Jessica Matts, Ph.D.’s Post

#ChimericAntigenReceptor T-cell (#CART) #therapy, initially developed for #cancerTreatment, is showing promise in inducing remission in #autoimmune diseases like #lupus. By genetically modifying a patient's T-cells to target and eliminate malfunctioning B-cells, this approach offers potential for long-term remission without continuous medication. 10 Key Takeaways: 1. Innovative Application: CAR-T therapy is being repurposed to treat autoimmune diseases by eradicating autoreactive B-cells responsible for conditions like lupus. 2. Clinical Success: Early studies report that patients with severe lupus have achieved complete remission following CAR-T therapy, with some remaining symptom-free for extended periods. 3. Mechanism of Action: The therapy involves engineering T-cells to express receptors that specifically target and destroy B-cells contributing to autoimmune activity. 4. Potential for Cure: While traditionally considered incurable, autoimmune diseases like lupus may become manageable or even curable through this innovative treatment. 5. Broader Implications: Success in lupus treatment suggests CAR-T therapy could be effective against other autoimmune diseases, including multiple sclerosis and myasthenia gravis. 6. Research Expansion: Ongoing clinical trials are exploring the efficacy of CAR-T therapy across various autoimmune conditions, aiming to establish broader therapeutic applications. 7. Patient Impact: Individuals undergoing CAR-T therapy have experienced significant improvements, reducing or eliminating the need for lifelong immunosuppressive medications. 8. Safety Profile: While promising, CAR-T therapy carries risks such as cytokine release syndrome, necessitating careful patient monitoring and management. 9. Cost and Accessibility: The complexity and expense of CAR-T therapy present challenges, prompting efforts to develop more accessible and affordable treatment options. 10. Future Directions: Advancements aim to refine CAR-T therapy, enhancing its safety, efficacy, and applicability to a wider range of autoimmune diseases. #CARTCellTherapy #AutoimmuneDisease #LupusTreatment #MedicalBreakthrough #Immunotherapy #ChronicIllness #PatientCare #InnovativeMedicine #HealthcareAdvancement #RemissionHope Source: https://lnkd.in/en2eSU_8

https://lnkd.in/drzK-i5F FOUR TO SIX YEARS OF RHEUMATOLOGIC COMPLAINS!!! A MUST READ PAPER!!! Chikungunya comes from the Makonde language and means “bent over in pain”!!! This is the first study to follow patients four to six years after human chikungunya infection to understand the relationship between T cell immunology and arthritis disease activity over time. The study sample averaged nearly 4- and 6-years post-infection at the 2 study assessment times. The primary finding from this study was that rheumatologic symptoms persisted after CHIKV infection with mild to moderate intensity but that arthritis disease activity, Teff and Treg populations and activation markers waned over time. This cohort study describes the T-cell immunology of a special group of patients with persistent arthritis an average of four years after infection with CHIKV. Authors found that the arthritis was still mild to moderate in intensity four to six years after initial infection with persistent effects on disability, pain, stiffness, fatigue, sleep disturbances, depression, physical function, and mobility. 

a list of fungus toxins that can cause liver damage and pain: 1. Aflatoxins (Aspergillus): Can cause liver damage, scarring, and cancer 2. Ochratoxin A (Aspergillus, Penicillium): Can cause liver damage, kidney damage, and cancer 3. Trichothecenes (Fusarium, Trichoderma): Can cause liver damage, inflammation, and immune system suppression 4. Fumonisins (Fusarium): Can cause liver damage, cancer, and neurological problems 5. Zearalenone (Fusarium): Can cause liver damage, estrogenic effects, and reproductive issues 6. Deoxynivalenol (Fusarium): Can cause liver damage, inflammation, and immune system suppression 7. T-2 Toxin (Fusarium): Can cause liver damage, inflammation, and immune system suppression 8. HT-2 Toxin (Fusarium): Can cause liver damage, inflammation, and immune system suppression 9. Patulin (Penicillium): Can cause liver damage, kidney damage, and cancer 10. Gliotoxin (Aspergillus): Can cause liver damage, inflammation, and immune system suppression Please note that this list is not exhaustive, and the effects of these toxins can vary depending on the individual, the amount and duration of exposure, and other factors. Additionally, some fungi can produce multiple toxins, and some toxins can have similar effects

