Chronic Immune-mediated Disease Research Articles

Histone and Histone Acetylation-Related Alterations of Gene Expression in Uninvolved Psoriatic Skin and Their Effects on Cell Proliferation, Differentiation, and Immune Responses.

Psoriasis is a chronic immune-mediated skin disease in which the symptom-free, uninvolved skin carries alterations in gene expression, serving as a basis for lesion formation. Histones and histone acetylation-related processes are key regulators of gene expression, controlling cell proliferation and immune responses. Dysregulation of these processes is likely to play an important role in the pathogenesis of psoriasis. To gain a complete overview of these potential alterations, we performed a meta-analysis of a psoriatic uninvolved skin dataset containing differentially expressed transcripts from nearly 300 individuals and screened for histones and histone acetylation-related molecules. We identified altered expression of the replication-dependent histones HIST2H2AA3 and HIST2H4A and the replication-independent histones H2AFY, H2AFZ, and H3F3A/B. Eight histone chaperones were also identified. Among the histone acetyltransferases, ELP3 and KAT5 and members of the ATAC, NSL, and SAGA acetyltransferase complexes are affected in uninvolved skin. Histone deacetylation-related alterations were found to affect eight HDACs and members of the NCOR/SMRT, NURD, SIN3, and SHIP HDAC complexes. In this article, we discuss how histone and histone acetylation-related expression changes may affect proliferation and differentiation, as well as innate, macrophage-mediated, and T cell-mediated pro- and anti-inflammatory responses, which are known to play a central role in the development of psoriasis.

Expression of IL-7 receptor on Th1, Th17 lymphocytes in patients with psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease of the joints, spine, and entheses that can occur in patients with psoriasis. The prevalence of psoriatic arthritis is high in Russia, in recent years there has been an increase in its incidence rates. The pathogenesis of PsA is based on the activation of Th1, Th17 cells. Pro-inflammatory cytokines produced by the cells are involved in the cascade of reactions leading to the joint deformity and bone destruction. For some autoimmune diseases associated with the Th1/Th17 response, IL-7 has been found to be involved in pathogenetic mechanisms. At the same time, IL-7 is assumed to support autoreactive T lymphocytes. Effect of the cytokine on cells is provided by the binding to a specific receptor thus causing a signal transmission into the cell and inducing the processes of differentiation, proliferation, and production of cytokines. In animal models of autoimmune diseases, usage of blocking antibodies to α-chain of the IL-7 receptor (IL-7R) was shown to cause reduced inflammation in target tissues and decreased number of infiltrating T lymphocytes. Therefore, the aim of this work was to investigate the in vitro effects of IL-7 and blockade of the α-chain of the IL-7 receptor on the contents of Th1, Th17 lymphocytes and expression of IL-7 receptor subunits on these cells in normal subjects and in psoriatic arthritis. The study included nine patients with PsA in the stage of exacerbation of the underlying disease (mean age 44±6.5 years) and 6 healthy individuals (mean age 45±2.7 years). The in vitro effects of IL-7 and specific blocking monoclonal antibodies (aCD127) was evaluated in cultures of mononuclear cells from peripheral blood. Flow cytometry was used to determine the expression of IL-7 receptor subunits (CD127, CD132) and to assess cell phenotypes in peripheral blood and cultured cells. We have shown for the first time that patients with PsA have an increased number of CD127+CD132- and CD127+CD132+ cells among Th17 lymphocytes, as well as CD127+CD132-, CD127+CD132+ and CD127-CD132+ cells among Th1 lymphocytes, which suggests participation of IL-7 in maintaining these cell populations. Upon the in vitro supplement of IL-7, an increase in the Th1 cell contents and a decreased number of Th17 cells were observed, both in donors and PsA patients, and the opposite effect was observed under the conditions of IL-7R of blockade. Under the influence of IL-7, as well as with blocking antibodies, there was a significant decrease in CD127 expression on Th1, Th17 lymphocytes. However, a decrease in the number of CD127-132+ among Th1, Th17 lymphocytes occurred only following blockade with antibodies. That is, despite redistribution of Th1 and Th17 lymphocytes in culture, the cells of these populations were not activated under the IL-7 receptor blockade. The obtained data may serve as a basis for choosing the IL-7 receptor as a target in the development of targeted drugs for the treatment of PsA.

