Autoimmune Inflammatory Conditions Research Articles

Epigenetic Regulation of Immune Cells in Health and Disease: A Comprehensive Review

Epigenetic regulation plays a crucial role in the development, differentiation, and function of immune cells. Mechanisms such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA interactions dynamically shape gene expression, enabling immune cells to adapt to environmental stimuli and mediate appropriate immune responses. Aberrant epigenetic regulation is implicated in a range of diseases, including autoimmune disorders, cancer, and chronic inflammatory conditions. In autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, altered DNA methylation and histone modifications contribute to immune dysregulation and tissue damage. In cancer, immune cells in the tumor microenvironment often exhibit epigenetic changes that facilitate immune evasion. Emerging therapeutic strategies targeting epigenetic pathways, including DNA methyltransferase inhibitors, histone deacetylase inhibitors, and CRISPR-based epigenome editing, offer promising approaches for treating immune-mediated diseases. This review provides a comprehensive overview of the epigenetic mechanisms governing immune cell behavior, their dysregulation in disease, and the potential of epigenetic therapies to restore immune homeostasis and improve patient outcomes. Keywords: Epigenetics, immune cells, DNA methylation, histone modifications, non-coding RNAs, autoimmune diseases, immunotherapy

Immune-Mediated Inflammatory Diseases, Dyslipidemia, and Cardiovascular Risk: A Complex Interplay.

Individuals with autoimmune inflammatory diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, are at increased risk for cardiovascular disease. While these diseases share common features of systemic inflammation, the impact of individual autoimmune inflammatory conditions on circulating lipids and lipoproteins varies by specific disease, disease activity, and the immune-suppressing medications used to treat these conditions. A common feature observed in many autoimmune inflammatory diseases is the development of a proatherogenic dyslipidemic state, characterized by dysfunctional HDLs (high-density lipoproteins) and increased oxidation of LDLs (low-density lipoproteins). Various disease-modifying antirheumatic drugs also have complex and variable effects on lipids, and it is critical to take this into consideration when evaluating lipid-related risk in individuals with immune-mediated inflammatory conditions. This review aims to critically evaluate the current understanding of the relationship between immune-mediated inflammatory diseases and dyslipidemia, the underlying mechanisms contributing to atherogenesis, and the impact of various pharmacotherapies on lipid profiles and cardiovascular risk. We also discuss the role of lipid-lowering therapies, particularly statins, in managing residual risk in this high-risk population and explore the potential of emerging therapies with complementary anti-inflammatory and lipid-lowering effects.

IVIG response in pediatric acute-onset neuropsychiatric syndrome correlates with reduction in pro-inflammatory monocytes and neuropsychiatric measures.

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterized by abrupt onset of obsessive-compulsive disorder or eating restriction along with the abrupt onset of other co-occurring symptoms (tics, behavioral and cognitive regression, etc.). PANS is thought to be a post-infectious immunopsychiatric disorder, although as with most post-infectious disorders, it is challenging to establish a causal relationship with proposed infectious triggers. Intravenous immunoglobulin (IVIG) can modulate inflammation and support the elimination of infection and has been used for treatment of many post-infectious inflammatory disorders and autoimmune conditions. The aim of the study is to explore the pro-inflammatory state in PANS before and after administration of IVIG. Children with moderate-to-severe PANS received six infusions of IVIG (Octagam 5%, Octapharma) every 3 weeks with post treatment follow-up. Blood samples and psychiatric measures were obtained at Visits 1 (pre-treatment), 7 and 8 (4 and 11 weeks after last infusion, respectively). Myeloid cell activation was assessed via flow cytometry. All ten patients included in the study were male, White, with mean age 12.4 years (range 6-16). Statistically significant improvements following IVIG treatment were demonstrated in all psychometric assessments and parent questionnaires including CY-BOCS (obsessive compulsive scale), YGTSS (tic scale) and a parent PANS rating scale (for all scales p<0.001). The fraction of pro-inflammatory monocytes and dendritic cells decreased from pre-IVIG treatment levels. The proportional reductions were not compensated by increases in total white blood cells; pro-inflammatory monocytes post-IVIG were decreased as a proportion of CD14+ myeloid cells and in absolute number. The results of this study suggest that active PANS is associated with a pro-inflammatory state. This pro-inflammatory profile and psychometric scores improved following IVIG treatment. Future work will aim to further elucidate the roles of innate and adaptive immune responses in PANS and the regulatory mechanism(s) of IVIG in PANS treatment.

