selenium were observed in CD (64.79 µg/L ± 12.15 µg/L) and UC (68.61 µg/L ± 11.43 µg/L) patients when compared with the controls (90.52 ± 12.00 µg/L, p < 0.0001). Regression analysis identified leukocyte and erythrocyte counts and bilirubin as significant predictors of selenium levels in UC patients, while no significant predictors were found for CD. The findings suggest that selenium deficiency is linked to IBD and may serve as a non-invasive biomarker for disease severity, particularly in UC. This practical approach offers a potential alternative to invasive procedures such as endoscopy for monitoring disease progression. However, further research is needed to confirm these findings in larger populations and explore the therapeutic role of selenium supplementation in IBD management.

Sulfated Bile Acids in Serum as Potential Biomarkers of Disease Severity and Mortality in COVID-19.

The fight against coronavirus disease 2019 (COVID-19) continues. Since the pandemic's onset, several biomarkers have been proposed to assess the diagnosis and prognosis of this disease. This research aimed to identify potential disease severity biomarkers in serum samples of patients with COVID-19 during the disease course. Data were collected using untargeted and targeted mass spectrometry methods. The results were interpreted by performing univariate and multivariate analyses. Important metabolite classes were identified by qualitative untargeted metabolomics in 15 serum samples from survivors of COVID-19. Quantitative targeted metabolomics on a larger patient cohort including 15 non-survivors confirmed serum 3-sulfate bile acids (i.e. GLCA-3S) were significantly increased in non-survivors compared to survivors during the early disease stage (p-value < 0.0001). Notably, it was associated with a higher risk of mortality (odds ratio of 26). A principal component analysis showed the ability to discriminate between survivors and non-survivors using the BA concentrations. Furthermore, increased BA-S is highly correlated with known parameters altered in severe clinical conditions.