Pub Date : 2024-01-24DOI: 10.1101/2024.01.23.24301671
Ilya Kister, Ryan Curtin, Amanda L Piquet, Tyler Borko, Jinglan Pei, Barbara L Banbury, Tamar E Bacon, Angie Kim, Michael Tuen, Yogambigai Velmurugu, Samantha Nyovanie, Sean Selva, Marie I Samanovic, Mark J Mulligan, Yury Patskovsky, Jessica Priest, Mark Cabatingan, Ryan C Winger, Michelle Krogsgaard, Gregg J Silverman
Pub Date : 2023-12-20DOI: 10.1101/2023.12.19.23300188
Aaron Bodansky, David JL Yu, Alysa Rallistan, Muge Kalaycioglu, Jim Boonyaratanakornkit, Damian J Green, Jordan Gauthier, Cameron J Turtle, Kelsey Zorn, Brian O'Donovan, Caleigh Mandel-Brehm, James Asaki, Hannah Kortbawi, Andrew F Kung, Elze Rackaityte, Chung-Yu Wang, Aditi Saxena, Kimberly de Dios, Gianvito Masi, Richard J Nowak, Kevin C O'Connor, Hao Li, Valentina E Diaz, Kaitlin B Casaletto, Eva Q Gontrum, Brandon Chan, Joel H Kramer, Michael R Wilson, Paul J Utz, Joshua A Hill, Shaun W Jackson, Mark S Anderson, Joseph L DeRisi
The prevalence and burden of autoimmune and autoantibody mediated disease is increasing worldwide, yet most disease etiologies remain unclear. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leverage advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology to explore the modulation, or lack thereof, of proteome-wide autoantibody profiles in both health and disease. We demonstrate that each individual, regardless of disease state, possesses a distinct set of autoreactivities constituting a unique immunological fingerprint, or autoreactome, that is remarkably stable over years. In addition to uncovering important new biology, the autoreactome can be used to better evaluate the relative effectiveness of various therapies in altering autoantibody repertoires. We find that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly alter an individuals autoreactome, while anti-CD19 and CD-20 therapies have minimal effects, strongly suggesting a rationale for BCMA or other plasma cell targeted therapies in autoantibody mediated diseases.
{"title":"Unveiling the autoreactome: Proteome-wide immunological fingerprints reveal the promise of plasma cell depleting therapy","authors":"Aaron Bodansky, David JL Yu, Alysa Rallistan, Muge Kalaycioglu, Jim Boonyaratanakornkit, Damian J Green, Jordan Gauthier, Cameron J Turtle, Kelsey Zorn, Brian O'Donovan, Caleigh Mandel-Brehm, James Asaki, Hannah Kortbawi, Andrew F Kung, Elze Rackaityte, Chung-Yu Wang, Aditi Saxena, Kimberly de Dios, Gianvito Masi, Richard J Nowak, Kevin C O'Connor, Hao Li, Valentina E Diaz, Kaitlin B Casaletto, Eva Q Gontrum, Brandon Chan, Joel H Kramer, Michael R Wilson, Paul J Utz, Joshua A Hill, Shaun W Jackson, Mark S Anderson, Joseph L DeRisi","doi":"10.1101/2023.12.19.23300188","DOIUrl":"https://doi.org/10.1101/2023.12.19.23300188","url":null,"abstract":"The prevalence and burden of autoimmune and autoantibody mediated disease is increasing worldwide, yet most disease etiologies remain unclear. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leverage advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology to explore the modulation, or lack thereof, of proteome-wide autoantibody profiles in both health and disease. We demonstrate that each individual, regardless of disease state, possesses a distinct set of autoreactivities constituting a unique immunological fingerprint, or autoreactome, that is remarkably stable over years. In addition to uncovering important new biology, the autoreactome can be used to better evaluate the relative effectiveness of various therapies in altering autoantibody repertoires. We find that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly alter an individuals autoreactome, while anti-CD19 and CD-20 therapies have minimal effects, strongly suggesting a rationale for BCMA or other plasma cell targeted therapies in autoantibody mediated diseases.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138821850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-19DOI: 10.1101/2023.12.18.23300109