Impact of Infliximab Biosimilar (Ixifi®) Trough Levels on Disease Activity and Inflammatory Markers in Iraqi Rheumatoid Arthritis Patients

Background: Rheumatoid arthritis is an autoimmune inflammatory condition that impacts the small and larger joints. Ixifi® is a biosimilar medication derived from infliximab that exclusively targets Tumor Necrosis Factor-α. Serum Ixifi® trough concentration is necessary to manage disease activity in rheumatoid arthritis. Objective: Assess the impact of the Ixifi® trough level on disease activity and inflammatory biomarkers. Methods: A cross-sectional observational study was undertaken at Baghdad Teaching Hospital, involving forty-two patients diagnosed with rheumatoid arthritis according to ACR/EULAR 2010 criteria. After 3 months after initiating therapy with Ixifi®, the serum concentrations of Ixifi®, as well as CDAI, ESR, and CRP biomarkers, were measured. Results: After 3 months of therapy with Ixifi®, the patients in the remission group had a higher concentration of Ixifi® compared to the mild, moderate, and severe disease activity groups. Ixifi® trough level in remission was 5.45 µg/ml, while in mild, moderate, and severe groups, it was 3.575 µg/ml, 2.2 µg/ml, and 0.66 µg/ml, respectively. The CDAI scores were in the severe group (26.0), moderate group (19.0), mild group (7.0), and remission group (2.0). Furthermore, the findings indicate an inverse correlation between the Ixifi® trough level and both ESR and CRP. Conclusions: A drop in Ixifi® levels leads to an increase in disease severity and inflammation, while high concentrations of Ixifi® decrease disease activity, ESR, and CRP.

Single-Cell Multi-Dimensional data analysis reveals the role of ARL4C in driving rheumatoid arthritis progression and Macrophage polarization dynamics

Rheumatoid arthritis (RA) is an enduring autoimmune inflammatory condition distinguished by continual joint inflammation, hyperplasia of the synovium, erosion of bone, and deterioration of cartilage.Fibroblast-like synoviocytes (FLSs) exhibiting “tumor-like” traits are central to this mechanism.ADP-ribosylation factor-like 4c (ARL4C) functions as a Ras-like small GTP-binding protein, significantly impacting tumor migration, invasion, and proliferation.However, it remains uncertain if ARL4C participates in the stimulation of RA FLSs exhibiting “tumor-like” features, thereby fostering the advancement of RA. In our investigation, we unveiled, for the inaugural instance, via the amalgamated scrutiny of single-cell RNA sequencing (scRNA-seq) and Bulk RNA sequencing (Bulk-seq) datasets, that activated fibroblast-like synoviocytes (FLSs) showcase high expression of ARL4C, and the ARL4C protein expression in FLSs derived from RA patients significantly surpasses that observed in individuals with osteoarthritis (OA) and traumatic injury (trauma).Silencing of the ARL4C gene markedly impeded the proliferation of RA FLSs by hindered the transition of cells from the G0/G1 phase to the S phase, and intensified cell apoptosis and diminished the migratory and invasive capabilities. Co-culture of ARL4C gene-silenced RA FLSs with monocytes/macrophages significantly inhibited the polarization of monocytes/macrophages toward M1 and the repolarization of M2 to M1.Furthermore, intra-articular injection of shARL4C significantly alleviated synovial inflammation and cartilage erosion in collagen-induced arthritis (CIA) rats.In conclusion, our discoveries propose that ARL4C assumes a central role in the synovial inflammation, cartilage degradation, and bone erosion associated with RA by triggering the PI3K/AKT and MAPK signaling pathways within RA FLSs.ARL4C holds promise as a prospective target for the development of pharmaceutical agents targeting FLSs, with the aim of addressing RA.

