Autoimmune Disease

Cutaneous lesions are among the earliest and most frequent features of SLE, with over 70% of patients developing mucocutaneous involvement during their disease course. The presence and severity of cutaneous manifestations have been associated with specific autoantibodies, such as anti-Ro/SSA and anti-dsDNA, which may reflect underlying genetic susceptibility. Recent studies have also implicated gene polymorphisms in IRF5, STAT4, TREX1, and TNFA in the pathogenesis of cutaneous SLE phenotypes. Defective TREX1 exonuclease activity, leading to intracellular accumulation of DNA, may trigger type I interferon activation-a key mechanism in lupus pathophysiology. Despite the extensive global literature, data from Egyptian patients remain limited, especially regarding the relationship between TREX1 gene variants and cutaneous lupus phenotypes. Understanding how autoantibody profiles and gene polymorphisms relate to clinical features and disease activity could enhance early diagnosis, predict flares, and improve personalized therapy.

Background: Rheumatoid arthritis (RA) RA is one of the most common autoimmune diseases, characterized by chronic inflammation of the sinovia, mainly of the small joints of the hand, wrists and feet. Chronic inflammation can lead to the destruction of cartilage and joint bone, causing joint deformity, functional disability, depression and significant economic costs for the affected individual. α-tocopherol acetate: The α-tocopherol acetate is the most widely used analogue in food supplements because of its esterification gives it stability. The main function is antioxidant preventing lipid oxidation of cell membranes for this reason α-tocopherol is considered a possible protector against diseases related to oxidative processes such as chronic diseasedegenerative diseases such as diabetes mellitus, cancer, cardiovascular disease, rheumatic disease, neurological disease and ageing. Vitamin E in RA: The role of vitamin E as a therapy in combination with RA treatment has been studied in several studies. Studies in mouse models of laminarin-induced arthritis have shown that supplementation with α-tocopherol decreases the expression of pro-inflammatory cytokines such as IL-6, TNF-α and MMPs. However, the mechanisms involved are unknown. There are few studies in RA patients where the effect of supplementation with α-tocopherol has been analyzed. In clinical trials, it has been observed that from 3 weeks with supplementation of α-tocopherol decreases the scales of clinical activity in addition to morning stiffness and joint pain even biochemical parameters such as acute phase reactants such as pCr and ESR. However, the effect on pro-inflammatory cytokines, autoantibodies and antioxidant effect has not been analyzed. Research question: Is supplementation with Vitamin E (α-tocopherol) for one month associated with decreased clinical activity and inflammation in patients with RA? Specific objectives 1. Analyze the clinical characteristics and diet quality of RA patients 2. Determine serum autoantibody levels in RA patients 3. Quantify serum vitamin E levels before and after supplementation in both study groups (Vitamin E and placebo) 4. Compare clinical activity before and after supplementation in both study groups 5. Quantify serum concentration of pro-inflammatory cytokines IL1β, IL6 and TNF-α before and after supplementation in both study groups 6. Determine antioxidant capacity before and after supplementation in both study groups 7. Associate vitamin E levels with clinical and inflammatory parameters of patients with RA Hypothesis : There is an association between supplementation with vitamin E (α-tocopherol) and decreased clinical activity and inflammation in patients with RA from western Mexico Methodological design: a) Study type - Clinical, randomized, controlled and double-blind trial. Research sites: * Institute of Biomedical Sciences (IICB) of the University Center for Health Sciences (CUCS) * Laboratory for Clinical Analysis and Translational Research (LACIT), at the University Center for Exact Sciences and Engineering (CUCEI) * Rheumatology Service of the Civil Hospital "Fray Antonio Alcalde" in Guadalajara, Jalisco. Time to develop: January 2025 to January 2027. Sample size: The statistical formula of two averages was used for the calculation of the sample size. The calculations were made with data from the corresponding 2001 clinical trial of Mona Helmy and colleagues, resulting in a sample size of 19 patients plus an increase of 20% to cover possible losses. Having 23 patients for control and intervention group. Both groups with RA of the Rheumatology Service of the Civil Hospital "Fray Antonio Alcalde" in Guadalajara, Jalisco. Variables Independent variables * Vitamin E Dependent variables * Inflammatory cytokines (IL-1β, IL-6 and TNF-α). Antioxidant capacity:( DPPH, ABTS, FRAP and ORAC). Clinical evolution: DAS-28. Acute phase reactants: pCr and ESR. Auto-antibodies: Anti-ccp and rheumatoid factor. Biosafety considerations: This study will apply the guidelines set out in the Mexican Official Standards, NOM-052-SEMARNAT-2005, NOM-054-SEMARNAT-1993 and NOM-087-ECOL-SSA1-2002 that refer to classification, Handling, storage and disposal of hazardous waste, chemical reagents and biological-infectious wastes, in order to ensure the protection of people in contact with them and the environment. Ethical considerations: The project will be carried out in accordance with the ethical standards and principles for medical research on human beings, as set out in the Declaration of Helsinki, which were last reviewed at the 64th General Assembly, Fortaleza, Brazil, October 2013, which refers to ethical principles for medical research in humans.