A quantitative systems pharmacology model for certolizumab pegol treatment in moderate-to-severe psoriasis.

Psoriasis is a chronic immune-mediated inflammatory systemic disease with skin manifestations characterized by erythematous, scaly, itchy and/or painful plaques resulting from hyperproliferation of keratinocytes. Certolizumab pegol [CZP], a PEGylated antigen binding fragment of a humanized monoclonal antibody against TNF-alpha, is approved for the treatment of moderate-to-severe plaque psoriasis. Patients with psoriasis present clinical and molecular variability, affecting response to treatment. Herein, we utilized an in silico approach to model the effects of CZP in a virtual population (vPop) with moderate-to-severe psoriasis. Our proof-of-concept study aims to assess the performance of our model in generating a vPop and defining CZP response variability based on patient profiles. We built a quantitative systems pharmacology (QSP) model of a clinical trial-like vPop with moderate-to-severe psoriasis treated with two dosing schemes of CZP (200 mg and 400 mg, both every two weeks for 16 weeks, starting with a loading dose of CZP 400 mg at weeks 0, 2, and 4). We applied different modelling approaches: (i) an algorithm to generate vPop according to reference population values and comorbidity frequencies in real-world populations; (ii) physiologically based pharmacokinetic (PBPK) models of CZP dosing schemes in each virtual patient; and (iii) systems biology-based models of the mechanism of action (MoA) of the drug. The combination of our different modelling approaches yielded a vPop distribution and a PBPK model that aligned with existing literature. Our systems biology and QSP models reproduced known biological and clinical activity, presenting outcomes correlating with clinical efficacy measures. We identified distinct clusters of virtual patients based on their psoriasis-related protein predicted activity when treated with CZP, which could help unravel differences in drug efficacy in diverse subpopulations. Moreover, our models revealed clusters of MoA solutions irrespective of the dosing regimen employed. Our study provided patient specific QSP models that reproduced clinical and molecular efficacy features, supporting the use of computational methods as modelling strategy to explore drug response variability. This might shed light on the differences in drug efficacy in diverse subpopulations, especially useful in complex diseases such as psoriasis, through the generation of mechanistically based hypotheses.

Herring roe oil in treatment of psoriasis - influence on immune cells and cytokine network.

Psoriasis is a chronic immune-mediated skin disease with systemic inflammation and comorbidities. Although the disease severity may vary over time, many patients suffer from mild to moderate disease. Often local treatment will be sufficient to control the symptoms, but they may have several side effects. ω-3 polyunsaturated fatty acids have shown promising results in clinical trials with mild-to-moderate psoriasis. We explored the impact of phospholipid bound docosahexaenoic acid and eicosapentaenoic acid in a 3:1 ratio on immune cells and cytokine networks in peripheral blood of patients with psoriasis. We investigated the inter-relation of plasma cytokine levels and disease severity in 58 patients, and explored the status of circulating immune cell activity in 18 patients with non-severe psoriasis before and during herring roe oil supplementation. Plasma concentration of 22 cytokines was measured by Luminex technology and circulating immune cells were analyzed by multicolor flow cytometry. CCL2 levels decreased over time, and IFN-γR1 increased, possibly related to the action of ω-3 polyunsaturated fatty acids. We observed a shift from naïve to effector CD4+ T cells and decreases of CD38 expression on CD4+ and CD8+ T cells, CD56bright NK cells and CD14+CD16- classical monocytes. These findings support the beneficial effect of herring roe oil supplementation.