Duan Ni, Alistair Senior, David Raubenheimer, Stephen Simpson, Laurence Macia, Ralph Nanan
Objectives Global age-standardized prevalence of asthma has decreased over time, in parallel with which, the gross domestic product (GDP) per capita and nutritional landscapes also changed at a global level. Both socioeconomic status and nutritional factors are critical confounder for asthma, but most studies so far neglected to interrogate their correlations and interactions comprehensively. Hence, we aim to systematically investigate the relationship between nutrient supply, a good proxy of food environment, socioeconomic status and asthma disease burden at a global level over time. Methods Asthma disease burden, macronutrient (protein, carbohydrate and fat) supply and GDP data covering more than 150 countries around the globe from 1990 to 2018 was collated. Various multi-response generalized additive mixed models (GAMMs) were used to analyze the effects of macronutrient supplies and GDP over time on asthma disease burden. Results A model considering the interactions between macronutrient supplies and GDP, with an additive effect of time was favoured. Modelling results showed that carbohydrate supply was most strongly associated with increase of asthma disease burden, while fat supply had an opposite effect, and protein supply conferred less influences. Conclusions Globally, carbohydrate supply seems to play a driving role for asthma disease burden while fat supply might be the opposite. This is supported by previous studies about the amelioration of established asthma by ketogenic diet and might be linked to the diet quality. Further in-depth studies are warranted, which will be critical for future clinical research and practice and public health intervention.
目的随着时间的推移，全球年龄标准化哮喘患病率有所下降，与此同时，全球人均国内生产总值（GDP）和营养状况也发生了变化。社会经济地位和营养因素都是哮喘的重要混杂因素，但迄今为止，大多数研究都忽略了对它们之间的相关性和相互作用进行全面探讨。因此，我们旨在系统地研究营养素供应（食物环境的良好代表）、社会经济地位和哮喘疾病负担之间的关系。方法整理了 1990 年至 2018 年全球 150 多个国家的哮喘疾病负担、宏量营养素（蛋白质、碳水化合物和脂肪）供应和 GDP 数据。采用各种多反应广义加性混合模型（GAMM）分析随时间变化的常量营养素供应和国内生产总值对哮喘疾病负担的影响。结果 一个考虑到常量营养素供应和国内生产总值之间的相互作用以及时间的叠加效应的模型受到青睐。建模结果表明，碳水化合物的供应与哮喘疾病负担的增加关系最为密切，而脂肪供应的影响则相反，蛋白质供应的影响较小。结论在全球范围内，碳水化合物供应似乎对哮喘疾病负担起着推动作用，而脂肪供应则可能相反。这一点得到了以往有关生酮饮食可改善已确诊哮喘的研究的支持，并可能与饮食质量有关。还需要进一步深入研究，这对未来的临床研究和实践以及公共卫生干预至关重要。
{"title":"Global associations of macronutrient supply and asthma disease burden","authors":"Duan Ni, Alistair Senior, David Raubenheimer, Stephen Simpson, Laurence Macia, Ralph Nanan","doi":"10.1101/2023.12.18.23300109","DOIUrl":"https://doi.org/10.1101/2023.12.18.23300109","url":null,"abstract":"<strong>Objectives</strong>\u0000Global age-standardized prevalence of asthma has decreased over time, in parallel with which, the gross domestic product (GDP) per capita and nutritional landscapes also changed at a global level. Both socioeconomic status and nutritional factors are critical confounder for asthma, but most studies so far neglected to interrogate their correlations and interactions comprehensively. Hence, we aim to systematically investigate the relationship between nutrient supply, a good proxy of food environment, socioeconomic status and asthma disease burden at a global level over time. <strong>Methods</strong>\u0000Asthma disease burden, macronutrient (protein, carbohydrate and fat) supply and GDP data covering more than 150 countries around the globe from 1990 to 2018 was collated. Various multi-response generalized additive mixed models (GAMMs) were used to analyze the effects of macronutrient supplies and GDP over time on asthma disease burden. <strong>Results</strong>\u0000A model considering