The investigators aim to validate a novel, cost-effective method for real-world assessment using patient-acquired "selfie" videos. The investigator's preliminary data demonstrate feasibility, validity and utility of this technology, which overcomes limitations of existing digital biomarkers and offers a truly patient-centered, low-burden approach to monitoring and treating diverse people with MS (PwMS). The investigators want to understand the barriers and facilitators to adoption of this approach, as well as the real-world validity and impact of the data generated. This will allow investigators to share the most accessible, generalizable and useful protocols and metrics with the MS community. This approach to digital tool development prioritizes patients and clinicians. Indeed, the investigators leverage a tool used every day by the general population ("selfie" videos) that recapitulates clinicians' primary examination tool: observing how patients talk and walk. This approach uses the patient's own device (device agnostic: including smartphones sold after 2010, as well as tablets, laptops or desktops with camera capture), without requiring proprietary software or technology, to collect "selfie" videos - which are ubiquitous in modern life - and provides a link to a secure web portal for simple uploading. The task minimizes burden: it is brief (5 \<1min videos), can be done in individuals' own homes, requires no direct or indirect costs, and therefore is accessible to many diverse patients. Digital biomarkers must demonstrate VALIDITY: sensitivity to subtle change over time, but also relevance to an individual's daily life and function (i.e. veridicality and verisimilitude). Patient selfie videos capture activities relevant in daily life (buttoning a shirt, walking down a hallway, talking about one's morning), across all levels of disability, using assessments that are holistic and that have veridicality and verisimilitude. Furthermore, the metrics show greater sensitivity to change than standard assessments. Overall objective: Validate video "selfies" as a patient-centered, valid, comprehensive longitudinal data collection method in MS. This approach will be deemed successful if the investigators achieve key metrics informed by implementation science and digital monitoring biomarker validation as necessary for dissemination, which surpass the feasibility, usability or validity of most digital tools currently available for monitoring in MS.