Immunometabolism of ferroptosis in the tumor microenvironment.

Ferroptosis is an iron-dependent form of cell death that results from excess lipid peroxidation in cellular membranes. Within the last decade, physiological and pathological roles for ferroptosis have been uncovered in autoimmune diseases, inflammatory conditions, infection, and cancer biology. Excitingly, cancer cell metabolism may be targeted to induce death by ferroptosis in cancers that are resistant to other forms of cell death. Ferroptosis sensitivity is regulated by oxidative stress, lipid metabolism, and iron metabolism, which are all influenced by the tumor microenvironment (TME). Whereas some cancer cell types have been shown to adapt to these stressors, it is not clear how immune cells regulate their sensitivities to ferroptosis. In this review, we discuss the mechanisms of ferroptosis sensitivity in different immune cell subsets, how ferroptosis influences which immune cells infiltrate the TME, and how these interactions can determine epithelial-to-mesenchymal transition (EMT) and metastasis. While much focus has been placed on inducing ferroptosis in cancer cells, these are important considerations for how ferroptosis-modulating strategies impact anti-tumor immunity. From this perspective, we also discuss some promising immunotherapies in the field of ferroptosis and the challenges associated with targeting ferroptosis in specific immune cell populations.

Reviving ancient therapeutics in modern medicine: an immunological and biological narrative review of wet cupping in the management of Hashimoto's thyroiditis.

The interwoven immunological, biological, and genetic complexity of thyroid diseases makes suitable targeted therapies particularly challenging to develop. Stemming from ancient practices, al-hijamah, or wet cupping, has achieved notable popularity in recent years, leading to unique applications in modern medicine. By grappling with the current literature that links the effects of wet cupping with the immune system in patients with Hashimoto's thyroiditis (HT), this narrative review aims to compose a comprehensive assessment of this adjunctive treatment based on evidence of its integration into practice. Between upregulating critical players of the innate immune system, such as immunostimulatory cytokines, white blood cells (WBCs) and natural killer (NK) cells, and downregulating essential thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) and inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), wet cupping practices provide promising complementary therapy for hypothyroidism. Wet cupping manipulates in vivo molecular mechanisms, as outlined in hemodynamic and microparticle clearance theories, to slow disease progression and even development in disease-free populations. Given the established utilization of wet cupping in the context of autoimmune diseases and inflammatory conditions, the emerging utility of wet cupping continues to gain credibility. This literature review illuminates the documented improvements in immune and biological function due to cupping therapeutic practices and sheds light on its appropriate application in the clinical setting for patients with HT. Furthermore, this review proposes a clear need for implementing future clinical trials, which may effectively bridge pathophysiological causes of hypothyroidism with underrated techniques for enhanced thyroid health.

Glucose-oxygen deprivation constrains HMGCR function and Rac1 prenylation and activates the NLRP3 inflammasome in human monocytes.

Hypoxia and low glucose abundance often occur simultaneously at sites of inflammation. In monocytes and macrophages, glucose-oxygen deprivation stimulates the assembly of the NLRP3 inflammasome to generate the proinflammatory cytokine IL-1β. We found that concomitant glucose deprivation and hypoxia activated the NLRP3 inflammasome by constraining the function of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate kinase pathway. HMGCR is involved in the synthesis of geranylgeranyl pyrophosphate (GGPP), which is required for the prenylation and lipid membrane integration of proteins. Under glucose-oxygen deprivation, GGPP synthesis was decreased, leading to reduced prenylation of the small GTPase Rac1, increased binding of nonprenylated Rac1 to the scaffolding protein IQGAP1, and enhanced activation of the NLRP3 inflammasome. In response to restricted oxygen and glucose supply, patient monocytes with a compromised mevalonate pathway due to mevalonate kinase deficiency or Muckle-Wells syndrome released more IL-1β than did control monocytes. Thus, reduced GGPP synthesis due to inhibition of HMGCR under glucose-oxygen deprivation results in proinflammatory innate responses, which are normally kept in check by the prenylation of Rac1. We suggest that this mechanism is also active in inflammatory autoimmune conditions.

Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic.