the interactions between macronutrient supplies and GDP, with an additive effect of time was favoured. Modelling results showed that carbohydrate supply was most strongly associated with increase of asthma disease burden, while fat supply had an opposite effect, and protein supply conferred less influences. <strong>Conclusions</strong>\u0000Globally, carbohydrate supply seems to play a driving role for asthma disease burden while fat supply might be the opposite. This is supported by previous studies about the amelioration of established asthma by ketogenic diet and might be linked to the diet quality. Further in-depth studies are warranted, which will be critical for future clinical research and practice and public health intervention.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138743048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-07DOI: 10.1101/2023.12.05.23299462
Maisey Schuler, Nadia Siles, Cole Maguire, Dzifa Amengor, Annalee Nguyen, Rebecca Wilen, Jacob Rogers, Sam Bazzi, Blaine Caslin, Christopher DiPasquale, Melissa Abigania, Eric Olson, Janelle Creaturo, Kerin Hurley, Todd A. Triplett, Justin F. Rousseau, Stephen M. Strakowski, Dennis Wylie, Jennifer Maynard, Lauren I. R. Ehrlich, Esther Melamed
Abstract Background Understanding the kinetics and longevity of antibody responses to SARS-CoV-2 is critical to informing strategies toward reducing Coronavirus disease 2019 (COVID-19) reinfections, and improving vaccination and therapy approaches. Methods We evaluated antibody titers against SARS-CoV-2 nucleocapsid (N), spike (S), and receptor binding domain (RBD) of spike in 98 convalescent participants who experienced asymptomatic, mild, moderate or severe COVID-19 disease and in 17 non-vaccinated, non-infected controls, using four different antibody assays. Participants were sampled longitudinally at 1, 3, 6, and 12 months post-SARS-CoV-2 positive PCR test. Findings Increasing acute COVID-19 disease severity correlated with higher anti-N and anti-RBD antibody titers throughout 12 months post-infection. Anti-N and anti-RBD titers declined over time in all participants, with the exception of increased anti-RBD titers post-vaccination, and the decay rates were faster in hospitalized compared to non-hospitalized participants. <50% of participants retained anti-N titers above control levels at 12 months, with non-hospitalized participants falling below control levels sooner. Nearly all hospitalized and non-hospitalized participants maintained anti-RBD titers above controls for up to 12 months, suggesting longevity of protection against severe reinfections. Nonetheless, by 6 months, few participants retained >50% of their 1-month anti-N or anti-RBD titers. Vaccine-induced increases in anti-RBD titers were greater in non-hospitalized relative to hospitalized participants. Early convalescent antibody titers correlated with age, but no association was observed between Post-Acute Sequelae of SARS-CoV-2 infection (PASC) status or acute steroid treatment and convalescent antibody titers. Interpretation Hospitalized participants developed higher anti-SARS-CoV-2 antibody titers relative to non-hospitalized participants, a difference that persisted throughout 12 months, despite the faster decline in titers in hospitalized participants. In both groups, while anti-N titers fell below control levels for at least half of the participants, anti-RBD titers remained above control levels for almost all participants over 12 months, demonstrating generation of long-lived antibody responses known to correlate with protection from severe disease across COVID-19 severities. Overall, our findings contribute to the evolving understanding of COVID-19 antibody dynamics. Funding Austin Public Health, NIAAA, Babson Diagnostics, Dell Medical School Startup.
