المؤلفون: Wen Zhu, Alanya J. Nardone, Lucciano A. Pearce

المصدر: Frontiers in Chemical Biology, Vol 3 (2024)

مصطلحات موضوعية: GMP synthetase, CTP synthetase, asparagine synthetase, NAD+ synthetase, FGAS, carbamoyl phosphatase synthetase, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Bifunctional enzymes, characterized by their dual active sites, enable efficient chemical conversion and substrate channeling using elegant coupling mechanisms to coordinate the two active sites. In humans, several bifunctional enzymes synthesize de novo carbon-nitrogen bonds by hydrolyzing glutamine and ATP in distinct active sites. Notable examples include guanosine monophosphate synthetase, cytidine triphosphate synthetase, phosphoribosylformyl-glycinamidine synthase, asparagine synthetase, and nicotinamide adenine dinucleotide synthetase. A more complex example of multifunctional glutamine-hydrolyzing synthetases in humans is carbamoyl phosphate synthetase. These enzymes are crucial for the biosynthesis of amino acids, nucleic acids, and co-factors, thereby playing pivotal roles in human health. This review delineates recent progress in understanding the structural characteristics, regulatory mechanisms, and disease relevance of glutamine-hydrolyzing synthetases in humans. Insights into their catalysis and activity regulation offer potential pathways for developing novel therapeutics.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fchbi.2024.1410435/fullTest; https://doaj.org/toc/2813-530XTest

الوصول الحر: https://doaj.org/article/42644666b67e4367ad1434d0f5b9e510Test

المؤلفون: Giuseppe Carlo Iorio, Nerina Denaro, Lorenzo Livi, Isacco Desideri, Valerio Nardone, Umberto Ricardi

المصدر: Frontiers in Oncology, Vol 14 (2024)

مصطلحات موضوعية: HNC (head and neck cancer), radiotherapy, radiation oncology, cancer care, personalized oncology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2024.1437237/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/b062b8ebbb45481fb05450797817f508Test

المؤلفون: Olga Maria Nardone, Giulio Calabrese, Alessia La Mantia, Rossella Caso, Anna Testa, Fabiana Castiglione

المصدر: Frontiers in Medicine, Vol 11 (2024)

مصطلحات موضوعية: disability, holistic care, bowel urgency, fatigue, sexual dysfunction, fertility, Medicine (General), R5-920

الوصف: In recent years, the concept of disability has increasingly garnered attention as a crucial long-term target of inflammatory bowel disease (IBD) management. The treatment paradigm has changed dramatically from full control of the disease (clinical and endoscopic remission) toward physical and emotional well-being with the goal of preventing disability and normalizing quality of life. However, in certain cases, despite achieving good disease control, patients may still experience symptoms associated with disability, and reduced emotional wellness. These symptoms can significantly impact various biopsychosocial factors, including interpersonal relationships, educational or work-related activities, body image, and sexual functioning. Nevertheless, they often remain overlooked in the context of IBD care. In this narrative review, we aim to shed light on the burden of certain disability-related symptoms such as bowel urgency, sexual dysfunction, impaired fertility and fatigue, emphasizing the importance of acknowledging and validating them in a clinical setting. There is a demanding need for comprehensive care for IBD patients, with IBD clinicians being mindful of the psychosocial challenges faced by their patients. Providing timely and appropriate management of these challenges alongside IBD treatment is key to achieving holistic remission and enhancing the overall quality of life while reducing disability.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmed.2024.1416054/fullTest; https://doaj.org/toc/2296-858XTest

الوصول الحر: https://doaj.org/article/cb94cbfc6d40451dac619c68bd518600Test

المؤلفون: Vanessa N. Frey, Patrick B. Langthaler, Nora Renz, Georg Zimmermann, Christopher Höhn, Kerstin Schwenker, Aljoscha Thomschewski, Alexander B. Kunz, Yvonne Höller, Raffaele Nardone, Eugen Trinka