Rheumatoid arthritis (RA) is a chronic autoimmune disease that results in swelling, pain & stiffness in the joints…due to the immune system attacking healthy cells. As more research goes into the gut microbiome, there starts to be more potential ‘connections’ between the diversity (or lack thereof) of the gut microbiome & various chronic diseases. Researchers at the University of Leeds, recently concluded a study that tracked potential changes in the gut microbiome of people at risk of developing RA compared to people with RA or those that weren’t at risk of developing RA. There is one ‘telling’ biomarker for RA: CCP+ antibodies in the blood. These antibodies are specific for RA, and the CCP stands for cyclic-cirtullinated protein. These antibodies ‘tag’ healthy cells that the immune system then attacks. What the researchers found is that changes in the gut microbiome could be linked to the onset of clinically evident RA. They found that in the participants that were at risk of developing RA (and did develop RA during the study period) there was a change in the abundance of certain bacteria compared to the those that didn’t have RA. There was a specific strain of Prevotellaceae bacterium that was ‘increased’ (researchers are assuming it is Prevotellaceae copri), but this wasn’t the only one that had a ‘change’ in abundance. Other bacteria that saw a ‘change’ included Alloprevotella strains; Paraprevotella clara, Prevotella stercorea, Prevotellamassilia timonensis, and Prevotella shahii. The researchers did admit that it isn’t clear if the change in these bacteria are the cause or consequence of developing RA…but tracking changes in the microbiome of people at risk of developing RA could help in early detection (as the changes in the microbiome were noted ten months before onset of symptoms), and also the development of personalized treatment plans. #microbiome #antibodies #autoimmunedisorders #rheumatoidarthritis #poopsamples 

This #Arthritis study led by Margaret Harnett at the University of Glasgow examines the immunomodulator ES-62's effects on rheumatoid arthritis in a mouse model. ES-62 restores defective IL-10-producing regulatory B cells (Bregs) and reduces Th1/Th17-driven inflammation, protecting against joint damage. The research links autoimmune arthritis to gut microbiota dysbiosis and weak intestinal barriers. ES-62 prevents joint damage by normalizing gut microbiota and preserving the intestinal barrier. It also balances myeloid/lymphoid cells in the bone marrow, maintaining healthy lymphoid cells and preventing bone- destroying osteoclasts. ES-62's benefits depend on a healthy microbiome. B and T lymphoid cell bone marrow leve ls inversely correlate with joint damage. In contrast, osteoclast progenitor levels positively correlate with joint damage severity in a mouse Collagen-Induced Arthritis Model induced with MD Bioproducts CIA induction reagents. Find out more about the study conducted at the University of Glasgow in collaboration with the University of Strathclyde here: https://lnkd.in/dGdCbyTA Authors: Margaret M. Harnett, James Doonan, Anuradha Tarafdar, Miguel A. Pineda, Josephine Duncombe-Moore, Geraldine Buitrago, Piaopiao Pan, Paul Hoskisson, Selman, Colin and William Harnas. Learn more about the products used in this study: https://lnkd.in/dwEZEneq #Inflammation #Immunology #AutoimmuneDiseases #DrugDiscovery

“Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting multiple organs that is characterized by marked clinical heterogeneity, a fluctuating course with relapses and remissions, and high-titer antibodies to diverse autoantigens.” “Systemic lupus erythematosus (SLE) displays a hallmark interferon (IFN) signature and IFN-I, IFN-II, and IFN-III fluctuate significantly over time in SLE.” “Yet, clinical trials targeting type I IFN (IFN-I) have shown variable efficacy, and blocking IFN-II failed to treat SLE. The researchers show that IFN type levels in SLE vary significantly across clinical and transcriptional endotypes. Evaluating a patient’s elevated interferon combinations allows for a better understanding of how they may react to treatments, and this would allow clinicians to group them into clinical subtypes of lupus.”