{"title":"SARS-CoV-2 Humoral Immune Responses in Convalescent Individuals Over 12 Months Reveal Severity-Dependent Antibody Dynamics","authors":"Maisey Schuler, Nadia Siles, Cole Maguire, Dzifa Amengor, Annalee Nguyen, Rebecca Wilen, Jacob Rogers, Sam Bazzi, Blaine Caslin, Christopher DiPasquale, Melissa Abigania, Eric Olson, Janelle Creaturo, Kerin Hurley, Todd A. Triplett, Justin F. Rousseau, Stephen M. Strakowski, Dennis Wylie, Jennifer Maynard, Lauren I. R. Ehrlich, Esther Melamed","doi":"10.1101/2023.12.05.23299462","DOIUrl":"https://doi.org/10.1101/2023.12.05.23299462","url":null,"abstract":"Abstract\u0000Background\u0000Understanding the kinetics and longevity of antibody responses to SARS-CoV-2 is critical to informing strategies toward reducing Coronavirus disease 2019 (COVID-19) reinfections, and improving vaccination and therapy approaches. Methods\u0000We evaluated antibody titers against SARS-CoV-2 nucleocapsid (N), spike (S), and receptor binding domain (RBD) of spike in 98 convalescent participants who experienced asymptomatic, mild, moderate or severe COVID-19 disease and in 17 non-vaccinated, non-infected controls, using four different antibody assays. Participants were sampled longitudinally at 1, 3, 6, and 12 months post-SARS-CoV-2 positive PCR test. Findings\u0000Increasing acute COVID-19 disease severity correlated with higher anti-N and anti-RBD antibody titers throughout 12 months post-infection. Anti-N and anti-RBD titers declined over time in all participants, with the exception of increased anti-RBD titers post-vaccination, and the decay rates were faster in hospitalized compared to non-hospitalized participants. <50% of participants retained anti-N titers above control levels at 12 months, with non-hospitalized participants falling below control levels sooner. Nearly all hospitalized and non-hospitalized participants maintained anti-RBD titers above controls for up to 12 months, suggesting longevity of protection against severe reinfections. Nonetheless, by 6 months, few participants retained >50% of their 1-month anti-N or anti-RBD titers. Vaccine-induced increases in anti-RBD titers were greater in non-hospitalized relative to hospitalized participants. Early convalescent antibody titers correlated with age, but no association was observed between Post-Acute Sequelae of SARS-CoV-2 infection (PASC) status or acute steroid treatment and convalescent antibody titers. Interpretation\u0000Hospitalized participants developed higher anti-SARS-CoV-2 antibody titers relative to non-hospitalized participants, a difference that persisted throughout 12 months, despite the faster decline in titers in hospitalized participants. In both groups, while anti-N titers fell below control levels for at least half of the participants, anti-RBD titers remained above control levels for almost all participants over 12 months, demonstrating generation of long-lived antibody responses known to correlate with protection from severe disease across COVID-19 severities. Overall, our findings contribute to the evolving understanding of COVID-19 antibody dynamics. Funding\u0000Austin Public Health, NIAAA, Babson Diagnostics, Dell Medical School Startup.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"108 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138554876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-30DOI: 10.1101/2023.11.30.23299243
David J. Gregory, Feifei Han, Peng Li, Marina Gritsenko, Jennifer Kyle, Frank E. Riley, Deborah Chavez, Vania Yotova, Renata H.M. Sindeaux, Mohamed B. F. Hawash, Fengyun Xu, Li-Yuan Hung, Douglas L. Hayden, Ron G. Tompkins, Robert E. Lanford, Lester Kobzik, Judith Hellman, Jonathan M. Jacobs, Luis B. Barreiro, Wenzhong Xiao, H. Shaw Warren
Vertebrates differ greatly in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species. After LPS stimulation, maximally different genes in resilient species included genes that detoxify LPS, diminish bacterial growth, discriminate sepsis from SIRS, and play roles in autophagy and apoptosis. The findings reveal the molecular landscape of species differences in inflammation, and may inform better selection of species for pre-clinical models.