المصدر: Frontiers in Medical Technology, Vol 6 (2024)

مصطلحات موضوعية: movement preparation, paraplegia, physical activity, transcranial magnetic stimulation, cortical excitability, Medical technology, R855-855.5

الوصف: BackgroundPatients with spinal cord injury (SCI) show abnormal cortical excitability that might be caused by deafferentation. We hypothesize a reduced short-interval intracortical inhibition preceding movement in patients with SCI compared with healthy participants. In addition, we expect that neuroplasticity induced by different types of sports can modulate intracortical inhibition during movement preparation in patients with SCI.MethodsWe used a reaction test and paired-pulse transcranial magnetic stimulation to record cortical excitability, assessed by measuring amplitudes of motor-evoked potentials in preparation of movement. The participants were grouped as patients with SCI practicing wheelchair dancing (n = 7), other sports (n = 6), no sports (n = 9), and healthy controls (n = 24).ResultsThere were neither significant differences between healthy participants and the patients nor between the different patient groups. A non-significant trend (p = .238), showed that patients engaged in sports have a stronger increase in cortical excitability compared with patients of the non-sportive group, while the patients in the other sports group expressed the highest increase in cortical excitability.ConclusionThe small sample sizes limit the statistical power of the study, but the trending effect warrants further investigation of different sports on the neuroplasticity in patients with SCI. It is not clear how neuroplastic changes impact the sensorimotor output of the affected extremities in a patient. This needs to be followed up in further studies with a greater sample size.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmedt.2024.1297552/fullTest; https://doaj.org/toc/2673-3129Test

الوصول الحر: https://doaj.org/article/5fbb0d2f36ef47dfa9ac7ea5c70907f0Test

المؤلفون: Vito Longo, Carminia Maria Della Corte, Alessandro Russo, Francesca Spinnato, Francesca Ambrosio, Riccardo Ronga, Antonella Marchese, Teresa Del Giudice, Concetta Sergi, Francesca Casaluce, Marina Gilli, Michele Montrone, Valerio Gristina, Vincenzo Sforza, Maria Lucia Reale, Raimondo Di Liello, Alberto Servetto, Helga Lipari, Claudio Longhitano, Laura Vizzini, Anna Manzo, Antonella Cristofano, Loretta Paolelli, Annalisa Nardone, Simona De Summa, Antonella Perrone, Carmela Bisceglia, Caterina Derosa, Valerio Nardone, Giuseppe Viscardi, Domenico Galetta, Fabiana Vitiello

المصدر: Frontiers in Immunology, Vol 14 (2024)

مصطلحات موضوعية: consolidative radiotherapy, SCLC - small cell lung cancer, chemoimmunotherapy, innate immunity, safety, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundConsolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented.MethodsA total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy.ResultsPreclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1289434/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/0916d9972ccf47d690c1cb596c1e055dTest

المؤلفون: Patrizia Ciammella, Salvatore Cozzi, Paolo Borghetti, Marco Galaverni, Valerio Nardone, Maria Paola Ruggieri, Matteo Sepulcri, Vieri Scotti, Alessio Bruni, Francesca Zanelli, Roberto Piro, Elena Tagliavini, Andrea Botti, Federico Iori, Emanuele Alì, Chiara Bennati, Marcello Tiseo

المصدر: Frontiers in Oncology, Vol 14 (2024)