Autism spectrum disorder (ASD1) is a behaviorally defined syndrome encompassing a markedly heterogeneous patient population. Many ASD subjects fail to respond to the 1st line behavioral and pharmacological interventions, leaving parents to seek out other treatment options. Evidence supports that neuroinflammation plays a role in ASD pathogenesis. However, the underlying mechanisms likely vary for each ASD patient, influenced by genetic, epigenetic, and environmental factors. Although anti-inflammatory treatment measures, mainly based on metabolic changes and oxidative stress, have provided promising results in some ASD subjects, the use of such measures requires the careful selection of ASD subjects based on clinical and laboratory findings. Recent progress in neuroscience and molecular immunology has made it possible to allow re-purposing of currently available anti-inflammatory medications, used for autoimmune and other chronic inflammatory conditions, as treatment options for ASD subjects. On the other hand, emerging anti-inflammatory medications, including biologic and gate-keeper blockers, exert powerful anti-inflammatory effects on specific mediators or signaling pathways. It will require both a keen understanding of the mechanisms of action of such agents and the careful selection of ASD patients suitable for each treatment. This review will attempt to summarize the use of anti-inflammatory agents already used in targeting ASD patients, and then emerging anti-inflammatory measures applicable for ASD subjects based on scientific rationale and clinical trial data, if available. In our experience, some ASD patients were treated under diagnoses of autoimmune/autoinflammatory conditions and/or post-infectious neuroinflammation. However, there are little clinical trial data specifically for ASD subjects. Therefore, these emerging immunomodulating agents for potential use for ASD subjects will be discussed based on preclinical data, case reports, or data generated in patients with other medical conditions. This review will hopefully highlight the expanding scope of immunomodulating agents for treating neuroinflammation in ASD subjects.

Systemic inflammation response index is associated with increased all-cause and cardiovascular mortality in US adults with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) stands as a persistent systemic inflammatory autoimmune condition. Despite this understanding, the precise impact of the systemic inflammation response index (SIRI) on the prognosis of RA patients remains elusive. This study aims to elucidate the correlation between the inflammatory biomarker SIRI and both all-cause mortality and cardiovascular mortality among RA patients. MethodsUtilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020, a retrospective analysis was conducted. Survival data were depicted through Kaplan-Meier survival curves, while the relationship between SIRI and all-cause or cardiovascular mortality in RA patients was scrutinized via multivariable Cox proportional hazards regression analysis and restricted cubic spline plots. Furthermore, subgroup analysis and mediation analysis were also performed. ResultsThis study encompassed 2656 RA patients with a comprehensive 20-year follow-up, during which 935 all-cause deaths and 273 deaths attributed to cardiovascular disease were recorded. We observed a nonlinear positive correlation between SIRI with both all-cause and cardiovascular mortality in RA patients. Notably, at a SIRI level of 1.12, the hazard ratio reached 1, indicating a shift from low to high mortality risk. Furthermore, mediation analysis revealed that 12.6% of the association between RA and mortality risk was mediated through SIRI. Subgroup analysis indicated a more pronounced association between SIRI and mortality in female patients or those with a high BMI. ConclusionThis study underscores a non-linear positive correlation between the biomarker SIRI and both all-cause mortality and cardiovascular mortality in RA patients.

Inflammatory Markers in Thyroid Eye Disease: A Meta-Analysis

ABSTRACT Thyroid Eye Disease (TED) is an inflammatory autoimmune condition affecting the eyes, often associated with Graves’ disease. Inflammation is important in TED, involving immune cells and orbital tissues. While inflammatory markers have been studied in other diseases, their role in TED is unclear. We included 734 participants from 5 eligible studies investigated associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) and TED. Initial analysis found no significant differences in these markers between TED and control groups. However, sensitivity analysis excluding an outlier study revealed significant differences in NLR, PLR, and MLR between groups, suggesting the potential association between these inflammatory markers and TED. More research is needed, but these findings indicate complex TED pathogenesis and that inflammation may offer insights for TED diagnosis and management.