{"title":"Multi-Omic blood analysis reveals differences in innate inflammatory sensitivity between species","authors":"David J. Gregory, Feifei Han, Peng Li, Marina Gritsenko, Jennifer Kyle, Frank E. Riley, Deborah Chavez, Vania Yotova, Renata H.M. Sindeaux, Mohamed B. F. Hawash, Fengyun Xu, Li-Yuan Hung, Douglas L. Hayden, Ron G. Tompkins, Robert E. Lanford, Lester Kobzik, Judith Hellman, Jonathan M. Jacobs, Luis B. Barreiro, Wenzhong Xiao, H. Shaw Warren","doi":"10.1101/2023.11.30.23299243","DOIUrl":"https://doi.org/10.1101/2023.11.30.23299243","url":null,"abstract":"Vertebrates differ greatly in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species. After LPS stimulation, maximally different genes in resilient species included genes that detoxify LPS, diminish bacterial growth, discriminate sepsis from SIRS, and play roles in autophagy and apoptosis. The findings reveal the molecular landscape of species differences in inflammation, and may inform better selection of species for pre-clinical models.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-30DOI: 10.1101/2023.11.29.23299171
Stephan Baumgartner, Michelle Salvisberg, Bernard Clot, Benoît Crouzy, Peter Schmid-Grendelmeier, Heinz Singer, Christoph Ort
Background Pollinosis, commonly known as seasonal allergic rhinoconjuctivitis or hay fever, is the world’s most prevalent allergic disorder, posing substantial health and economic impacts. This study explores the application of wastewater-based epidemiology (WBE) to assess the population-scale burden of pollinosis by correlating antihistamine markers in wastewater with airborne pollen data.
{"title":"Wastewater-Based Analysis of Antihistamines to Estimate Pollinosis Disease Burden at Population-Scale","authors":"Stephan Baumgartner, Michelle Salvisberg, Bernard Clot, Benoît Crouzy, Peter Schmid-Grendelmeier, Heinz Singer, Christoph Ort","doi":"10.1101/2023.11.29.23299171","DOIUrl":"https://doi.org/10.1101/2023.11.29.23299171","url":null,"abstract":"<strong>Background</strong> Pollinosis, commonly known as seasonal allergic rhinoconjuctivitis or hay fever, is the world’s most prevalent allergic disorder, posing substantial health and economic impacts. This study explores the application of wastewater-based epidemiology (WBE) to assess the population-scale burden of pollinosis by correlating antihistamine markers in wastewater with airborne pollen data.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-24DOI: 10.1101/2023.11.24.23298981
Aysa Rezabakhsh, Masoud H. Manjili, Hossein Hosseinifard, M. Reza Sadaie
Current treatments are ineffective to cure or prevent occurrences of autoimmune psoriasis and psoriatic cardiovascular disease/CVD. Psoriasis is associated with deregulated expressions of human endogenous retroviruses (ERVs) variants. ERV transcripts and proteins are detected in lesioned biopsies—without assembled viral particles—in addition to antibody and T-cell responses against ERV-K dUTPase. In persons living with HIV-1, manifestations of psoriasis are exacerbated variably. These may depend on multiple factors, differences in ERVs expressions, subtypes of HIV-1, and/or epigenetics. This article represents a quantitative risk assessment and meta-analysis approach with an attempt to assess causality. We surmise that mutated ERVs trigger aberrant proliferation and differentiation of keratinocytes, which in turn induce proinflammatory polarization. Independent risk factors and/or covariates with a range of relative risk/RR ratios appear to significantly impact the development of autoimmune psoriasis or immune intolerance, plausibly through ERVs genes activity. Given the antihypertensive drug’s potential in psoriasis development, a probable role in promising either ERVs activation or perturbations in epigenetic factors is questionable. Although the correlational nature of the data based on RR ratios prevents making robust conclusions, we reckon that the likelihood of attributable risk factors for certain antihypertensive drugs may stem from their pleiotropic effects or potentials for inducing ERV-mediated dysregulation of keratinocytes and/or endothelial cells. These findings expand our knowledge regarding ERV activations and HIV-1, antihypertensive drugs use, and incidents of psoriatic disease, and call for exploring cell-specific therapies aimed at blocking or reversing mutated ERVs gene activity toward attaining stable remissions in psoriasis and associated CVD.
