This Week in Rheumatology - 2024-11-10

# This Week in Rheumatology ## Rheumatoid Arthritis Recent advancements in rheumatoid arthritis (RA) research highlight innovative therapeutic approaches and deeper insights into the disease's mechanisms. A novel cell therapy using engineered macrophages has been developed to deliver anti-inflammatory drugs directly to inflamed joints, offering a targeted and potentially more effective treatment option. Additionally, a multiscale, mechanistic model of RA has been created to predict therapy responses, particularly for tocilizumab (TCZ) in patients who do not respond to adalimumab (ADA). This model captures the interactions of key immune cells and mediators, providing a valuable tool for drug development and personalized medicine. On the clinical front, a 10-year prospective study found that cervical spine instability in RA patients increased over time, with predictors including hand mutilating changes, longer disease duration, high C-reactive protein (CRP) levels, and previous joint surgery. Another study identified BACH1 as a central regulator of RA fibroblast-like synoviocytes (FLS), suggesting its potential as a therapeutic target. Furthermore, research on G protein-coupled receptor 40 (GPR40) in B cells revealed that its deficiency leads to increased activation, proliferation, and antibody production, contributing to the pathogenesis of RA. Lastly, a systematic literature review explored the interactions between RA and SARS-CoV-2 infection, focusing on immunologic issues, disease management, vaccination, and adverse outcomes. Additionally, a phase III clinical trial demonstrated the efficacy and safety equivalence of CT-P47, a biosimilar of tocilizumab, to the reference drug, including after switching from the reference to the biosimilar. ### References - Engineered self-regulating macrophages for targeted anti-inflammatory drug delivery. by Klimak M, Cimino A, Lenz KL, Springer LE, Collins KH, Harasymowicz NS, Xu N, Pham CTN, Guilak F. Arthritis research & therapy. [PMID: 39501398](https://pubmed.ncbi.nlm.nih.gov/39501398/) - Prevalence and aggravation of cervical spine instabilities in rheumatoid arthritis during over 10 years: a prospective multicenter cohort study. by Kanda Y, Yurube T, Hirata H, Sumi M. Scientific reports. [PMID: 39501065](https://pubmed.ncbi.nlm.nih.gov/39501065/) - Multiscale, mechanistic model of Rheumatoid Arthritis to enable decision making in late stage drug development. by Bedathuru D, Rengaswamy M, Channavazzala M, Ray T, Packrisamy P, Kumar R. NPJ systems biology and applications. [PMID: 39496637](https://pubmed.ncbi.nlm.nih.gov/39496637/) - BACH1 as a key driver in rheumatoid arthritis fibroblast-like synoviocytes identified through gene network analysis. by Pelissier A, Laragione T, Harris C, Rodriguez Martinez M, Gulko PS. Life science alliance. [PMID: 39467637](https://pubmed.ncbi.nlm.nih.gov/39467637/) - Rheumatoid Arthritis and COVID-19 at the Intersection of Immunology and Infectious Diseases: A Related PRISMA Systematic Literature Review. by Vladulescu-Trandafir AI, Bojinca VC, Munteanu C, Anghelescu A, Popescu C, Stoica SI, Aurelian S, Balanescu A, Baetu C, Ciobanu V, Onose G. International journal of molecular sciences. [PMID: 39456932](https://pubmed.ncbi.nlm.nih.gov/39456932/) - Efficacy and safety of CT-P47 versus reference tocilizumab: 32-week results of a randomised, active-controlled, double-blind, phase III study in patients with rheumatoid arthritis, including 8 weeks of switching data from reference tocilizumab to CT-P47. by Smolen JS, Trefler J, Racewicz A, Jaworski J, Zielinska A, Krogulec M, Jeka S, Wojciechowski R, Kolossa K, Dudek A, Krajewska-Wlodarczyk M, Hrycaj P, Klimiuk PA, Burmester GR, Kim S, Bae Y, Yang G, Jung Y, Hong J, Keystone E. RMD open. [PMID: 39424404](https://pubmed.ncbi.nlm.nih.gov/39424404/) - Critical role of G protein-coupled receptor 40 in B cell response and the pathogenesis of rheumatoid arthritis in mice and patients. by Li A, Wang X, Li J, Li X, Wang J, Liu Y, Wang Z, Yang X, Gao J, Wu J, Sun T, Huo L, Yi Y, Shen J, Cai J, Yao Y. Cell reports. [PMID: 39392754](https://pubmed.ncbi.nlm.nih.gov/39392754/) ## Osteoarthritis Recent research in osteoarthritis has uncovered several important findings. Magnusson et al. (2023) identified shared genetic factors between osteoarthritis and cardiovascular disease, suggesting a common etiology that