Article
Rheumatology
Jaxaira Maggi, Montserrat Carrascal, Lilian Soto, Oscar Neira, Maria C. Cuellar, Octavio Aravena, Eddie A. James, Joaquin Abian, Dolores Jaraquemada, Diego Catalan, Juan C. Aguillon
Summary: This study analyzed the HLA-DR-associated peptidome of synovial tissue and dendritic cells in rheumatoid arthritis patients, aiming to identify potential T-cell epitopes. The researchers discovered six new epitopes recognized by CD4 + T cells and found a correlation between the frequency of IFN-gamma-producing CD4 + T cells specific for a certain peptide and disease activity.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Immunology
Juan He, Yu Li, Jian Chen, Qi Wu, Hongying Shan, Xiaocheng Wang, Miaomiao Zhang, Liping Nie, Qingwen Wang
Summary: Different subsets of CD8+ T cells are associated with clinical features and serological parameters in rheumatoid arthritis (RA). Naive CD8+ T cells are negatively correlated with disease activity, while CD8+ CD28-T cells and CD8+ CD27-T cells are positively correlated with disease activity. Activated CD8+ T cells and TCR gamma E+ CD8+ T cells may be involved in inflammation and lipid metabolism in RA.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Oncology
Jie Tan, Jialiang Chen
Summary: This study explored the correlation between abnormal changes in peripheral blood T lymphocyte subsets and disease progression in patients with active rheumatoid arthritis (RA). The results showed that CD8(+) T lymphocyte subsets were significantly suppressed in patients, while CD4(+) T lymphocyte subsets showed different manifestations. Additionally, CD4, CD8, and CD4/CD8 were identified as risk factors for disease progression in active RA patients.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2022)
Article
Rheumatology
Holly L. Rosenzweig, Emily E. Vance, Kofi Asare-Konadu, Kylie Koney, Ellen J. Lee, Atul A. Deodhar, Rouhin Sen, Liron Caplan, Ruth J. Napier
Summary: This study reveals a novel neutrophil-intrinsic role for Card9 in arthritogenic Th17 responses and the pathogenesis of AS. These data provide valuable utility in our future understanding of CARD9-specific mechanisms in spondyloarthritis.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Nutrition & Dietetics
Kayo Masuko
Summary: Glucose metabolism may be altered in rheumatoid arthritis and other autoimmune diseases, impacting the pathophysiology of these diseases. Research on glucose and its metabolism contributes to a better understanding of the role of carbohydrates in the occurrence and duration of these diseases.
Article
Rheumatology
Achilleas Floudas, Conor M. Smith, Orla Tynan, Nuno Neto, Vinod Krishna, Sarah M. Wade, Megan Hanlon, Clare Cunningham, Viviana Marzaioli, Mary Canavan, Jean M. Fletcher, Ronan H. Mullan, Suzanne Cole, Ling-Yang Hao, Michael G. Monaghan, Sunil Nagpal, Douglas J. Veale, Ursula Fearon
Summary: This study provides a global transcriptomic analysis of the synovial joints in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), revealing the immune-stromal cell interactions in synovial inflammation. The findings highlight the differential transcription profiles and interactions between cell subsets in RA and PsA, suggesting potential targets for targeted therapeutic intervention in these diseases.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
William Murray-Brown, Yanxia Guo, Annabelle Small, Katie Lowe, Helen Weedon, Malcolm D. Smith, Susan E. Lester, Susanna M. Proudman, Navin L. Rao, Ling-Yang Hao, Sunil Nagpal, Mihir D. Wechalekar
Summary: This study aimed to characterize PD-1-expressing Tph cells in early rheumatoid arthritis and found that these cells accumulate prior to fully established disease.