مصطلحات موضوعية: locally advanced non-small cell lung cancer, chemo-radiation, PD-L1 expression, PD-L1 negative patients, re-biopsy, durvalumab, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: BackgroundChemoradiation therapy (CRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CRT on tumor cells programmed cell death ligand-1 (PD-L1) expression is unknown.MethodsIn this multicentric retrospective study, we analyzed paired NSCLC specimens that had been obtained pre- and post-CRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. The purpose of this study was to evaluate the feasibility, risk of complications, and clinical relevance of performing re-biopsy after CRT in patients with PD-L1 negative LA-NSCLC.ResultsOverall, 31 patients from 6 centers with PD-L1 negative LA-NSCLC were analyzed. The percentage of tumor cells with PD-L1 expression significantly increased between pre- and post-CRT specimens in 14 patients (45%). Nine patients had unchanged PD-L1 expression after CRT, in five patients the rebiopsy material was insufficient for PD-L1 analysis and in two patients no tumor cells at rebiopsy were found. The post-rebiopsy complication rate was very low (6%). All patients with positive PD-L1 re-biopsy received Durvalumab maintenance after CRT, except one patient who had a long hospitalization for tuberculosis reactivation. Median PFS of patients with unchanged or increased PD-L1 expression was 10 and 16.9 months, respectively.ConclusionCRT administration can induce PD-L1 expression in a considerable fraction of PD-L1 negative patients at baseline, allowing them receiving the maintenance Durvalumab in Europe. Hence, after a definitive CRT, PD-L1 redetermination should be considered in patients with LA-NSCLC PD-L1 negative, to have a better selection of maintenance Durvalumab candidates.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2024.1325249/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/5295884ae5854ba4ba4dd0e47e0a1c72Test

المؤلفون: Patrizia Catellani, Marco Biella, Valentina Carfora, Antonio Nardone, Luca Brischigiaro, Marina Rita Manera, Marco Piastra

المصدر: Frontiers in Psychology, Vol 14 (2023)

مصطلحات موضوعية: physical activity, message intervention, framing, regulatory focus, artificial intelligence, Psychology, BF1-990

الوصف: ObjectiveWe investigated how physical activity can be effectively promoted with a message-based intervention, by combining the explanatory power of theory-based structural equation modeling with the predictive power of data-driven artificial intelligence.MethodsA sample of 564 participants took part in a two-week message intervention via a mobile app. We measured participants’ regulatory focus, attitude, perceived behavioral control, social norm, and intention to engage in physical activity. We then randomly assigned participants to four message conditions (gain, non-loss, non-gain, loss). After the intervention ended, we measured emotions triggered by the messages, involvement, deep processing, and any change in intention to engage in physical activity.ResultsData analysis confirmed the soundness of our theory-based structural equation model (SEM) and how the emotions triggered by the messages mediated the influence of regulatory focus on involvement, deep processing of the messages, and intention. We then developed a Dynamic Bayesian Network (DBN) that incorporated the SEM model and the message frame intervention as a structural backbone to obtain the best combination of in-sample explanatory power and out-of-sample predictive power. Using a Deep Reinforcement Learning (DRL) approach, we then developed an automated, fast-profiling strategy to quickly select the best message strategy, based on the characteristics of each potential respondent. Finally, the fast-profiling method was integrated into an AI-based chatbot.ConclusionCombining the explanatory power of theory-driven structural equation modeling with the predictive power of data-driven artificial intelligence is a promising strategy to effectively promote physical activity with message-based interventions.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fpsyg.2023.1200304/fullTest; https://doaj.org/toc/1664-1078Test

الوصول الحر: https://doaj.org/article/e6b2f060389e4beb984cfda51f87a4d4Test

المؤلفون: Giuseppe Giovanni Nardone, Beatrice Spedicati, Maria Pina Concas, Aurora Santin, Anna Morgan, Lorenzo Mazzetto, Maurizio Battaglia-Parodi, Giorgia Girotto

المصدر: Frontiers in Genetics, Vol 14 (2023)

مصطلحات موضوعية: color vision defects, Deutan, Protan, Tritan, genome wide association study, genetic isolates, Genetics, QH426-470