may explain the increased risk of severe cardiovascular events in osteoarthritis patients. In the realm of drug discovery, Coryell et al. (2023) developed a high-throughput screening platform using normal human chondrocytes to identify compounds that inhibit matrix metalloproteinase-13, a key enzyme in the progression of osteoarthritis. Machine learning models, as explored by Castagno et al. (2023), show promise in predicting osteoarthritis progression, although their clinical applicability is currently limited by certain constraints. In clinical treatments, Frydendal et al. (2023) found that total hip replacement provided superior pain relief and functional improvement compared to resistance training in patients with severe hip osteoarthritis. Bliddal et al. (2023) demonstrated that once-weekly semaglutide, a medication originally used for obesity, significantly reduced body weight and knee pain in patients with knee osteoarthritis. Regarding platelet-rich plasma (PRP) injections, Boffa et al. (2023) and Romandini et al. (2023) found that platelet concentration influences the clinical outcomes of PRP injections, while the presence of leukocytes does not affect their safety or efficacy. ### References - Shared genetic factors between osteoarthritis and cardiovascular disease may underlie common etiology. by Magnusson K, Turkiewicz A, Dell'Isola A, Englund M. Nature communications. [PMID: 39500867](https://pubmed.ncbi.nlm.nih.gov/39500867/) - A novel small molecule screening assay using normal human chondrocytes toward osteoarthritis drug discovery. by Coryell PR, Hardy PB, Chubinskaya S, Pearce KH, Loeser RF. PloS one. [PMID: 39485774](https://pubmed.ncbi.nlm.nih.gov/39485774/) - Understanding the role of machine learning in predicting progression of osteoarthritis. by Castagno S, Gompels B, Strangmark E, Robertson-Waters E, Birch M, van der Schaar M, McCaskie AW. The bone & joint journal. [PMID: 39481441](https://pubmed.ncbi.nlm.nih.gov/39481441/) - Total Hip Replacement or Resistance Training for Severe Hip Osteoarthritis. by Frydendal T, Christensen R, Mechlenburg I, Mikkelsen LR, Varnum C, Graversen AE, Kjaersgaard-Andersen P, Revald PH, Hofbauer C, Bieder MJ, Qassim H, Munir MS, Jakobsen SS, Nielsen SM, Ingwersen KG, Overgaard S. The New England journal of medicine. [PMID: 39476341](https://pubmed.ncbi.nlm.nih.gov/39476341/) - Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. by Bliddal H, Bays H, Czernichow S, Udden Hemmingsson J, Hjelmesaeth J, Hoffmann Morville T, Koroleva A, Skov Neergaard J, Velez Sanchez P, Wharton S, Wizert A, Kristensen LE. The New England journal of medicine. [PMID: 39476339](https://pubmed.ncbi.nlm.nih.gov/39476339/) - Influence of Platelet Concentration on the Clinical Outcome of Platelet-Rich Plasma Injections in Knee Osteoarthritis. by Boffa A, De Marziani L, Andriolo L, Di Martino A, Romandini I, Zaffagnini S, Filardo G. The American journal of sports medicine. [PMID: 39397728](https://pubmed.ncbi.nlm.nih.gov/39397728/) - Leukocytes Do Not Influence the Safety and Efficacy of Platelet-Rich Plasma Injections for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Controlled Trial. by Romandini I, Boffa A, Di Martino A, Andriolo L, Cenacchi A, Sangiorgi E, Orazi S, Pizzuti V, Zaffagnini S, Filardo G. The American journal of sports medicine. [PMID: 39394763](https://pubmed.ncbi.nlm.nih.gov/39394763/) ## Other Rheumatic Diseases Recent research in other rheumatic diseases has shed light on various aspects of diagnosis, treatment, and symptom management. In fibromyalgia, a randomized controlled trial demonstrated that functional exercise training significantly reduced pain and improved quality of life compared to stretching exercises. Additionally, a study on muscle oxygen saturation in fibromyalgia patients revealed substantial alterations in oxygen utilization within muscle fibers, which may contribute to chronic pain and severe fatigue. These findings suggest that targeted therapeutic approaches focusing on muscle oxygenation could potentially alleviate symptoms and enhance the quality of life for fibromyalgia patients. In the context of Behcet's syndrome, a study comparing infliximab and cyclophosphamide for severe cases found that infliximab had a superior complete response rate and fewer adverse events, highlighting its potential as a preferred treatment option. For juvenile idiopathic arthritis, a new pediatric ultrasound