Article
Health Care Sciences & Services
Amanda J. Eakin, Tahanver Ahmed, Cathy M. McGeough, Stephen Drain, H. Denis Alexander, Gary D. Wright, Philip Gardiner, Dawn Small, Anthony J. Bjourson, David S. Gibson
Summary: This study investigates the relationship between disease activity in rheumatoid arthritis (RA) and the numbers and phenotypes of circulating regulatory T cells (Tregs) and monocytes. It also explores the potential sialic acid link between Tregs and monocytes and the effects of sialic acid on Treg activation and cytokine release.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Multidisciplinary Sciences
Yi-Shu Huang, Wen-Yi Tseng, Felix I. L. Clanchy, Louise M. Topping, Joy Ogbechi, Kay McNamee, Dany Perocheau, Nien-Yi Chiang, Peter Ericsson, Anette Sundstedt, Zhong-Tian Xue, Leif G. Salford, Hans-Olov Sjogren, Trevor W. Stone, Hsi-Hsien Lin, Shue-Fen Luo, Richard O. Williams
Summary: The study found that decitabine can promote the generation of regulatory T cells and has the potential to treat rheumatoid arthritis. It alleviates inflammation by inducing the expansion of induced regulatory T cells and selectively inducing apoptosis of Th1 and Th17 cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Rheumatology
Maximilian Kugler, Mirjam Dellinger, Felix Kartnig, Lena Mueller, Teresa Preglej, Leonhard X. Heinz, Elisabeth Simader, Lisa Goeschl, Stephan E. Puchner, Sebastian Weiss, Lisa E. Shaw, Matthias Farlik, Wolfgang Weninger, Giulio Superti-Furga, Josef S. Smolen, Guenter Steiner, Daniel Aletaha, Hans P. Kiener, Myles J. Lewis, Costantino Pitzalis, Anela Tosevska, Thomas Karonitsch, Michael Bonelli
Summary: Activated FLS play a critical role in synovial tissue remodeling and interaction with immune cells in rheumatoid arthritis (RA). Co-culture experiments demonstrated that cytokine-activated FLS enhance T cell activation, proliferation, and differentiation. Transcriptomic analysis revealed a correlation between FLS cytokine signatures and infiltrating CD4(+) T cells in RA synovial tissue. ICAM1 was identified as an important mediator in TNF-mediated FLS-T cell interaction.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Achilleas Floudas, Nuno Neto, Carl Orr, Mary Canavan, Phil Gallagher, Conor Hurson, Michael G. Monaghan, Sunil Nagpar, Ronan H. Mullan, Douglas J. Veale, Ursula Fearon
Summary: This study investigates pathogenic and protective polyfunctional T-cell responses in patients with rheumatoid arthritis (RA), individuals at risk (IAR), and healthy controls (HC) synovial tissue biopsies, identifying a novel population of pathogenic polyfunctional T-cells enriched in RA joints prior to clinical inflammation. Results show increased plasticity of Tfh cells and CD4 T-cell polyfunctionality in RA patients, with enrichment of memory Treg cell responses. The switch from potentially protective to pathogenic T-cell polyfunctionality prior to clinical inflammation highlights a potential therapeutic intervention opportunity in RA.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Medicine, General & Internal
Rui Su, Yanyan Wang, Fangyuan Hu, Baochen Li, Qiaoling Guo, Xinyu Zheng, Yue Liu, Chong Gao, Xiaofeng Li, Caihong Wang
Summary: Recent studies have suggested the involvement of Tfh and Tfr cells in the pathogenesis of rheumatoid arthritis. This study found elevated Tfh-like and PD-1(+) Tfh-like cells, decreased Treg, Tfr-like, and mTfr-like cells, and altered Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios in RA patients. The abnormal levels of Tfh-like cells and their subsets are closely related to B cells and the cytokines involved in RA pathogenesis.