الوصف: Introduction: Color vision defects (CVDs) are conditions characterized by the alteration of normal trichromatic vision. CVDs can arise as the result of alterations in three genes (OPN1LW, OPN1MW, OPN1SW) or as a combination of genetic predisposition and environmental factors. To date, apart from Mendelian CVDs forms, nothing is known about multifactorial CVDs forms.Materials and Methods: Five hundred and twenty individuals from Silk Road isolated communities were genotyped and phenotypically characterized for CVDs using the Farnsworth D-15 color test. The CVDs traits Deutan-Protan (DP) and Tritan (TR) were analysed. Genome Wide Association Study for both traits was performed, and results were corrected with a False Discovery Rate linkage-based approach (FDR-p). Gene expression of final candidates was investigated using a published human eye dataset, and pathway analysis was performed.Results: Concerning DP, three genes: PIWIL4 (FDR-p: 9.01*10–9), MBD2 (FDR-p: 4.97*10–8) and NTN1 (FDR-p: 4.98*10–8), stood out as promising candidates. PIWIL4 is involved in the preservation of Retinal Pigmented Epithelium (RPE) homeostasis while MBD2 and NTN1 are both involved in visual signal transmission. With regards to TR, four genes: VPS54 (FDR-p: 4.09*10–9), IQGAP (FDR-p: 6,52*10–10), NMB (FDR-p: 8.34*10–11), and MC5R (FDR-p: 2.10*10–8), were considered promising candidates. VPS54 is reported to be associated with Retinitis pigmentosa; IQGAP1 is reported to regulate choroidal vascularization in Age-Related Macular Degeneration; NMB is involved in RPE homeostasis regulation; MC5R is reported to regulate lacrimal gland function.Discussion: Overall, these results provide novel insights regarding a complex phenotype (i.e., CVDs) in an underrepresented population such as Silk Road isolated communities.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fgene.2023.1161696/fullTest; https://doaj.org/toc/1664-8021Test