protocol (PIUS-knee) was developed to detect knee arthritis, showing high sensitivity for synovitis. This protocol could improve early diagnosis and management in pediatric patients. Lastly, imaging modalities such as MRI, ultrasound, and PET scans have been shown to play a crucial role in diagnosing and managing myositis, while a novel CAR T cell therapy using suppressive regulatory T cells has been proposed for treating multiple sclerosis, offering a promising new approach in the field of rheumatology. ### References - Detection and management of autoimmune disease-associated interstitial lung diseases. by Esposito AJ, Ajam A. The American journal of managed care. [PMID: 39495031](https://pubmed.ncbi.nlm.nih.gov/39495031/) - A functional exercise program improves pain and health related quality of life in patients with fibromyalgia: a randomized controlled trial. by Fernandes G, Nery M, Meireles SM, Santos R, Natour J, Jennings F. Advances in rheumatology (London, England). [PMID: 39449056](https://pubmed.ncbi.nlm.nih.gov/39449056/) - Infliximab versus Cyclophosphamide for Severe Behcet's Syndrome. by Saadoun D, Maalouf G, Vieira M, Trad S, Lazaro E, Sacre K, Plessier A, Sene T, Kone-Paut I, Noel N, Mekinian A, Lambert M, Ribeiro E, Mirault T, Mele N, Dellal A, Fain O, Melki I, Chiche L, Gaudric J, Redheuil A, Maillart E, Ghembaza A, Desbois AC, Mirouse A, Domont F, Leroux G, Ferfar Y, Rigolet A, Viallard JF, Vautier M, Resche-Rigon M, Cacoub P. NEJM evidence. [PMID: 39437137](https://pubmed.ncbi.nlm.nih.gov/39437137/) - Unveiling the link: exploring muscle oxygen saturation in fibromyalgia and its implications for symptomatology and therapeutic strategies. by Rubio-Zarapuz A, Parraca JA, Tornero-Aguilera JF, Clemente-Suarez VJ. Medical gas research. [PMID: 39436169](https://pubmed.ncbi.nlm.nih.gov/39436169/) - Development and validation of a pediatric internationally agreed ultrasound knee synovitis protocol (PIUS-knee) by the PReS imaging working party. by Windschall D, Trauzeddel R, Gohar F, Adiguzel-Dundar H, Hardt S, Krumrey-Langkammerer M, Fotis L, Berendes R, Schua S, Haller M, Demir F, Sozeri B, Magni-Manzoni S. Pediatric rheumatology online journal. [PMID: 39434153](https://pubmed.ncbi.nlm.nih.gov/39434153/) - MOG-specific CAR Tregs: a novel approach to treat multiple sclerosis. by Frikeche J, David M, Mouska X, Treguer D, Cui Y, Rouquier S, Lecorgne E, Proics E, Fall PB, Lafon A, Lara G, Menardi A, Fenard D, Abel T, Gertner-Dardenne J, de la Rosa M, Dumont C. Journal of neuroinflammation. [PMID: 39428507](https://pubmed.ncbi.nlm.nih.gov/39428507/) - Imaging Modalities in Myositis: A Clinical Review. by Yoshida T, Albayda J. Rheumatic diseases clinics of North America. [PMID: 39415372](https://pubmed.ncbi.nlm.nih.gov/39415372/) ## Immunology Celiac disease (CD) is an autoimmune disorder characterized by intestinal inflammation and damage in response to gluten ingestion in genetically susceptible individuals. The current standard treatment is a strict, lifelong gluten-free diet, which is often challenging to adhere to. Recent research has focused on developing novel pharmacologic strategies to provide more effective and manageable treatment options. These innovations include transglutaminase inhibitors, which prevent the modification of gluten peptides, and nanoparticle-based therapies that recalibrate the immune response. These therapies aim to improve patient outcomes and quality of life by reducing the burden of dietary restrictions. In parallel, the study of immune-mediated glomerulonephritis has highlighted the critical role of epitope spreading in the progression of autoimmune diseases such as membranous nephropathy, lupus nephritis, and ANCA-associated vasculitis. Epitope spreading refers to the expansion of the immune response from the initial target to additional antigens, contributing to the complexity and severity of these conditions. Understanding these immunological mechanisms is crucial for the development of targeted therapies that can effectively manage and potentially cure autoimmune disorders. The integration of these advances in both CD and glomerulonephritis underscores the importance of continued research and multidisciplinary collaboration to improve patient care. ### References - Beyond the gluten-free diet: Innovations in celiac disease therapeutics. by Massironi S, Franchina M, Elvevi A, Barisani D. World journal of