Extended Inflammation Parameters (EIP) as Markers of Inflammation in Systemic Sclerosis.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation, progressive vasculopathy, and fibrosis of skin and internal organs. The aim of the study was to evaluate extended inflammatory parameters (EIP) in patients with SSc in comparison to the control group of healthy subjects. Methods: A total of 28 patients with SSc and 29 healthy controls (HCs) were included in the study. The following EIP parameters were analyzed: neutrophil reactive intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), antibody-synthesizing lymphocytes (AS-LYMP), and reactive lymphocytes (RE-LYMP). Results: Patients with SSc showed significantly higher values of parameters determining neutrophil reactivity and neutrophil granularity when compared to HCs (respectively, 49.16 FI vs. 44.33 FI, p < 0.001, and 152.01 SI vs. 147.51 SI, p < 0.001). Moreover, patients with SSc had higher absolute numbers of RE-LYMP than HCs (0.69 × 103/µl vs. 0.04 × 103/µl, p < 0.001). Importantly, significant correlations between the RE-LYMP and either IL-6 (R = 0.447, p < 0.001) or ESR (R = 0.532, p < 0.001) were found among patients with SSc. Conclusions: Changes in NEUT-RI, NEUT-GI, and RE-LYMP levels positively correlate with inflammation in SSc and, thus, could potentially be used as an additional reliable inflammatory biomarker to assess inflammation in this disease.

Systemic Scleroderma-Definition, Clinical Picture and Laboratory Diagnostics.

(1) Background: Scleroderma (Sc) is a rare connective tissue disease classified as an autoimmune disorder. The pathogenesis of this disease is not fully understood. (2) Methods: This article reviews the literature on systemic scleroderma (SSc). A review of available scientific articles was conducted using the PubMed database with a time range of January 1985 to December 2021. (3) Results and Conclusions: The article is a review of information on epidemiology, criteria for diagnosis, pathogenesis, a variety of clinical pictures and the possibility of laboratory diagnostic in the diagnosis and monitoring of systemic scleroderma.

Assessment of Immune Cell Activation in Pemphigus.

(1) Background: Pemphigus is a blistering autoimmune disease of the skin and/or mucous membranes, characterised by the presence of specific autoantibodies directed against structural proteins of the human skin. Recent reports indicate that new haematological parameters, termed Extended Inflammation Parameters (EIP), can be used to assess the activation of immune cells during active inflammation. These include parameters assessing both neutrophil activation (NEUT-RI, NEUT-GI) and the number of activated lymphocytes (RE-LYMP). The aim of this study was to investigate the relationship between changes in NEUT-RI, NEUT-GI and RE-LYMP and the disease activity in patients with pemphigus. (2) Results: The study involved 32 patients with diagnosed different types of pemphigus. Neutrophil activation parameters (NEUT-RI and NEUT-GI) and lymphocytes (RE-LYMP) were significantly higher in these patients compared to the parameters in healthy participants (respectively p = 0.0127, p = 0.0011 and p = 0.0033). The increased quantity of activated lymphocytes (RE-LYMP) also correlated significantly with the extent of skin and/or mucosal lesions in patients assessed by the PDAI scale (p < 0.02). (3) Conclusions: The NEUT-RI, NEUT-GI and RE-LYMP parameters proved to be appropriate markers of inflammation severity in pemphigus, also in relation to local lesions, which was not possible with the inflammation markers (CRP, ESR) used so far on a routine basis.

Indicator of Inflammation and NETosis-Low-Density Granulocytes as a Biomarker of Autoimmune Hepatitis.