Invited Session V: The eye as a window to systemic and neurodegenerative health: Early prediction of multiple sclerosis using scanning laser ophthalmoscopy (SLO) video sequence data with a Deep Learning (DL) based approach.

Multiple Sclerosis (MS) is a chronic immune-mediated inflammatory disease (IMID) of the central nervous system (CNS). Early identification of MS, especially as a screening method for at-risk individuals, is crucial to delay disease progression and improve patient outcomes by preventing future irreversible neurologic damage. In this work, we utilize well-validated tracking scanning laser ophthalmoscope (TSLO) image to predict MS compared to the unaffected controls. While traditional Machine Learning (ML) methods, such as Logistic Regression (LR), have demonstrated a strong predictive power [Mauro F. Pinto et al., 2020] in disease identification, we propose the use of a novel DL based model. Though the use of Deep Neural Network (DNN), this model can have a much higher learning capacity to capture latent features embedded in the retinal images. We hypothesize that such latent information, often hidden in ML feature engineering processes, plays an important role for the prediction of disease and can be well represented by DL models. To establish a DL based model capable of learning latent image features to provide predictive power for the presence of MS. Utilize a deep convolutional neural network to extract the retinal coding and implement a recurrent neural network to learn the temporal correlations in video sequences. Our approaches were tested using a 250-subject MS/control database collected at the UCSF. Patients with Expanded Disability Status Scale (EDSS)< 4 are compared to healthy subjects. Both raw retinal images and the frequency and spatial patterns of the eye motion are combined to construct a hybrid image, denoted as "retinal coding", and directly fed to the DL model for training and testing. Preliminary results on predictive power were measured using Area-under-Curve (AUC) of the Receiver Operating Characteristics (ROC) curve, sensitivity, and specificity, as well as an F-1 score. We observe an AUC of 0.920, sensitivity of 0.90, specificity of 0.89 and F-1 score of 0.89 using the DL model to distinguish MS from controls, which outperforms the baseline LR model by 24%. This work can be considered as a proof-of-concept concerning the possibility of identifying MS disease using a DL based approach. The results demonstrate the possibility of predicting early-stage MS and understanding disease's dynamics. Such end-to-end model could be generalizable and trained on other disease states.

Association between biological immunotherapy for psoriasis and time to incident inflammatory arthritis: limitations and opportunities

Psoriatic arthritis (PsA) is a chronic inflammatory immune-mediated disease that affects approximately 30% of psoriasis patients. In most cases, skin disease clearly precedes the musculoskeletal disease. Some studies suggest that...

Social Cognition Impairments in Association to Clinical, Cognitive, Mood, and Fatigue Features in Multiple Sclerosis: A Study Protocol.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS), characterized by the diffuse grey and white matter damage. Cognitive impairment (CI) is a frequent clinical feature in patients with MS (PwMS) that can be prevalent even in early disease stages, affecting the physical activity and active social participation of PwMS. Limited information is available regarding the influence of MS in social cognition (SC), which may occur independently from the overall neurocognitive dysfunction. In addition, the available information regarding the factors that influence SC in PwMS is limited, e.g., factors such as a patient's physical disability, different cognitive phenotypes, mood status, fatigue. Considering that SC is an important domain of CI in MS and may contribute to subjects' social participation and quality of life, we herein conceptualize and present the methodological design of a cross-sectional study in 100 PwMS of different disease subtypes. The study aims (a) to characterize SC impairment in PwMS in the Greek population and (b) to unveil the relationship between clinical symptoms, phenotypes of CI, mood status and fatigue in PwMS and the potential underlying impairment on tasks of SC.

Neutrophil-to-Lymphocyte Ratio, Neutrophil-to-Monocyte Ratio, Platelet-to-Lymphocyte Ratio, and Systemic Immune-Inflammation Index in Psoriasis Patients: Response to Treatment with Biological Drugs.