gastroenterology. [PMID: 39493330](https://pubmed.ncbi.nlm.nih.gov/39493330/) - Epitope Spreading in Immune-Mediated Glomerulonephritis: The Expanding Target. by Strizzi CT, Ambrogio M, Zanoni F, Bonerba B, Bracaccia ME, Grandaliano G, Pesce F. International journal of molecular sciences. [PMID: 39456878](https://pubmed.ncbi.nlm.nih.gov/39456878/) ## Systemic Lupus Erythematosus Systemic Lupus Erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, affecting multiple organs with varying clinical presentations and disease severity. Recent research highlights the significant role of proinflammatory type I interferons (IFN-I) in SLE, particularly in lupus nephritis. IFN-I contributes to the development and immunopathogenesis of SLE, and while therapies targeting IFN-I and its downstream signaling molecules show promise, some findings challenge their therapeutic benefits, especially in lupus nephritis. Circulatory microRNAs, such as miR-199a, have emerged as independent predictors of lupus nephritis and may serve as diagnostic biomarkers. B cell-targeting biologics, including those that inhibit B cell maturation antigen (BCMA) and its ligands BAFF and APRIL, have shown effectiveness and safety in treating lupus nephritis. BCMA expression is significantly increased in SLE patients, correlating with plasmablast frequencies, serum anti-dsDNA antibodies, and complement consumption, making it a potential biomarker and therapeutic target. The CD154/CD40 dyad, a key participant in SLE pathogenesis, is overexpressed in T and B lymphocytes, contributing to disease development. Therapeutic strategies targeting this dyad have shown promise in animal models and human studies, although concerns over thromboembolic complications have led to the development of second-generation antibodies. Lastly, the secretion of CCL2 by dendritic cells has been implicated in blood-brain barrier disruption, leading to cognitive impairment in patients with neuropsychiatric SLE (NPSLE). ### References - Therapeutically targeting proinflammatory type I interferons in systemic lupus erythematosus: efficacy and insufficiency with a specific focus on lupus nephritis. by Lai B, Luo SF, Lai JH. Frontiers in immunology. [PMID: 39478861](https://pubmed.ncbi.nlm.nih.gov/39478861/) - Systemic lupus erythematosus: pathogenesis and targeted therapy. by Su X, Yu H, Lei Q, Chen X, Tong Y, Zhang Z, Yang W, Guo Y, Lin L. Molecular biomedicine. [PMID: 39472388](https://pubmed.ncbi.nlm.nih.gov/39472388/) - Circulatory microRNAs and proinflammatory cytokines as predictors of lupus nephritis. by ElFeky DS, Omar NM, Shaker OG, Abdelrahman W, Gheita TA, Nada MG. Frontiers in immunology. [PMID: 39464895](https://pubmed.ncbi.nlm.nih.gov/39464895/) - Effectiveness and safety of B cell-targeting biologics in the treatment of lupus nephritis: a systematic review and network meta‑analysis. by Zhao X, Yang SQ, Li M, Wang YG. Renal failure. [PMID: 39440406](https://pubmed.ncbi.nlm.nih.gov/39440406/) - B-Cell Maturation Antigen (BCMA) as a Biomarker and Potential Treatment Target in Systemic Lupus Erythematosus. by Martin J, Cheng Q, Laurent SA, Thaler FS, Beenken AE, Meinl E, Kronke G, Hiepe F, Alexander T. International journal of molecular sciences. [PMID: 39409173](https://pubmed.ncbi.nlm.nih.gov/39409173/) - Implications of CD154 and Its Receptors in the Pathogenesis and Treatment of Systemic Lupus Erythematosus. by Allard CC, Salti S, Mourad W, Hassan GS. Cells. [PMID: 39404385](https://pubmed.ncbi.nlm.nih.gov/39404385/) - Unlocking the secrets of NPSLE: the role of dendritic cell-secreted CCL2 in blood-brain barrier disruption. by Wang L, Zheng G, Wang P, Jia X. Frontiers in immunology. [PMID: 39403387](https://pubmed.ncbi.nlm.nih.gov/39403387/) ## Vasculitis Vasculitis, a group of disorders characterized by inflammation of blood vessels, presents significant diagnostic and therapeutic challenges due to its complexity and variability. Primary central nervous system vasculitis (PCNSV) is a particularly rare and intricate form of vasculitis that poses formidable diagnostic and therapeutic hurdles. Recent research emphasizes the need for a multidisciplinary approach to manage PCNSV, including the use of advanced imaging techniques and tailored treatment regimens. In addition to the central nervous system, vasculitis can affect other critical organs, such as the heart. Patients with systemic vasculitides are at a heightened