Sexual health is an integral component of overall well-being and quality of life, including for adults living with chronic diseases such as diabetes. Despite its importance, sexual health is often overlooked in clinical practice. Health care professionals rarely initiate conversations about sexual functioning due to limited training, lack of tools, or concern about patient discomfort. At the same time, many patients with diabetes report fear of hypoglycemia during or after sexual activity, and partners frequently share similar concerns. These fears may lead to reduced sexual activity and diminished quality of life. Hypoglycemia remains one of the most common and clinically significant complications of insulin therapy. Glucose levels below 70 mg/dL require prompt intake of carbohydrates or adjustment of glucose-lowering treatment to prevent further decline. Physical exertion- including sexual activity-may lead to early or delayed hypoglycemia, occurring even several hours after the activity. On the other hand, emotional excitement during sexual activity may trigger counter-regulatory hormones such as adrenaline or cortisol, potentially causing hyperglycemia. Despite these observations, no systematic study has evaluated the relationship between sexual activity and glucose fluctuations in adults with diabetes. Historically, such research was hindered by the intimate nature of the subject and the absence of remote monitoring tools. The introduction of continuous glucose monitoring (CGM) systems, together with cloud-based platforms such as LibreView and Dexcom Clarity, enables the remote and secure assessment of glucose trends without requiring direct discussion of intimate details. This study leverages these technologies to evaluate whether sexual activity increases the risk of hypoglycemia in adults with type 1 or type 2 diabetes treated with insulin. Each participant will be observed for 3 months. Participants will mark the beginning of sexual activity within their CGM application using a neutral icon (e.g., a heart symbol). Glucose trends during and for up to 6 hours following the activity will be analyzed and compared to glucose profiles from days without sexual activity. Health care providers will also complete a brief online form with basic clinical information about each participant, including age, diabetes type, disease duration, treatment regimen, and CGM system used. The study aims to enroll 100 adults. This pragmatic sample size reflects the exploratory nature of the project and the absence of prior research in this area. Based on general population estimates, participants are expected to report an average of approximately 10 episodes of sexual activity over the 3-month observation period. The primary endpoint is the proportion of sexual activity episodes associated with hypoglycemia, defined as glucose levels below 70 mg/dL occurring during or after the activity. All data will be anonymized. Each patient will receive a unique study code that does not contain personal identifiers. Only the principal investigator and scientific supervisor will have access to the code key. Glucose data and sexual activity markers will be exported from CGM applications in encrypted form and analyzed exclusively in de-identified datasets. After completion of the study and statistical analysis, all data will be securely deleted according to institutional procedures. The results of this study may provide the first empirical evidence on the relationship between sexual activity and hypoglycemia risk in individuals using insulin therapy. If a relationship is confirmed, the findings may guide future recommendations to improve safety around sexual activity. If no association is found, the results may help reduce unnecessary anxiety among patients and improve open communication in clinical practice.

Subject Enrollment This study will consent and enroll 20 subjects total. • For Arm 1, 10 subjects with Idiopathic Pulmonary Arterial Hypertension (IPAH) will be consented and enrolled. For Arm 2, 10 subjects with Connective Tissue Disease Associated Pulmonary Arterial Hypertension (PAH-CTD) will be consented and enrolled. Study Design This study will be observational. Subjects in both arms of the trial will undergo a 129Xe MRI/MRS at timepoints of baseline, 3 months, 6 months, and 12 months. In addition to the this, data from standard of care assessments, such as labs, echocardiography, and six-minute walk distance (6MWD), will also collected at these timepoints. Primary Study Endpoints The primary endpoint for this trial will be the change in defect + low percentage of RBC signal on hyperpolarized 129Xe MRI from baseline to 12 months Secondary Study Endpoints There will be several secondary endpoints for this trial: * Change in regional and global RBC Oscillation Amplitudes on hyperpolarized 129Xe MR spectroscopy from baseline to 12 months * Change in 6MWD from baseline to 12 months * Change in NTproBNP from baseline to 12 months * Change in WHO FC from baseline to 12 months Primary Safety Endpoints There will be several primary safety endpoints for this trial: * Frequency of Adverse Events (AE) and/or Serious Adverse Events (SAE) * Withdrawals due to adverse event or death * Incidence of Adverse Events of Significant Interest (AESI): * Electrocardiogram and any findings * Physical examination and vital signs

Multiple sclerosis is a common inflammatory disease of the central nervous system and the leading cause of non-traumatic physical disability in young adults. Spinal cord involvement is common, affecting approximately 90% of patients, and can be revealed by sensory loss, neuropathic pain, spasticity, motor weakness, and bladder and bowel dysfunction. Spinal cord imaging plays an important role in the diagnosis of the disease, but also in the prognosis, particularly with regard to the location and severity of the damage. Due to the location, small size and mobility of the spinal cord, its imaging raises technical problems and fewer studies have focused on spinal cord involvement in MS than on brain involvement. Currently, the 2D sagittal T2 FSE sequence is the imaging of choice for spinal cord analysis. Numerous sequences have been developed recently, some of which show an increase in sensitivity at the cervical level, such as short tau inversion recovery (STIR) and phase sensitive inversion recovery (PSIR). The lesion load assessed on these conventional sequences lacks correlation with clinical status, probably due to a multifactorial mechanism of disability in MS, but also probably due to the limitations of the resolution of current sequences. WHINUME study will investigate at the spinal cord level the interest of an optimised MP-RAGE sequence cancelling the spinal cord white matter signal. The hypothesis is that this sequence could have a good sensitivity, specificity and reproducibility between readers for the detection of spinal cord lesions compared to other sequences at the cervical level but also at the thoracic level. Therefore, it could replace the conventional sequences currently available. This study will prospectively include 60 patients with multiple sclerosis confirmed by the McDonald 2017 criteria. All patients will sign a consent form. The 3D OPTIMIZED MPRAGE WMN will be compared to conventional sequences.