JAK2/STAT3 Pathway Inhibition by AG490 Ameliorates Experimental Autoimmune Encephalomyelitis via Regulation of Th17 Cells and Autophagy

Multiple sclerosis (MS) is an autoimmune inflammatory condition affecting the central nervous system, and experimental autoimmune encephalomyelitis (EAE) animal models have been extensively used to study it. T-helper 17 cells, which produce interleukin-17(IL-17), play crucial roles in MS pathogenesis, and the JAK2/STAT3 pathway has an essential function in their differentiation from naive CD4 + T cells. This study investigated the effects of the JAK2/STAT3 pathway inhibitor AG490 on EAE in vivo and in vitro, as well as the underlying mechanisms. AG490 ameliorated EAE severity and attenuated its typical symptoms by downregulating proteins associated with the JAK2/STAT3 pathway. Furthermore, it decreased T-helper 17 cell differentiation from naive CD4 + T cells by inactivating STAT3. In addition, it conferred protective effects against EAE by restoring autophagy. These findings indicate the potential of AG490 as a candidate anti-MS therapeutic.

Osteopontin as a Biomarker in Interstitial Lung Diseases.

Osteopontin (OPN) is a glycoprotein involved in Th1 and Th17 differentiation, and inflammation and tissue remodeling. OPN is a biomarker of disease activity in patients with autoimmune inflammatory conditions. This study aimed to assess the diagnostic and prognostic value of OPN in interstitial lung diseases (ILDs). Between May 2016 and October 2019, 344 patients with ILD were recruited at the Hospital Universitario Marqués de Valdecilla (Spain) and were prospectively followed-up. This study involved the determination of OPN serum levels by ELISA and OPN RNA expression quantified using qPCR. Six genetic polymorphisms in OPN (rs28357094, rs2853749, rs2853750, rs11728697, rs7695531, and rs1126616) were genotyped using TaqMan assays. OPN serum levels were also assessed in 140 healthy controls. OPN serum levels (median [interquartile range]) were significantly higher in ILD patients than in controls (1.05 [0.75-1.51] ng/mL versus 0.81 [0.65-0.98] ng/mL in healthy controls; p < 0.01). OPN serum levels were inversely correlated with the forced vital capacity. OPN serum levels were also higher in ILD patients who died or underwent lung transplantation when compared with the remaining ILD patients (1.15 [0.80-1.72] ng/mL versus 0.99 [0.66-1.32] ng/mL; p = 0.05). Survival worsened in ILD patients with OPN > 1.03 ng/mL at 1, 3, and 5 years. No statistically significant differences in the genetic frequencies of OPN polymorphisms or the RNA expression were found among the different ILD groups. Elevated levels of OPN in the serum may be a useful indicator in identifying patients with ILD who are more likely to experience poor outcomes.

BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population.

Pakistan is endemic to a diverse set of parasitic, mycobacterial and viral diseases. The recognition of BCG Trained Immunity (TI) led us to postulate that the continued presence of BCG-TI may play a protective role, previously reported for both infectious and noninfectious conditions. Most of the previous studies have addressed the issue of BCG-TI in the paediatric populations. This study addressed the key issue of maintenance of BCG-TI in a wider age range (adolescent and adults) to identify the strength and quality of the immune responses. To assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections. In this cross-sectional study, healthy young adults and adolescents (n = 20) were recruited from 16-40 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition. BCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network [macrophages [M1 (TNFα, IFNγ), M2 (IL10)], NK (IL2), Gamma delta (γδ) T (IL17, IL4)] and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay. Significant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNFα (9148 pg/ml) followed by IL10 (488 pg/ml) and IFNγ (355 pg/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNFα, 40 fold fo r IL10, and 27 fold for IFNγ. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG. The presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro- and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.