risk of developing coronary artery disease (CAD) due to the inflammatory processes that contribute to accelerated atherosclerosis and myocardial ischemia. Managing CAD in these patients requires a comprehensive strategy that includes regular monitoring, risk factor modification, and targeted interventions to prevent complications. Vascular imaging plays a crucial role in the evaluation and management of large-vessel vasculitis (LVV), a condition that affects major arteries. Recent advancements in imaging techniques have improved the accuracy of diagnosis and the monitoring of disease progression, but challenges remain in standardizing imaging protocols and interpreting results. Overall, the latest research underscores the importance of a multidisciplinary approach and the integration of advanced imaging and tailored treatments in managing the diverse manifestations of vasculitis. ### References - Primary CNS Vasculitis - A Focussed Review on Treatment. by Kesav P, Raj DM, Hajj-Ali RA, Hussain SI, John S. Vascular health and risk management. [PMID: 39469466](https://pubmed.ncbi.nlm.nih.gov/39469466/) - Management of Coronary Artery Diseases in Systemic Vasculitides: Complications and Strategies. by Shumnalieva R, Mileva N, Padjen I, Siliogkas P, Chervenkov L, Bakopoulou K, Kaouri IE, Vasilska A, Miteva D, Vassilev D, Velikova T. Medicina (Kaunas, Lithuania). [PMID: 39459361](https://pubmed.ncbi.nlm.nih.gov/39459361/) - Imaging Challenges and Developments in Large-vessel Vasculitis. by Matza MA, Arevalo AB, Unizony S. Rheumatic diseases clinics of North America. [PMID: 39415370](https://pubmed.ncbi.nlm.nih.gov/39415370/) ## Biologics The latest research in the field of biologics has explored both the optimization of drug administration and the underlying mechanisms of disease response. A recent clinical practice guideline, published in the BMJ, evaluated the role of proactive therapeutic drug monitoring (TDM) in adult patients with inflammatory bowel disease, inflammatory arthritis, or psoriasis. The guideline panel issued weak recommendations for or against proactive TDM for intravenous infliximab and adalimumab during both maintenance and induction phases of treatment. This suggests that while TDM may offer some benefits, its overall impact on patient outcomes remains uncertain. In a related study published in RMD Open, researchers investigated the association between disease response in rheumatoid arthritis and changes in paraoxonase-1 (PON1) activity and oxylipins across four classes of biologic therapies. The study found that improvements in disease activity were linked to enhanced PON1 activity, which has significant implications for cardiovascular safety. Together, these findings highlight the complex interplay between biologic drug monitoring and the biological mechanisms that drive therapeutic responses, underscoring the need for personalized approaches to optimize treatment outcomes in inflammatory diseases. ### References - Proactive therapeutic drug monitoring of biologic drugs in adult patients with inflammatory bowel disease, inflammatory arthritis, or psoriasis: a clinical practice guideline. by Kawano-Dourado L, Kristianslund EK, Zeraatkar D, Jani M, Makharia G, Hazlewood G, Smith C, Jess T, Stabell C, Schatten A, Owen A, Gehin J, Katsidzira L, Weinberg D, Bauer-Ventura I, Tugwell P, Moayyedi P, Cecchi AVW, Shimabuco A, Seterelv S, Gyuatt G, Agoritsas T, Vandvik PO. BMJ (Clinical research ed.). [PMID: 39467592](https://pubmed.ncbi.nlm.nih.gov/39467592/) - Disease response in rheumatoid arthritis across four biologic therapies associates with improvement in paraoxonase-1 activity and oxylipins. by Razmjou AA, Kremer JM, Pappas DA, Curtis JR, Wang J, Shahbazian A, Elashoff DA, Guo R, Meriwether D, Sulaiman D, O'Connor E, Reddy ST, Charles-Schoeman C. RMD open. [PMID: 39461874](https://pubmed.ncbi.nlm.nih.gov/39461874/) ## Ankylosing Spondylitis Recent research in Ankylosing Spondylitis (AS) and related spondyloarthritis (SpA) has shed light on various aspects of the disease, from symptom progression to extra-articular manifestations and diagnostic imaging. A study by Bento da Silva et al. (2023) found that patients with early axial spondyloarthritis showed greater improvements in spinal symptoms and mobility over a 2-year period compared to those with non-axial spondyloarthritis chronic back pain. This suggests that early diagnosis and intervention