Psoriasis is a chronic immune-mediated skin disease in which systemic inflammation plays an important role in its pathogenesis. In recent years, the neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-monocyte ratio (NMR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were shown to be important indicators of inflammation. This study aimed to investigate the NLR, NMR, PLR, and SII levels in psoriasis patients treated with biological agents. Clinical and biochemical data of 209 patients who received systemic therapy for psoriasis were obtained by retrospectively reviewing their medical records. The NLR, NMR, PLR, and SII values were calculated from the hemogram values of the patients. In the third month of follow-up, the mean CRP, NLR, NMR, PLR, and SII values were significantly decreased compared with the baseline values. The SII values showed strong positive correlations with the NLR, NMR, and PLR. Adalimumab, etanercept, and infliximab, which are TNF-α blockers, were observed to be more effective on the PLR and NLR, and especially the NMR. The NLR, NMR, PLR, and SII, which are data derived from routine blood tests, can be used in the monitoring of the treatment of psoriasis, especially with TNF-α blockers.

Humanization Guide of the Spanish Society of Hospital Pharmacy for patients with inflammatory immune-mediated diseases

ObjectiveThis study reports on the results of a project conducted by the Spanish Society of Hospital Pharmacy with patients with immune-mediated inflammatory diseases, with the following objectives: to understand the experience of patients living with these diseases and the role of healthcare workers in such experience, and to identify opportunities to promote or boost humanization in hospital pharmacy units. MethodA user-centered design methodology was used, implementing exploratory and qualitative research tools. Led by a managing team made up of experts in the methodology, a variety of people participated in this project. The team comprised representatives of patients with immune-mediated inflammatory diseases, healthcare workers responsible for their care, members of the immune-mediated inflammatory disease working group of the Spanish Society of Hospital Pharmacy, and members of two patient advocacy organizations (Spanish Association of Persons with Chronic Immune-Mediated Inflammatory Diseases and the Spanish Association of Patients with Psoriasis). The research tools used included in-depth interviews, patients’ diaries, ethnographic studies, and co-creation workshops. ResultsFive initiatives were identified as best practices to be implemented: The creation of functional or comprehensive care units; shared medical records; integration of patient-reported outcomes with patient experiences; implementation of the “capacity, motivation, opportunity” pharmaceutical care model; and a closer interaction with patient advocacy organizations. Six opportunities to improve the current situation were selected as priority areas for hospital pharmacy departments: spreading knowledge about immune-mediated inflammatory diseases; promoting a multidisciplinary approach to these diseases; generating awareness on the role of hospital pharmacists; revisiting the internal organization of pharmacy departments; establishing closer relationships with patients; and seeing things from the patients’ point of view. Ten smart humanization initiatives were proposed and classified in an impact-effort matrix: “Demystifying IMID”, “IMID teen challenge”, “Patient-care academy”, “Satellite consultation”, “IMID network”, “A click away from the pharmacy”, Medicines poker”, “Patient-to-patient consultation”, “Pharma-friendly consultation”, and “Patient-centered IMID sessions”. ConclusionsThis Annex to the Spanish Society of Hospital Pharmacy’s Guidelines for the Humanization of Hospital Pharmacy Units intends to promote a humanizing culture, bringing to the fore the unique value of every single patient suffering from an immune-mediated inflammatory disease, including their family and friends and their beliefs and needs, preserving their dignity.

Inflammatory Bowel Disease as a Paradoxical Reaction to Anti-TNF-α Treatment-A Review.