Single-cell RNA sequencing reveals an immunomodulatory population of double negative T-cells in the diabetic NOD mouse

Abstract NOD mice are a widely used model of type 1 diabetes, an inflammatory autoimmune condition characterized by autoreactive T-cells that target insulin producing beta cells of the pancreatic islets. While T cell biology in the context of this disease is important it is unclear why autoreactive T-cells develop in this model or what they do within the islets themselves. We have designed a single cell sequencing experiment where enriched T-cells taken from diabetic and non-diabetic NOD mice are sequenced for mRNA expression and TCR sequence concurrently. The resulting sequencing data shows abnormal representation of Double Negative (DN) T-cells in all tissues and conditions (~30%). We have observed that like CD8+ and CD4+ T-cells, this population displays normal maturation phenotypes, but experience reduced exhaustion of effector subsets after infiltration of the pancreatic islets. Looking at clonal subpopulations of T-cells we have discovered a subset of CD8+ T-cells that have high expression of GzmA even after loss of the survival signal marker, IL7r. Through investigation of these aberrant T-cell populations, we have found that the diabetic NOD mouse pancreatic is highly immunosuppresive and expression of T-cell co-receptors may have a significant impact on diabetic onset.

Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory autoimmune condition characterized by synovitis, pannus formation (with adjacent bone erosion), and joint destruction. In the perpetuation of RA, fibroblast-like synoviocytes (FLSs), macrophages, B cells, and CD4+ T-cells-specifically Th1 and Th17 cells-play crucial roles. Additionally, dendritic cells, neutrophils, mast cells, and monocytes contribute to the disease progression. Monocytes, circulating cells primarily derived from the bone marrow, participate in RA pathogenesis. Notably, CCR2 interacts with CCL2, and CX3CR1 (expressed by monocytes) cooperates with CX3CL1 (produced by FLSs), facilitating the migration involved in RA. Canonical "classical" monocytes predominantly acquire the phenotype of an "intermediate" subset, which differentially expresses proinflammatory cytokines (IL-1β, IL-6, and TNF) and surface markers (CD14, CD16, HLA-DR, TLRs, and β1- and β2-integrins). However, classical monocytes have greater potential to differentiate into osteoclasts, which contribute to bone resorption in the inflammatory milieu; in RA, Th17 cells stimulate FLSs to produce RANKL, triggering osteoclastogenesis. This review aims to explore the monocyte heterogeneity, plasticity, antigenic expression, and their differentiation into macrophages and osteoclasts. Additionally, we investigate the monocyte migration into the synovium and the role of their cytokines in RA.

Cardiovascular Morbidity in Systemic Lupus Erythematosus: A Single-Center Retrospective Study.

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory condition affecting multiple systems. Cardiovascular morbidity is a significant concern, with around 25% of SLE patients experiencing cardiac complications. This study aims to determine the prevalence of cardiovascular morbidity in SLE patients in King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia. This retrospective record-based research was conducted at KFMC from January 2015 to October 2023. A review of the medical files of all SLE patients was accomplished. The vast majority of the patients (90.9%) were females. The mean age for the patients was 36.5 years. The most common comorbidities were lupus nephritis (34.6%), hypothyroidism (18.4%), and anti-phospholipid syndrome (9.2%). The most commonly used medications were hydroxychloroquine (81.8%), corticosteroids (prednisolone) (43.0%), and mycophenolate mofetil (27.9%). Around 45.2% (n= 176) of the patients with SLE developed cardiovascular complications. The most commonly reported cardiovascular diseases that developed after diagnosing patients with SLE were hypertension (22.4%), valvular heart diseases (13.2%), and dyslipidemia (9.2%). The study also found that anti-dsDNA antibodies can reduce the likelihood of developing hypertension by 40%. This research contributes to the medical literature on SLE and sets the stage for future research on personalized healthcare strategies for managing SLE and its complications. This study highlights that a considerable proportion of SLE patients(~50%) develop cardiovascular complications, with hypertension, valvular heart diseases, and dyslipidemia being the most common. We also discovered that anti-double-stranded deoxyribonucleic acid antibodies (Anti-dsDNA) reduce the likelihood of developing hypertension.