This study is a prospective, case-control study evaluating whether the PET radiotracer 68Ga-FAPI-46 can detect fibrostenosing Crohn's disease in the small bowel. The goal is to determine whether areas of early or developing fibrosis ("pre-stricture" changes) demonstrate uptake of the tracer, which binds to fibroblast activation protein (FAP). Participants with small bowel Crohn's disease will be assigned to either a case or control group based on CT or MR enterography findings at enrollment. Cases will include participants who have a small bowel stricture or probable stricture, with or without penetrating complications. Controls will include participants with small bowel Crohn's disease without strictures. Controls may have active inflammatory disease, luminal narrowing, or no active inflammation (including postoperative or chronic changes), as long as no stricture is present. Because most radiologic strictures represent more advanced fibrostenosis, the study aims to enroll a larger proportion of controls to better characterize early fibrotic changes. Approximately one-third to one-half of participants will be cases, and the remainder controls. This design will allow comparison of FAPI uptake patterns in patients with and without strictures to understand how FAP expression relates to the development of small bowel fibrosis.

\[68Ga\] Ga-FAPI is an innovative radiotracer in positron emission tomography (PET) coupled to scanner (CT: computed tomography). It targets the membrane glycoprotein FAP (Fibroblast Activation Protein), a specific surface marker of activated fibroblasts, these constituting one of the main populations of the tumor microenvironment. This radiotracer is the subject of a major development program in the field of oncology and hematologic malignancies. In many cancers, preliminary data suggest, in terms of diagnostic performance, the superiority of \[68Ga\] Ga-FAPI over the reference evaluation modality carried out with \[18F\] F-FDG. These results make it possible to consider, in the medium term, the integration of this imaging modality into routine care, for the initial evaluation and monitoring of certain tumor pathologies. If oncology and hematology constitute the most obvious areas of application of \[68Ga\] Ga-FAPI, other areas of potential use were quickly mentioned, due to the involvement of activated fibroblasts in the processes. remodeling of the extracellular matrix and tissue repair in general, beyond tumor pathologies. Non-exhaustively, the potential interest of the radiotracer is thus suggested in the characterization of benign tumor pathologies, in the evaluation of ischemic tissues, in chronic inflammatory diseases and in fibrosing diseases. Numerous preliminary data show that it is relevant to develop knowledge concerning the contribution of \[68Ga\] Ga-FAPI to the evaluation of numerous benign pathologies. It is in this general context that this single-center pilot study project falls, the general objective of which is to determine the preliminary interest of this imaging modality in different chronic inflammatory and/or fibrosing diseases. The pathologies included in this project were selected by taking into account the concomitant presence of unmet medical needs in terms of disease assessment and recognized local clinical research expertise in the area concerned. On these bases, 15 distinct clinical situations were selected, intended to enable the production of pilot data. This approach will be able to determine the interest in continuing clinical development in each area and will help to specify the modalities. The 13 clinical situations selected for this pilot study are: * Rheumatoid arthritis * Spondyloarthritis * Inflammatory enterocolopathies * Liver fibrosis * Fibrosing interstitial lung disease * Systemic sarcoidosis * Polymyalgia rheumatica and giant cell arteritis * Primary Sjögren's syndrome * Systemic scleroderma * Systemic lupus * Inflammatory myopathies * Primary or secondary myelofibrosis * Other orphan systemic diseases * Endometriosis * Chronic thrombo embolic disease