TNF-α inhibitors (TNFis) have revolutionized the treatment of certain chronic immune-mediated diseases, being widely and successfully used in rheumatic inflammatory diseases, and have also proved their efficacy in the treatment of inflammatory bowel disease (IBD). However, among the side effects of these agents are the so-called paradoxical effects. They can be defined as the appearance or exacerbation of a pathological condition that usually responds to this class of drug while treating a patient for another condition. A wide range of paradoxical effects have been reported including dermatological, intestinal and ophthalmic conditions. The causal mechanism of occurrence may implicate an imbalance of cytokines, but is still not fully understood, and remains a matter of debate. These paradoxical reactions often show improvement on discontinuation of the medication or on switching to another TNFi, but in some cases it is a class effect that could lead to the withdrawal of all anti-TNF agents. Close monitoring of patients treated with TNFis is necessary in order to detect paradoxical reactions. In this study we focus on reviewing IBD occurrence as a paradoxical effect of TNFi therapy in patients with rheumatological diseases (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis).

Is the Pediatric Eosinophilic Esophagitis Symptom Score v2.0 reliable for telemedicine?

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease. Telemedicine is a healthcare technology used when a patient is separated by distance. The reliability of the Pediatric Eosinophilic Esophagitis Symptom Score, version 2.0 (PEESS v2.0) for telemedicine applications, has not been studied yet. Therefore, we aimed to evaluate the reliability of PEESS v2.0 for telemedicine. We sent a telesurvey using questionnaires via electronic telecommunication as the telemedicine method. Children with EoE and their parents were asked to complete PEESS v2.0 with the telesurvey method (unsynchronized with the physician) and attend in-person visits one week apart. Intraclass correlation (ICC), Wilcoxon, and Bland-Altman tests were used as reliability analyses. Reliability was defined as a strong agreement between the measurements in ICC ≥ 0.8 and a p-value of ≤0.05 and no statistically significant difference between the scores of the two methods in the Wilcoxon and Bland-Altman analyses, i.e. a p-value of >0.05. The total scores of children and parents were higher in in-person visits than in the telesurvey (Wilcoxon tests, p ≤ 0.05). Bland- Altman analysis showed that the mean difference in total scores between the two methods was significant for both children and parents (p ≤ 0.05). ICC levels for the children and parent scores for the entire group ranged from 0.595 to 0.763 (moderate agreement). Unsynchronized telesurvey use of PEESS v2.0 is unreliable both for children and parents. We suggest testing the reliability of chosen telemedicine methods before using them in clinical and research practice.

Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial

IgA nephropathy is a chronic immune-mediated kidney disease and a major cause of kidney failure worldwide. The gut mucosal immune system is implicated in its pathogenesis, and Nefecon is a novel, oral, targeted-release formulation of budesonide designed to act at the gut mucosal level. We present findings from the 2-year, phase 3 NefIgArd trial of Nefecon in patients with IgA nephropathy. In this phase 3, multicentre, randomised, double-blind, placebo-controlled trial, adult patients (aged ≥18 years) with primary IgA nephropathy, estimated glomerular filtration rate (eGFR) 35-90 mL/min per 1·73 m2, and persistent proteinuria (urine protein-creatinine ratio ≥0·8 g/g or proteinuria ≥1 g/24 h) despite optimised renin-angiotensin system blockade were enrolled at 132 hospital-based clinical sites in 20 countries worldwide. Patients were randomly assigned (1:1) to receive 16 mg/day oral capsules of Nefecon or matching placebo for 9 months, followed by a 15-month observational follow-up period off study drug. Randomisation via an interactive response technology system was stratified according to baseline proteinuria (<2 or ≥2 g/24 h), baseline eGFR (<60 or ≥60 mL/min per 1·73 m2), and region (Asia-Pacific, Europe, North America, or South America). Patients, investigators, and site staff were masked to treatment assignment throughout the 2-year trial. Optimised supportive care was also continued throughout the trial. The primary efficacy endpoint was time-weighted average of eGFR over 2 years. Efficacy and safety analyses were done in the full analysis set (ie, all randomly assigned patients). The trial was registered on ClinicalTrials.gov, NCT03643965, and is completed. Patients were recruited to the NefIgArd trial between Sept 5, 2018, and Jan 20, 2021, with 364 patients (182 per treatment group) randomly assigned in the full analysis set. 240 (66%) patients were men and 124 (34%) were women, and 275 (76%) identified as White. The time-weighted average of eGFR over 2 years showed a statistically significant treatment benefit with Nefecon versus placebo (difference 5·05 mL/min per 1·73 m2 [95% CI 3·24 to 7·38], p<0·0001), with a time-weighted average change of -2·47 mL/min per 1·73 m2 (95% CI -3·88 to -1·02) reported with Nefecon and -7·52 mL/min per 1·73 m2 (-8·83 to -6·18) reported with placebo. The most commonly reported treatment-emergent adverse events during treatment with Nefecon were peripheral oedema (31 [17%] patients, vs placebo, seven [4%] patients), hypertension (22 [12%] vs six [3%]), muscle spasms (22 [12%] vs seven [4%]), acne (20 [11%] vs two [1%]), and headache (19 [10%] vs 14 [8%]). No treatment-related deaths were reported. A 9-month treatment period with Nefecon provided a clinically relevant reduction in eGFR decline and a durable reduction in proteinuria versus placebo, providing support for a disease-modifying effect in patients with IgA nephropathy. Nefecon was also well tolerated, with a safety profile as expected for a locally acting oral budesonide product. Calliditas Therapeutics.