الوصول الحر: https://doaj.org/article/4b0714f7de2c4bca80ef9878c948145eTest

المؤلفون: Luigi Marano, Federica Marmorino, Isacco Desideri, Ludovico Carbone, Alessandro Rizzo, Viola Salvestrini, Franco Roviello, Saverio Cinieri, Vittorio Donato, Raffaele De Luca, NutriOnc Research Group, Silvia Sofia, Marco Milone, Benedetto Ielpo, Maria Teresa Mita, Silvia Ministrini, Mario Giuffrida, Roberta Tutino, Caterina Baldi, Giampaolo Perri, Anna Stella Lippolis, Chiara Marafante, Giusy Giannandrea, Marco Vito Marino, Letizia Laface, Salomone Di Saverio, Luca Aldrighetti, Nicola de’Angelis, Nick Salimian, Marco Caricato, Gianluca Pellino, Sara Vertaldi, Federica Cipriani, Gabriella Teresa Capolupo, Antonio Costanzo, Letizia Santandrea, Gaetano Gallo, Andrea Belli, Laura Mastrangelo, Fausto Rosa, Nicolò Pecorelli, Graziella Marino, Alessio Giordano, Nicola Cillara, Maria Lemma, Francesco Pata, Federico Cammillini, Gianmario Edoardo Poto, Giulia Grassi, Donato Francesco Altomare, Arcangelo Picciariello, Lorenzo Petagna, Luca Ippolito, Elio Treppiedi, Daniele Delogu, Abdallah Moukachar, Stefano Granieri, Giuseppe Cuticone, Osvaldo Carpineto Samorani, Daniela Rega, Leonardo Solaini, Stefano de Pascale, Francesca Ascari, Michele Manigrasso, Simona Badalucco, Salvatore Paiella, Sara Coppola, Roberta Iadarola, Giovanna Di Meo, Isacco Montroni, Fabio Vistoli, Valentina Ferraro, Edoardo Saladino, Federico Fazio, Roberta Rota, Francesco Orlando, Simone Famularo, Cinzia Bizzoca, Giorgio Dalmonte, Marco Inama, Luigi Verre, Leandro Siragusa, Casoni Pattacini Gianmaria, Michele Benedetti, Nicolò Tamini, Cristian Conti, Giorgio Ammerata, Serena Mantova, Vito Leonardo Pinto, Arianna Corvasce, Giorgio Micheletti, Teresa Perra, Marco Pellicciaro, Marco Materazzo, Michele Zuolo, Emanuele Doria, Antonio Brillantino, Luca Del Prete, Andrea Muratore, Claudio Luciani, Giulia Turri, Fabio Casciani, Giuliani Giuseppe, Graziana Barile, Oldrà Gaia, Valeria Restaino, Simona Deidda, Michele Ammendola, Andrea Fares Bucci, Patrizia Marsanic, Dario Cassetti, Luca Resca, Daniele Fusario, Eleonora Andreucci, Anna Michelotti, Brunella Amoruso, Isabella Franco, Laura Noto, Andrea Spallanzani, Raimondo Calogero Scalia, Teresa Del Giudice, Valeria Merz, Gianmarco Motta, Alessandro Parisi, Mikol Modesti, Antonella Argentiero, Debora Basile, Gianmarco Vannini, Carlotta Ottanelli, Salvatore Corallo, Eufemia Stefania Lutrino, Daniele Rossini, Federica Morano, Luigia Stefania Stucci, Costanza Winchler, Martina Catalano, Andrea Marini, Giuseppe Brisinda, Enrico Sammarco, Martina Carullo, Giandomenico Roviello, Mirko Barone, Maria Grazia Rodriquenz, Giuseppe Tirino, Alessia Amoruso, Anna Russo, Veronica Conca, Laura Orgiano, Sveva Macrini, Giulia Nazzicone, Maria Bensi, Martina Montesano, Emanuela Dell’Aquila, Andrea Sbrana, Beatrice Borelli, Lorenzo Fornaro, Lucrezia Raimondi, Valeria Zurlo, Mattia Garutti, Elena Ongaro, Arianna Pellegrino, Andrea lanese, Laura Bernardini, Alessandra Boccaccino, Patrizia Farina, Federica Buzzacchino, Angelica Petrillo, Ada Taravella, Vittorio Studiale, Paolo Ciracì, Giovanna Lovino, Dora Di Cosmo, Sabrina Montrone, Fabiana Gregucci, Luca Dominici, Alba Fiorentino, Filippo Carannante, Giambattista Siepe, Giampaolo Montesi, Manuele Roghi, Michele Aquilano, Andrea Romei, Ilaria Bonaparte, Roberta Grassi, Emma D’Ippolito, Giulio Frosini, Giuseppina De Marco, Gennaro Giovine, Chiara Mattioli, Ilaria Morelli, Victoria Lorenzetti, Matteo Mariotti, Carolina Orsatti, Vincenzo Troncone, Lorenzo Livi, Antonio Angrisani, Marco Banini, Teresa Di Pietro, Giuseppe Carlo Iorio, Iacopo Cavallo, Cecilia Cerbai, Valerio Nardone, Francesca De Felice, Consuelo Rosa, Giulia Stocchi, Sara Lucidi, Michele Ganovelli, Damiano Dei, Chiara Cascone, Anna Peru, Luisa Caprara, Lucia Angelini, Luca Visani, Giulio Francolini, Beatrice Bettazzi, Francesco Belia, Virginia Boccardi, Simone Serafini, Vincenzo Bottino, Luca Ferrario, Giuseppe Frazzetta, Felice Pirozzi, Gennaro Martines, Francesco Antonio Ciarleglio, Daniele Indiani, Giuliano Barugola, Luca Mazza, Chiara Guarini

المصدر: Frontiers in Nutrition, Vol 10 (2023)

مصطلحات موضوعية: clinical nutrition, cancer, malnutrition, nutritional assessment, survey, Nutrition. Foods and food supply, TX341-641