Inflammatory diseases affect 5% of the population but we have a poor understanding of how to treat them. Multi-omic studies are changing that. Inflammatory and autoimmune diseases like lupus, psoriasis, Crohn’s disease and ulcerative colitis can be severely debilitating. With respect to the last two, which are inflammatory bowel diseases (IBDs), symptoms can include rectal bleeding, severe abdominal pain, and diarrhea. These conditions are usually diagnosed by looking at inflammatory markers in stool samples or viewing inflamed tissues via colonoscopy or endoscopy. The exact cause of the inflammation in IBD is not well known, although flares in some people can be associated with eating habits or disruptions of the microbiome. This has had the effect of confusing people about the difference between it and irritable bowel syndrome (IBS) which can have similar symptoms but whose cause is more related to infections (like C․diff), bacterial overgrowth, or other changes that affect gut motility. But because IBD is associated with inflammation, and co-occurs frequently with other autoimmune diseases, it’s hypothesized that there is a strong genetic component to the disease. Genome wide association studies (GWAS) have identified over 200 regions of the genome linked to IBD; however, only a few of these regions have mechanistic associations with inflammatory genes. Unfortunately, many of these variants fall in non-coding regions or gene deserts and so it is thought (as is true for much of GWAS) that these associated regions are involved in epigenetic regulation of gene expression in affected cell types. To that end, the researchers behind today’s paper chose to study a region of the genome associated with multiple inflammatory diseases, chromosome 21q22 (chr21q22). In the figure below you can see a) the GWAS association of this region with IBD, primary sclerosing cholangitis (PSC), ankylosing spondylitis (AS) and Takayasu’s arteritis. b) this region is associated with activating H3K27ac epigenetic marks only in inflammatory monocytes. c) this region is physically linked to the ETS2 gene, a transcription factor. d, e, f) CRISPR removal of this region results in downregulation of ETS2 expression. g,h,i,j,k,l) a specific SNP, rs2836882, is associated with recruiting the chromatin remodeling protein PU.1 to this newly discovered ETS2 enhancer. The authors go on to show that CRISPR–Cas9 disruption of ETS2 reduced pro-inflammatory markers and single-cell transcriptomics of diseased IBD tissue confirmed the presence of higher levels of ETS2 in associated monocytes. While more work needs to be done, it appears that targeting the ETS2 pathway presents a promising therapeutic strategy for treating conditions like IBD. ### Stankey CT, et al. 2024. A disease-associated gene desert directs macrophage inflammation through ETS2. Nature. DOI: 10.1038/s41586-024-07501-1 --- Want this in your inbox? Visit my website ⬆️

🎉 Excited to announce our latest research publication! 🎉 Our team has just published a new study on the role of Factor H-related Peptide 1 (FHR1) in Systemic Lupus Erythematosus (SLE) in Frontiers in Immunology. Factor H, a crucial soluble inhibitor of the Complement System, is known for its role in immune regulation. FHR1 can activate the Complement System by competing with Factor H for ligand binding, however the in vivo function of the FHRs is poorly characterized. Our comprehensive analysis of FHR1 and Factor H levels in SLE patients revealed the counterintuitive finding that FHR1 deficiency is associated with a higher susceptibility to SLE. These findings confirm a single previous genetic study and provide new insights that could reshape our understanding of complement system activation in autoimmune diseases. Additionally, we explored the pathogenic role of anti-FH autoantibodies in FHR1-deficient SLE patients and found it to be limited, contrasting with their known impact in atypical hemolytic uremic syndrome (aHUS). This study reflects the collaborative effort and dedication of our incredible research team: Juliane Klehr, Denise Dubler, Laura Infanti, Carlo Chizzolini, Uyen Huynh-Do, MD, MME, Camillo Ribi, and Marten Trendelenburg. Special thanks to the Swiss SLE Cohort Study (SSCS) for providing invaluable patient samples and data. We hope this research opens new avenues for understanding and potentially treating SLE. A big thank you to everyone who supported this project! Read the full paper here: https://lnkd.in/efz3TQ-g #research #SLE #immunology #complementsystem #autoimmunity