may be particularly beneficial for axial spondyloarthritis patients. Another review by Toufik et al. (2023) focused on the prevalence and characteristics of acute anterior uveitis, the most common extra-articular feature of SpA. The review highlighted that uveitis is more prevalent in SpA patients who are HLA-B27 positive and discussed the clinical manifestations and therapeutic management of this condition. Lastly, Mohan and Hwang (2023) emphasized the critical role of imaging in diagnosing and predicting treatment outcomes in axial spondyloarthritis, underscoring the importance of advanced imaging techniques in the management of the disease. Together, these studies provide a comprehensive overview of the current understanding of AS and SpA, highlighting the need for early intervention, comprehensive management of extra-articular manifestations, and the use of advanced imaging in diagnosis and treatment planning. ### References - Baseline and 2-year differences in spinal symptoms and spinal and hip mobility in early axial spondyloarthritis and non-axial spondyloarthritis chronic back pain patients. by Bento da Silva A, Ramiro S, van Lunteren M, Marques ML, van de Sande M, Fongen C, Exarchou S, Ramonda R, van der Heijde D, van Gaalen FA. RMD open. [PMID: 39461873](https://pubmed.ncbi.nlm.nih.gov/39461873/) - Spondyloarthritis Associated with Uveitis: A Review. by Toufik H, Ghassem MA, Majjad A, Mounach A, Bezza A. Middle East African journal of ophthalmology. [PMID: 39444995](https://pubmed.ncbi.nlm.nih.gov/39444995/) - Axial Imaging in Spondyloarthritis. by Mohan V, Hwang MC. Rheumatic diseases clinics of North America. [PMID: 39415369](https://pubmed.ncbi.nlm.nih.gov/39415369/) ## Scleroderma Recent research in Scleroderma, or systemic sclerosis (SSc), has shed light on both therapeutic approaches and the underlying genetic mechanisms of the disease. In one study, Komura (2023) highlights the potential of B cell-targeted therapies, such as Uplizna((R)) (inebilizumab), which targets a broader range of B cells and has shown promise in improving symptoms of skin and lung disease. This approach leverages the role of B cells in the immune response, which is known to be dysregulated in SSc. Concurrently, Vijayraghavan et al. (2023) delve into the genetic and mutational landscape of SSc, revealing widespread mutagenesis and chromosomal instability in the somatic genomes of affected individuals. Their findings suggest that the chronic inflammation and immune response associated with SSc can trigger DNA damage, leading to elevated mutation rates and the presence of mutation signatures typically seen in cancer genomes. These genetic changes, including somatic hypermutation and kataegis, may not only contribute to the progression of SSc but also influence the effectiveness of B cell-targeted therapies. Understanding these genetic alterations could provide valuable insights into the development of more personalized and effective treatment strategies for SSc. ### References - CD19: a promising target for systemic sclerosis. by Komura K. Frontiers in immunology. [PMID: 39421745](https://pubmed.ncbi.nlm.nih.gov/39421745/) - Widespread mutagenesis and chromosomal instability shape somatic genomes in systemic sclerosis. by Vijayraghavan S, Blouin T, McCollum J, Porcher L, Virard F, Zavadil J, Feghali-Bostwick C, Saini N. Nature communications. [PMID: 39406724](https://pubmed.ncbi.nlm.nih.gov/39406724/) ## Genetics Recent research in genetics has shed light on the role of somatic mutations in the development of autoinflammatory and autoimmune diseases. According to a study published in Nature Reviews Rheumatology, somatic mutations are increasingly recognized as common, age-related processes that occur in all cells throughout the body. These mutations contribute to the pathogenesis of both complex and monogenic immunological diseases, highlighting their significance in the genetic landscape of these conditions. Understanding the mechanisms by which somatic mutations influence disease development is crucial for advancing our knowledge of the genetic basis of autoinflammatory and autoimmune disorders, and may pave the way for new therapeutic strategies. ### References - Somatic mutations in autoinflammatory and autoimmune disease. by Torreggiani S, Castellan FS, Aksentijevich I, Beck DB. Nature reviews. Rheumatology. [PMID: 39394526](https://pubmed.ncbi.nlm.nih.gov/39394526/)