目前的治疗方法无法治愈或预防自身免疫性牛皮癣和银屑病心血管疾病/CVD的发生。牛皮癣与人内源性逆转录病毒(ERVs)变体的表达失调有关。除了针对ERV- k dUTPase的抗体和t细胞反应外，在病变活检中检测到ERV转录本和蛋白质(没有组装的病毒颗粒)。在HIV-1感染者中，银屑病的表现会不同程度地恶化。这可能取决于多种因素、erv表达差异、HIV-1亚型和/或表观遗传学。这篇文章代表了一种定量风险评估和荟萃分析方法，试图评估因果关系。我们推测，突变的erv会引发角质形成细胞的异常增殖和分化，进而诱导促炎极化。独立危险因素和/或具有相对风险/RR比值范围的协变量似乎显著影响自身免疫性牛皮癣或免疫不耐受的发展，可能是通过ERVs基因活性。鉴于抗高血压药物在银屑病发展中的潜力，其在erv激活或表观遗传因素扰动中的可能作用值得怀疑。尽管基于RR比的数据的相关性使我们无法得出强有力的结论，但我们认为某些降压药物的归因风险因素可能源于它们的多效性或诱导erv介导的角化细胞和/或内皮细胞失调的潜力。这些发现扩大了我们对ERV激活和HIV-1、降压药物使用和银屑病事件的认识，并呼吁探索旨在阻断或逆转突变ERV基因活性的细胞特异性疗法，以实现银屑病和相关CVD的稳定缓解。
{"title":"Causes of Autoimmune Psoriasis and Associated Cardiovascular Disease: Roles of Human Endogenous Retroviruses and Antihypertensive Drugs—A Systematic Review and Meta-analysis","authors":"Aysa Rezabakhsh, Masoud H. Manjili, Hossein Hosseinifard, M. Reza Sadaie","doi":"10.1101/2023.11.24.23298981","DOIUrl":"https://doi.org/10.1101/2023.11.24.23298981","url":null,"abstract":"Current treatments are ineffective to cure or prevent occurrences of autoimmune psoriasis and psoriatic cardiovascular disease/CVD. Psoriasis is associated with deregulated expressions of human endogenous retroviruses (ERVs) variants. ERV transcripts and proteins are detected in lesioned biopsies—without assembled viral particles—in addition to antibody and T-cell responses against ERV-K dUTPase. In persons living with HIV-1, manifestations of psoriasis are exacerbated variably. These may depend on multiple factors, differences in ERVs expressions, subtypes of HIV-1, and/or epigenetics. This article represents a quantitative risk assessment and meta-analysis approach with an attempt to assess causality. We surmise that mutated ERVs trigger aberrant proliferation and differentiation of keratinocytes, which in turn induce proinflammatory polarization. Independent risk factors and/or covariates with a range of relative risk/RR ratios appear to significantly impact the development of autoimmune psoriasis or immune intolerance, plausibly through ERVs genes activity. Given the antihypertensive drug’s potential in psoriasis development, a probable role in promising either ERVs activation or perturbations in epigenetic factors is questionable. Although the correlational nature of the data based on RR ratios prevents making robust conclusions, we reckon that the likelihood of attributable risk factors for certain antihypertensive drugs may stem from their pleiotropic effects or potentials for inducing ERV-mediated dysregulation of keratinocytes and/or endothelial cells. These findings expand our knowledge regarding ERV activations and HIV-1, antihypertensive drugs use, and incidents of psoriatic disease, and call for exploring cell-specific therapies aimed at blocking or reversing mutated ERVs gene activity toward attaining stable remissions in psoriasis and associated CVD.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-22DOI: 10.1101/2023.11.14.23298544
Young Hwan Park, Min Ho Kim, Myeong Geun Choi, Eun Mi Chun
Importance Earlier research on COVID-19 vaccines identified a range of adverse reactions related to proinflammatory actions that can lead to an excessive immune response and sustained inflammation. However, no study has been conducted on the association between inflammatory musculoskeletal disorders and COVID-19 vaccines.
{"title":"Correlation between COVID-19 vaccination and inflammatory musculoskeletal disorders","authors":"Young Hwan Park, Min Ho Kim, Myeong Geun Choi, Eun Mi Chun","doi":"10.1101/2023.11.14.23298544","DOIUrl":"https://doi.org/10.1101/2023.11.14.23298544","url":null,"abstract":"<strong>Importance</strong> Earlier research on COVID-19 vaccines identified a range of adverse reactions related to proinflammatory actions that can lead to an excessive immune response and sustained inflammation. However, no study has been conducted on the association between inflammatory musculoskeletal disorders and COVID-19 vaccines.","PeriodicalId":501527,"journal":{"name":"medRxiv - Allergy and Immunology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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