Evaluation of low level laser therapy versus topical steroids in management of symptomatic oral lichen planus by detecting the level of salivary interleukin-6

Background: Oral lichen planus (OLP) is a relatively common chronic inflammatory immune-mediated disease affecting the oral mucosa with episodes of exacerbations and remissions. The current study was aimed to compare between the therapeutic outcomes of using low level laser therapy (LLLT) and topical steroids in management of symptomatic OLP and to correlate between the salivary levels of interleukin-6 (IL-6) in in relation to the clinical scores (CS) and pain visual analogue scores (P-VAS) before and after treatment. Subjects and methods: 40 participants were included in this study and were divided into 4 groups of 10 participants each. Group (I) included ten symptomatic atrophic or erosive OLP patients and received topical steroid (triamcinolone acetonide 0.1%). Group (II) comprised also of ten patients having symptomatic OLP and managed with LLLT using 810 nm diode laser. Group (III) included ten patients with asymptomatic reticular OLP. Group (IV) included ten healthy volunteers having no oral or skin lichen planus lesions.

The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αβ) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.

Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy.

Chronic local inflammation underlies the pathogenesis of age-related macular degeneration (AMD) causing damage to the neurosensory retina. However, there is minimal research on systemic cell-mediated inflammation in AMD. Interleukin-4 (IL-4) is an immunoregulatory cytokine with an important role in modulating inflammation in chronic immune mediated disease. The purpose of this study was to: (1) investigate the role of systemic IL-4 in patients with intermediate AMD (iAMD) and in geographic atrophy (GA), an advanced form of AMD, compared to controls without AMD, and (2) determine if IL-4 levels are moderated by sex. We examined plasma levels of IL-4 in patients with iAMD, GA, and controls without AMD included in the University of Colorado AMD registry (August 2014 to June 2021). Cases and controls were defined by multimodal imaging. IL-4 was measured by multiplex immunoassay. Data were analyzed using a nonparametric rank based linear regression model fit to IL-4. There were 199 patients with iAMD, 97 patients with GA, and 139 controls, with a percentage of female patients 61%, 55%, and 66%, respectively. We demonstrated significantly higher median IL-4 levels in GA (35.3; interquartile range [IQR] = 22.8-50.5) compared to iAMD (6.1; IQR = 2.2-11.3, P < 0.01) and controls (10.7; IQR = 5.0-16.8, P < 0.01). There were no significant differences in levels of IL-4 for cases and controls when stratified by sex. These findings demonstrate a systemic immunological difference between iAMD and GA, indicating IL-4 may be a systemic biomarker for GA development. The plasma biomarker IL-4 is significantly elevated in patients with GA.

The Role of CCL24 in Systemic Sclerosis.