The revolution in rheumatoid arthritis (RA) therapeutics has been transformative for many patient outcomes. Yet most patients continue to experience life disabling pain. Strikingly, even those who achieve full disease remission with state-of-the-art anti-tumour necrosis factor (TNF) treatments report substantially higher levels of pain when compared to the general population. Such disconnect presents one of the greatest contemporary challenges to the care of patients with RA. Considering the ongoing excess burden of pain in this patient population, trials of Janus kinase inhibitors (JAKinibs) present welcome data. JAKinibs deliver superior pain improvements in comparison to those receiving anti-TNF therapy. Of note, the majority of this effect has not been fully explained by markers of peripheral inflammation and remains to be understood. Moreover, JAKinibs appear to offer rapid analgesic benefit. Traditional DMARDS and modern biologics commonly take several weeks to bring relief whereas JAKinibs, such as filgotinib, begin to improve pain as early as 2 weeks, even before the observed attenuation of peripheral clinical inflammation. In light of these clinical observations, the investigators believe that RA is a mixed pain state i.e., pain pathways exist in addition to established peripheral inflammatory nociceptive mechanisms. In particular, the central nervous system (CNS) may have an important role in determining RA pain. Recently our group were the first to delineate distinct neurobiological pain signatures in the brains of RA patients by employing functional connectivity magnetic resonance imaging (fcMRI) - a recent adaptation of functional MRI data that examines the synchrony of neural activity which modulates the efficiency and extent of neuronal transmission between brain regions. Specifically, the investigators identified and replicated two distinct pain signatures: 1. enhanced functional connectivity between the Default Mode Network (DMN) and insula, which was unrelated to levels of peripheral inflammation but, intriguingly, is an established neurobiological marker of fibromyalgia (the prototypical CNS pain sensitization disorder, and 2. enhanced functional connectivity between the Dorsal Attention Network (DAN) and the left inferior parietal lobule (LIPL) which was related to levels of peripheral inflammation. Pre-clinical experiments have not only implicated the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway with peripheral immune system functioning but also the brain. In the CNS, this pathway promotes gene expression associated with inflammation which in turn generates pro-nociceptive cytokines. However, there is now also emerging evidence to support the pathway's direct role in synaptic transmission and neurotransmitter receptor modulation. Specifically, the JAK-STAT pathway appears important in N-methyl-d-aspartate (NMDA) related synaptic plasticity - a ubiquitous glutamate receptor of the human brain. Their induction is selectively blocked by JAK inhibitors. Increases in glutamate and subsequent binding to NMDA receptors cause chaotic and incoherent neuronal functional activity. Human studies of fibromyalgia have consistently evidenced both elevated glutamate levels within the insula and dysfunctional neural connectivity. Moreover, fibromyalgia pharmacotherapy (pregablin), considered to reduce neural glutamate, rectifies both insular glutamate and brain functional connectivity (DMN-insula). JAK inhibition (JAKi) may facilitate the reduction of glutamate-NMDA binding and ultimately pain alleviation by normalising the functional activity of these same neural connections.

Litifilimab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting blood dendritic cell antigen 2. It is an inhibitory receptor expressed on the surface of human plasmacytoid dendritic cell (pDCs) and is being investigated for the potential treatment of systemic lupus erythematosus and cutaneous lupus erythematosus. The primary objectives of the study are to evaluate the efficacy of litifilimab compared with placebo in reducing skin disease activity measured by the CLA-IGA-R score \[Parts A\] and the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score \[Part B\] in participants with active SCLE and/or CCLE with or without systemic manifestations and refractory and/or intolerant to antimalarials. The secondary objectives of the study are to evaluate the efficacy of litifilimab in reducing SCLE and/or CCLE disease activity by CLA-IGA-R, CLASI-A; to evaluate additional efficacy parameters of litifilimab in reducing SCLE and/or CCLE disease activity; safety; tolerability; and immunogenicity of litifilimab \[Parts A and B\].