🔔 Review Sharing 📚 Rheumatoid arthritis and cardiovascular comorbidities ✒ Authors: Uğur Özkan, Nur Kakilli, Muhammet Gürdoğan, Nurettin Taştekin, Murat Birtane 💡 Rheumatoid arthritis (RA) is the most common rheumatologic disease characterized by inflammation with a definite relationship with heart disease. Impaired immunity, chronic inflammation, genetic susceptibility, autonomic nervous system (ANS) dysfunction, altered metabolic profile have been blamed for ischemic and non-ischemic heart diseases in RA patients. Medications used in RA treatment can also modify the risk of heart diseases by different mechanisms. Understanding the pathogenesis is essential to prevent early cardiac dysfunction in RA patients... ⭐ Keywords: #RheumatoidArthritis, #CardiovascularDisease, #CardiovascularComorbidity, cardiovascular risk factors, epidemiology, exercise, management 🔗 Read the full article: https://lnkd.in/gQTSXKxG 📑 PDF: https://lnkd.in/gqMJEsZU 🔎 This article belongs to our special issue “Comorbidities in rheumatoid arthritis”, edited by Prof. Joan M. Nolla. (https://lnkd.in/gRT24ASv)

𝗛𝗼𝘄 𝗮 “𝗱𝗮𝘁𝗲” 𝗯𝗲𝘁𝘄𝗲𝗲𝗻 𝗶𝗺𝗺𝘂𝗻𝗲 𝗰𝗲𝗹𝗹𝘀 𝗺𝗮𝗸𝗲𝘀 #𝗿𝗵𝗲𝘂𝗺𝗮𝘁𝗶𝘀𝗺 𝗱𝗶𝘀𝗮𝗽𝗽𝗲𝗮𝗿: Dates don’t always work out the way you would like. This is the premise on which scientists at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have developed a new approach towards treating autoimmune diseases. They brought two types of immune cells, B cells and T cells, together at one table – with the result that the T cell killed the B cell. The organizer of this “date” with a dramatic outcome was a medicine named blinatumomab. Killing the B cells responsible for triggering disease led to the disappearance of a severe autoimmune disease, rheumatoid arthritis (also known as rheumatism). Their findings have now been published in the journal Nature Medicine. Normally both B cells and T cells have a key role to play in triggering autoimmune diseases. The FAU team was able to trick the T cells into killing their accomplices, the B cells. This led to a major success in treating rheumatoid arthritis, otherwise known as rheumatism. 𝗠𝗮𝗷𝗼𝗿 𝘀𝘂𝗰𝗰𝗲𝘀𝘀: 𝗡𝗲𝘄 𝗮𝗽𝗽𝗿𝗼𝗮𝗰𝗵 𝗳𝗼𝗿 𝘁𝗿𝗲𝗮𝘁𝗶𝗻𝗴 𝗮𝘂𝘁𝗼𝗶𝗺𝗺𝘂𝗻𝗲 𝗱𝗶𝘀𝗲𝗮𝘀𝗲𝘀: https://lnkd.in/eGgjkfs9 FAU Erlangen-Nürnberg, Georg Schett, Ricardo Grieshaber-Bouyer, Laura Bucci, Tobias Rothe, Maria Gabriella Raimondo, Filippo Fagni, Carlo Tur, Andreas Wirsching, Artur Wilhelm, Stefano Alivernini, Gerhard Krönke, Aline Bozec