Systemic sclerosis (SSc) is a chronic immune-mediated disease characterized by microangiopathy, immune dysregulation, and progressive fibrosis of the skin and internal organs. Though not fully understood, the pathogenesis of SSc is dominated by microvascular injury, endothelial dysregulation, and immune response that are thought to be associated with fibroblast activation and related fibrogenesis. Among the main clinical subsets, diffuse SSc (dSSc) is a progressive form with rapid and disseminated skin thickening accompanied by internal organ fibrosis and dysfunction. Despite recent advances and multiple randomized clinical trials in early dSSc patients, an effective disease-modifying treatment for progressive skin fibrosis is still missing, and there is a crucial need to identify new targets for therapeutic intervention. Eotaxin-2 (CCL24) is a chemokine secreted by immune cells and epithelial cells, which promotes trafficking of immune cells and activation of pro-fibrotic cells through CCR3 receptor binding. Higher levels of CCL24 and CCR3 were found in the skin and sera of patients with SSc compared with healthy controls; elevated levels of CCL24 and CCR3 were associated with fibrosis and predictive of greater lung function deterioration. Growing evidence supports the potency of a CCL24-blocking antibody as an anti-inflammatory and anti-fibrotic modulating agent in multiple preclinical models that involve liver, skin, and lung inflammation and fibrosis. This review highlights the role of CCL24 in orchestrating immune, vascular, and fibrotic pathways, and the potential of CCL24 inhibition as a novel treatment for SSc.

Patient preferences in chronic immune-mediated inflammatory diseases potentially treated with biological drugs: discrete choice analysis using real-world data analysis

ABSTRACT Objectives Immune-mediated inflammatory diseases (IMIDs) represent a high burden due to their chronicity, high prevalence, and associated comorbidities. Chronic patients’ preferences must be considered in IMIDs treatment and follow-up. The objective of this study was to further understand patient’s preferences in private settings. Methods A literature review was performed to choose the most relevant criteria for patients. A D-efficient discrete choice experiment was designed to elicit preferences of adult patients with IMIDs and potential biological treatment prescription. Participants were collected from private practices (rheumatology, dermatology, and gastroenterology) from February to May 2022. Patients chose between option pairs, characterized by six health-care attributes, as well as monthly out-of-pocket drug price. Responses were analyzed through a conditional logit model. Results Eighty-seven patients answered the questionnaire. The most frequent pathologies were Rheumatoid Arthritis (31%) and Psoriatic Arthritis (26%). The most relevant criteria were choosing the preferred physician (OR 2.25 [SD0.26]); reducing time until visit with specialist (OR 1.79 [SD0.20]), access through primary care (OR 1.60 [SD0.08]), and an increase in monthly out-of-pocket price from 100€ to 300€ (OR 0.55 [SD0.06]) and to 600€ (OR 0.08 [SD0.02]). Conclusions Chronic IMIDs patients showed a preference toward a faster, personalized service, even with a trade-off in terms of out-of-pocket price

Comparative Study on Efficacy of Topical Application of Triamcinolone Acetonide and Curcumin in Management of Oral Lichen Planus