الوصف: Malnutrition is a common condition in cancer patients which is usually associated with functional limitations, as well as increased morbidity and mortality. Based on the support of the young sections of Italian Association of Medical Oncology (AIOM), Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Society of Surgical Oncology (SICO) merged into the NutriOnc Research Group, we performed a multidisciplinary national survey with the aim to define the awareness of nutritional issues among healthcare professionals delivering anticancer care. The questionnaire was organized in four sections, as follows: Knowledge and practices regarding Nutritional Management of cancer patients; Timing of screening and assessment of Nutritional Status; Nutritional Treatment and prescription criteria; Immunonutrition and educational topics. The modules focused on esophagogastric, hepato-bilio-pancreatic and colorectal malignancies. Overall, 215 physicians completed the survey. As regards the management of Nutritional Status of cancer patients, many responders adopted the ERAS program (49.3%), while a consistent number of professionals did not follow a specific validated nutritional care protocol (41.8%), mainly due to lack of educational courses (14.5%) and financial support (15.3%). Nearly all the included institutions had a multidisciplinary team (92%) to finalize the treatment decision-making. Cancer patients routinely underwent nutritional screening according to 57.2% of interviewed physicians. The timing of nutritional assessment was at diagnosis (37.8%), before surgery (25.9%), after surgery (16.7%), before radiochemotherapy (13.5%) and after radiochemotherapy (7%). Most of the responders reported that nutritional status was assessed throughout the duration of cancer treatments (55.6%). An important gap between current delivery and need of nutritional assessment persists. The development of specific and defined care protocols and the adherence to these tools may be the key to improving nutritional support management in clinical practice.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnut.2023.1045022/fullTest; https://doaj.org/toc/2296-861XTest

الوصول الحر: https://doaj.org/article/befa0bfe99154a7bb366760be9ac379aTest

المؤلفون: Thomas Clarke, Pan Du, Satyendra Kumar, Shinji L. Okitsu, Mark Schuette, Qi An, Jinyang Zhang, Evgeni Tzvetkov, Mark A. Jensen, Timothy B. Niewold, Elise M. N. Ferre, Julie Nardone, Michail S. Lionakis, Jaromir Vlach, Julie DeMartino, Andrew T. Bender

المصدر: Frontiers in Immunology, Vol 14 (2023)

مصطلحات موضوعية: autoantibody, autoimmune disease (AD), autoimmune polyendocrinopathy candidiasis ecotodermal dystrophy (APECED), B cell receptor (BCR), Sjogren's syndrome, systemic lupus erythematosus (SLE), Immunologic diseases. Allergy, RC581-607

الوصف: Autoimmune diseases vary in the magnitude and diversity of autoantibody profiles, and these differences may be a consequence of different types of breaks in tolerance. Here, we compared the disparate autoimmune diseases autoimmune polyendocrinopathy–candidiasis–ecto-dermal dystrophy (APECED), systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SjS) to gain insight into the etiology of breaks in tolerance triggering autoimmunity. APECED was chosen as a prototypical monogenic disease with organ-specific pathology while SjS and SLE represent polygenic autoimmunity with focal or systemic disease. Using protein microarrays for autoantibody profiling, we found that APECED patients develop a focused but highly reactive set of shared mostly anti-cytokine antibodies, while SLE patients develop broad and less expanded autoantibody repertoires against mostly intracellular autoantigens. SjS patients had few autoantibody specificities with the highest shared reactivities observed against Ro-52 and La. RNA-seq B-cell receptor analysis revealed that APECED samples have fewer, but highly expanded, clonotypes compared with SLE samples containing a diverse, but less clonally expanded, B-cell receptor repertoire. Based on these data, we propose a model whereby the presence of autoreactive T-cells in APECED allows T-dependent B-cell responses against autoantigens, while SLE is driven by breaks in peripheral B-cell tolerance and extrafollicular B-cell activation. These results highlight differences in the autoimmunity observed in several monogenic and polygenic disorders and may be generalizable to other autoimmune diseases.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1106537/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/e823a778e94642ba916ed495ae37f622Test