Introduction. Interest in the potential role of low-density granulocytes (LDGs) in the development of autoimmune diseases has been renewed recently. Due to their pro-inflammatory action, more and more attention is paid to the role of LDGs, including those expressing the enzyme myeloperoxidase (MPO), in the development of autoimmune hepatitis (AIH). LDGs are actively involved in the formation of neutrophil extracellular traps (NETs). This phenomenon may favour the externalization of the autoantigen and lead to damage to internal organs, including the liver. Aim. The main aim of the study was to assess the diagnostic usefulness of the LDG percentage, including the fraction showing MPO expression as markers of systemic inflammation in AIH. Materials and methods. The study included a group of 25 patients with AIH and 20 healthy volunteers. Mononuclear cells, isolated from peripheral blood, were labelled with monoclonal antibodies conjugated to the appropriate fluorochromes (CD15-FITC, CD14-PE, CD10-PE-Cy5, MPO+) and then analyzed on a Navios Flow Cytometer (Beckman Coulter). Results. Patients with AIH had a higher median percentage of LDG (1.2 vs. 0.1; p = 0.0001) and LDG expressing MPO (0.8 vs. 0.3; p = 0.0017) when compared to healthy volunteers. Moreover, the percentage of LDG was characterised by 100% of sensitivity and 55% of specificity (AUC = 0.84; p < 0.0001), while the percentage of LDG expressing MPO was 92% of sensitivity and 55% of specificity (AUC = 0.78; p = 0.0001) in the detection of AIH. Conclusions. Assessment of inflammatory markers, such as the percentage of LDG and the percentage of LDG expressing MPO, may be helpful in assessing the phenomenon of an increased systemic inflammatory response and in assessing liver fibrosis (LC, Liver cirrhosis), which is inherent in liver decompensation. Taking into account the above arguments, the assessment of the percentage of LDG, including LDG expressing MPO, may turn out to be a useful marker in the diagnosis of AIH.

The Usefulness of Extended Inflammation Parameters and Systemic Inflammatory Response Markers in the Diagnostics of Autoimmune Hepatitis.

(1) Introduction: Autoimmune hepatitis (AIH) is a chronic disease. A persistent autoimmune reaction in the liver is significantly related to the systemic inflammatory response. Extended Inflammation Parameters (EIP) can be used to assess the activation of immune cells such as activated neutrophils (NEUT-RI and NEUT-GI) and activated lymphocytes (RE-LYMP and AS-LYMP) in the phase of active inflammation. The role of the systemic inflammatory response markers should also be emphasised, especially: NLR, PLR, and RLR, which have recently been widely studied as markers in autoimmune skin diseases or liver diseases. (2) Materials and Methods: The study included 30 patients with AIH and 30 healthy volunteers. The parameters of the EIP group (RE-LYMP, AS-LYMP, NEUT-RI, NEUT-GI), calculated haematological indices Red Blood Cell Distribution Width-to-Platelet Ratio (RPR), Mean Platelet Volume-to-Platelet Ratio (MPR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Red Blood Cell Distribution Width-to-Lymphocyte Ratio (RLR), and selected blood morphological and biochemical indices were analysed. The aim of the study was to assess the usefulness of the EIP and systemic inflammatory response markers in the diagnostics of AIH. (3) Results: Compared to the controls, the patients with AIH showed significantly higher EIP values: NEUT-RI (48.05 vs. 43.30), NEUT-GI (152.65 vs. 147.40), RE-LYMP (0.07 vs. 0.03), and the inflammatory response markers: MPR (0.05 vs. 0.04), RPR (0.07 vs. 0.05), and NLR (2.81 vs. 1.42. Among the examined markers, EIP has significant diagnostic potential: NEUT-RI (AUC = 0.86), NEUT-GI (AUC = 0.80), and RE-LYMP (AUC = 0.78), and so do calculated haematological indices, i.e., MPR (AUC = 0.75), PLR (AUC = 1.00), and RLR (AUC = 1.00) Moreover, the importance of NEUT-GI (AUC = 0.89), MPR (AUC = 0.93), PLR (AUC = 0.86), RPR (AUC = 0.91), and FIB-4 (AUC = 0.83) in the detection of liver fibrosis in the course of AIH has also been proven. (4) Conclusions: EIP and systemic inflammatory response markers may turn out to be useful in detecting AIH and in looking for features of already developed liver cirrhosis in its course.