Introduction: Oral lichen planus (OLP) is a chronic inflammatory and immune mediated disease that affects the mucous membranes. OLP is cell-mediated, immune damage to basal keratinocytes that are recognized as being antigenically foreign or altered. Many treatment modalities have been tried since the time immemorial, steroids being the mainstay of the treatment, with more benefits than adversities, but now-a-days alternative/ herbal medicines are used keeping in view the chronicity of disease and long term treatment required to cure it. Curcuminoids, the major constituent of turmeric, has anti-inflammatory, antioxidant and anticancer properties. Natural / herbal product has minimal adversities so this can be more helpful for patients in the upcoming time. Aim: The study was conducted to compare the efficacy of conventional topical corticosteroid, triamcinolone acetonide 0.1% with 1% curcumin gel in OLP patient and to assess reduction in burning sensation, regression of size and ulcero-erosive appearance of lesion. Materials and Methods: An intervention study was conducted on 40 patients diagnosed with OLP which were divided into two groups. Group A was provided with Ointment 0.1% triamcinolone acetonide while Group B was provided with 1% curcuma longa extracts gel for local application on the affected regions The results were analysed using Students t-test,discrete (categorical) data were summarised in number (n) and percentage (%) and compared by chi-square (χ2) test. Groups were also compared by two factor (groups and periods) repeated measure (RM) analysis of variance (ANOVA). Results: Intragroup comparison showed statistically significant reduction in burning sensation, size and extension of lesion (p&lt;0.001) as well as erythema and ulceration (p&lt;0.001) in both the groups. In inter-group comparison, Group A showed reduction in burning sensation (97.3%), size and extension of lesion (100%), reduction in erosive pattern (94.7%) and reduction in ulcerative .......

A Study of miRNA 223 Expression and its Correlation with Disease Severity in Chronic Plaque Psoriasis.

Psoriasis is a chronic immune-mediated inflammatory disease affecting the skin and/or joints. MicroRNAs (miRNA) are single-stranded non-coding RNA molecules that bind to messenger RNA (mRNA) and regulate gene expression. Studies on peripheral blood mononuclear cells (PBMCs) in psoriatic patients showed an upregulation of miRNA 223. a) To estimate and compare the expression of miRNA 223 in cases of chronic plaque psoriasis and controls. b) To correlate the expression of miRNA 223 with the severity of chronic plaque psoriasis. This study included 80 subjects (40 with psoriasis and 40 with age- and sex-matched healthy controls) attending the dermatology OPD of a tertiary care hospital from January 2018 to June 2019. A detailed history, determination of Psoriasis Area Severity Index (PASI) score and estimation of miRNA 223 by quantitative real-time polymerase chain reaction (qRT-PCR), was done in all subjects. The expression of miRNA 223 (ΔCt) was higher in cases than in controls. The observed mean ΔCt was higher in severe (12.90 ± 0.46) than in mild (9.81 ± 1.70) and moderate (10.58 ± 1.26) psoriasis. The difference in expression of miRNA with varying severity of psoriasis was significant. The mean difference of ΔCt between mild to severe was (3.09) (P ≤ 0.001) and moderate to severe was (2.31) (P = 0.013). Among cases, the expression of miRNA 223 was higher in those exhibiting Koebner's phenomenon compared to those without Koebner's phenomenon (P = 0.0424). Expression of miRNA 223 was higher in psoriatic patients than in controls and the expression increased with the severity and activity of the disease suggesting the upregulation of miRNA 223 with the progression and activity of the disease.

Hippocampal volume in cases of relapsing remitting multiple sclerosis and its correlation with cognitive impairment

Background. Multiple sclerosis (MS) is a chronic inflammatory immune-mediated disease, distinguished by demyelination and oligodendropathy in the central nervous system. Cognitive impairment (CI) can impact patients at any stage of MS, including those with clinically isolated syndrome (CIS). Patients and methods. This is a prospective cross-sectional study which enrolled 60 patients with RRMS. They were subjected to cognitive scale assessment, routine brain MRI study and volumetric assessment of hippocampus. Results. This study found a significant positive correlation between duration of disease and Subjective memory complaints questionnaire (r=0.525, p=0.001). A significant negative correlation existed between disease duration and MMSE score (r=-0.404, p=0.001) and between disease duration and MoCA score (r=-0.310, p=0.016). No significant difference between both groups regarding the relative hippocampal volume. Mean relative right hippocampal volume is 0.0026 for cases versus 0.0027 among control group and mean relative left hippocampal volume is 0.0025 for cases versus 0.0026 among control group. Conclusion. Multiple sclerosis disease duration had an impact on cognitive state. However, hippocampal volume assessment did not predict the cognitive affection in patient with RRMS.