Unresolved Malady of Pyoderma Gangrenosum: A Study of its Profile and Outcome in a Tertiary Care Center

Introduction: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of uncertain etiology characterized by rapidly progressive, painful skin ulcers, and is often difficult to diagnose. The common underlying disease associations include rheumatoid arthritis (RA), inflammatory bowel disease (IBD), autoimmune inflammatory conditions, and malignancies, both hematological and solid organ tumors. Aims and Objectives of the Study: Assess the demographics, clinical presentation and associated systemic diseases, and response to treatment of patients with pyoderma gangrenosum. Materials and Methods: In this retrospective study, all cases diagnosed as PG were evaluated along with disease associations and outcomes over a 5-year period. Results: A total of 42 patients’ charts were studied of which, ulcerative PG was seen in 86.4%, pustular in 16.8%, bullous in 14.4%, and vegetative in 2.4% patients, respectively. Thirty-six percentage of them had RA, 12% had non-RA connective tissue disease, 9.6% had IBD, 9.6% had chronic liver disease, and 4.8% had malignancy. Positive pathergy was seen in 57% of our study patients. Multiple morphological types with recurrences were more common in patients with positive pathergy. Mortality was seen in 9.6% of patients. Statistics: Descriptive statistics were reported as mean with standard deviation, number, and percentages. Association between the clinical characteristics of the variables was done using Chi-square test. Conclusion: PG with multiple morphological types with multifocality is frequently associated with exacerbation of the underlying disease. RA was the most common association found. Recurrent disease was more common in older patients (&gt;40 years).

A Study of Assessment of Preclinical Atherosclerosis by Carotid Intima-media Thickness in Newly Diagnosed Patients with Rheumatoid Arthritis Younger than 50 Years of Age and Their Correlation with Disease Activity: A Comparative, Cross-sectional Study

Abstract Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition that has been linked to an increased risk of atherosclerosis and enhanced cardiovascular disease (CVD) risk. Most literature encompasses older age groups. Objectives: This study aimed to determine the carotid intima-media thickness (CIMT) in patients with newly diagnosed RA who are younger than 50 years of age and do not display the symptoms or traditional risk factors of CVD and compare it to the controls with same age and gender without RA. Furthermore, the correlation between CIMT and the disease activity Score -28 (Erythrocyte sedimentation rate) were examined. Subjects and Methods: The study enrolled 48 patients with RA and 51 healthy controls who met the study’s inclusion and exclusion criteria. All patients underwent CIMT by the ultrasound. Results: There was a significant increase in common carotid artery CIMT on both the right and left sides (P &lt; 0.001) in RA patients as compared to controls. The correlations between CIMT (right and left) and DAS 28 ESR were only poor and negative. Conclusion: Younger patients with RA showed higher CIMT than age- and sex-matched controls, indicating an increased risk of future cardiovascular events even in the young.

KcsA-Kv1.x chimeras with complete ligand-binding sites provide improved predictivity for screening selective Kv1.x blockers

Despite significant advances in the development of therapeutic interventions targeting autoimmune diseases and chronic inflammatory conditions, lack of effective treatment still poses a high unmet need. Modulating chronically activated T cells through the blockade of the Kv1.3 potassium channel is a promising therapeutic approach, however, developing selective Kv1.3 inhibitors is still an arduous task. Phage display-based high throughput peptide library screening is a rapid and robust approach to develop promising drug candidates; however, it requires solid-phase immobilization of target proteins with their binding site preserved. Historically, the KcsA bacterial channel chimera harboring only the turret region of the human Kv1.3 channel was used for screening campaigns. Nevertheless, literature data suggest that binding to this type of chimera does not correlate well with blocking potency on the native Kv1.3 channels. Therefore, we designed and successfully produced advanced KcsA-Kv1.3, -Kv1.1 and -Kv1.2 chimeric proteins in which both the turret and part of the filter regions of the human Kv1.x channels were transferred. These T+F (turret-filter) chimeras showed superior peptide ligand binding predictivity compared to their T-only versions in novel phage ELISA assays. Phage ELISA binding and competition results supported with electrophysiological data confirmed that the filter region of KcsA-Kv1.x is essential for establishing adequate relative affinity order among selected peptide toxins (Vm24 toxin, Hongotoxin-1, Kaliotoxin-1, Maurotoxin, Stichodactyla toxin) and consequently obtaining more reliable selectivity data. These new findings provide a better screening tool for future drug development efforts and offer insight into the target-ligand interactions of these therapeutically relevant ion channels.