Etiopathogenesis and Diagnostic Strategies in Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) is a chronic liver disease with the incidence of 10 to 17 per 100,000 people in Europe. It affects people of any age, but most often occurs in the 40-60 age group. The clinical picture is varied, from asymptomatic to severe acute hepatitis or liver failure. The disease onset is probably associated with the impaired function of T lymphocytes, the development of molecular mimicry, intestinal dysbiosis, or infiltration with low density neutrophils, which, alongside autoantibodies (i.e., ANA, ASMA), implicate the formation of neutrophil extracellular traps (NETs), as a component of the disease process, and mediate the inappropriate immune response. AIH is characterized with an increased activity of aminotransferases, elevated concentration of serum immunoglobulin G, the presence of circulating autoantibodies and liver inflammation. The result of the histological examination of the liver and the presence of autoantibodies, although not pathognomonic, still remain a distinguishing feature. The diagnosis of AIH determines lifelong treatment in most patients. The treatment is implemented to prevent the development of cirrhosis and end-stage liver failure. This work focuses mainly on the etiopathogenesis and diagnosis of AIH.

Extended Inflammation Parameters (EIP) as Markers of Immune System Cell Activation in Psoriasis.

Psoriasis is an inflammatory, autoimmune disease that affects approximately 2% of the population. The inflammation in psoriasis can be systemic, so despite a predominantly cutaneous manifestation, it also affects the internal organs. The diagnosis and monitoring of the disease are based on the clinical picture. To assess the disorders of other organs, additional tests need to be performed. Recently, the examination of blood morphology has been enriched with modern haematological parameters, i.e., Extended Inflammation Parameters (EIP), which include RE-LYMPH (activated lymphocytes), AS-LYMPH (antibody-producing B lymphocytes), and NEUT-RI and NEUT-GI (activated neutrophils). In the study, higher values of new haematological parameters were observed in individuals with psoriasis than in healthy controls. A higher EIP value was noted in the group of individuals with plaque psoriasis than in the group of individuals with psoriatic arthritis. Implementation of these parameters into routine laboratory analysis will likely make it possible to estimate the severity of the inflammation and improve its assessment.

Teicoplanin-Modified HPLC Column as a Source of Experimental Parameters for Prediction of the Anticonvulsant Activity of 1,2,4-Triazole-3-Thiones by the Regression Models.

The cell membrane is a complex system that consists of lipids, proteins, polysaccharides, and amphiphilic phospholipids. It plays an important role in ADME processes that are responsible for the final pharmaceutical effects of xenobiotics (bioavailability, activity). To study drug-membrane interaction at the molecular level, several high-performance liquid chromatography (HPLC) membrane model systems have been proposed which are mimicking mainly its lipid character. The aim of this work was to study interactions of new synthesized antiepileptic compounds of 4-alkyl-5-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives with Chirobiotic column containing glycoprotein ligand attached to the silica matrix. The affinity of the analytes to immobilized glycoprotein ligand was examined chromatographically in reversed-phase mode. The thermodynamics of interactions between bioactive compounds and teicoplanin was studied in terms of the van't Hoff linear relationship ln k vs. 1/T in the range of 5-45 °C. Change in enthalpy (ΔH°), change in entropy (ΔS°) and change in Gibbs free energy (ΔG°) were estimated utilizing graphical extrapolation and interpolation methods. The density functional theory (DFT) approach and docking simulations were used to get the molecular interpretation and prove the obtained experimental results. Cross-correlations of chromatographic and thermodynamic parameters with non-empirical topological and quantum chemical indices suggest that the polarizability of analytes appears to be responsible for the interactions of the tested molecules with teicoplanin and, ultimately, their retention on the column. Experimental and theoretical parameters were subjected to statistical analysis using regression models. Partial least squares (PLS) regression model showed the usefulness of the experimentally measured parameter φ0 (MeOH) to discriminate between anticonvulsant active and inactive 1,2,4-triazole-3-thione derivatives. Obtained results point out the usefulness of interaction of potential anticonvulsants with glycoprotein class of compounds to anticipate their activity.