FRONTIERS IN MEDICINE
(2021)
Article
Immunology
Nora Pernaa, Salla Keskitalo, Iftekhar Chowdhury, Antti Nissinen, Virpi Glumoff, Riikka Keski-Filppula, Juhani Junttila, Kari K. Eklund, Wenny Santaniemi, Sanna Siitonen, Mikko R. J. Seppanen, Paula Vahasalo, Markku Varjosalo, Pirjo Astrom, Timo Hautala
Summary: KLF2 variant may be associated with familial immune dysregulation, presenting with symptoms such as lymphopenia, autoimmunity, and malignancy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
Kevin L. Winthrop, Peter Nash, Kunihiro Yamaoka, Eduardo Mysler, Nasser Khan, Heidi S. Camp, Yanna Song, Jessica L. Suboticki, Jeffrey R. Curtis
Summary: In patients with RA, treatment with Upadacitinib (UPA) was associated with higher incidence and event rates of herpes zoster (HZ) compared to treatment with methotrexate (MTX) monotherapy or adalimumab (ADA) + MTX. The risk of HZ was also higher with the 30 mg dose of UPA compared to the 15 mg dose. Patients from Asia and those with a history of HZ may have an increased risk of HZ while receiving UPA.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Review
Immunology
Qi Jiang, Xin Wang, Enyu Huang, Qiao Wang, Chengping Wen, Guocan Yang, Liwei Lu, Dawei Cui
Summary: Inflammasome is a cellular complex involved in the innate inflammatory response, and its excessive or abnormal activation has been implicated in various diseases. In rheumatoid arthritis, inflammasome activation plays a key role in immune dysregulation and joint inflammation. This review summarizes recent research on inflammasome activation and its effector mechanisms in the pathogenesis of rheumatoid arthritis, as well as potential therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Dermatology
Jianghong Zhong, Qijing Li, Rikard Holmdahl
Summary: The genetic predisposition to psoriasis is linked to the PSORS1 locus within the major histocompatibility complex I region, with nonclassical molecules like Qa2 playing a role. Research on mice showed that a natural loss-of-function variant of Qa2 gene clusters can promote psoriasis. The study also found that a complete deficiency of Qa2 results in the expansion of key immune cells and exacerbates the development of psoriasis, while a single copy of Qa2-encoding genes provides protection against psoriasis but this can be overcome by a mutated Ncf1 gene.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Gonzalo Fernandez Lahore, Michael Forster, Martina Johannesson, Pierre Sabatier, Erik Lonnblom, Mike Aoun, Yibo He, Kutty Selva Nandakumar, Roman A. Zubarev, Rikard Holmdahl
Summary: Complex autoimmune diseases exhibit sexual dimorphism possibly controlled by an interplay between genetics and sex-related factors. Reduced CD2 expression in female mice affects autoreactive T cell responses, with hormonal regulation of CD2 also playing a role in human T cells. The study highlights the relevance of sex-genotype interactions and identifies CD2 as a predisposing factor in autoimmune diseases.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Mike Aoun, Xiaojie Cai, Bingze Xu, Gonzalo Fernandez Lahore, Michael Yi Bonner, Yibo He, Liselotte Backdahl, Rikard Holmdahl
Summary: This study reveals the additive effect of Clec4b and Ncf1 on arthritis by regulating neutrophil function. It also shows that Clec4b-specific stimulation triggers neutrophils into oxidative burst. These findings highlight the importance of Clec4b as a regulator of neutrophils and demonstrate how epistatic interactions affect the susceptibility to, and severity of, autoimmune arthritis.
Article
Rheumatology
Mikael Brink, Lotta Ljung, Monika Hansson, Johan Ronnelid, Rickard Holmdahl, Karl Skriner, Guy Serre, Lars Klareskog, Solbritt Rantapaa-Dahlqvist
Summary: This study found that the presence of certain ACPA and the number of ACPA specificities were associated with the development of PF in early RA patients. These findings contribute to a better understanding of the mechanisms and risk factors for PF development in RA patients.
Article
Biology
Cecilia Fahlquist-Hagert, Outi Sareila, Sofia Rosendahl, Rikard Holmdahl
Summary: This study investigated the effects of beta-glucan polysaccharides in arthritis and as regulators of psoriasis and PsA-like symptoms in mice. The results showed that beta-glucans down-regulated disease in mice and the protection was dependent on macrophage mannose receptor. Furthermore, beta-glucans could ameliorate PsA-like symptoms, suggesting a potential clinical treatment option.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chang He, Huqiao Luo, Ana Coelho, Meng Liu, Qijing Li, Jing Xu, Alexander Kra, Stephen Malin, Zuyi Yuan, Rikard Holmdahl
Summary: Defective production of reactive oxygen species (ROS) by NCF4 variants leads to enhanced production of autoantibodies and severe arthritis. The NCF4 mutation does not affect extracellular ROS responses, but decreases intracellular responses in B cells. NCF4 regulates terminal differentiation of B cells to plasma cells through intracellular ROS.
Article
Rheumatology
Mariele Gatto, Sara Bjursten, Charlotte A. Jonsson, Monica Leu Agelii, Caroline Jonell, Sarah McGrath, Erik Loennblom, Outi Sareila, Rikard Holmdahl, Anna Rudin, Max Levin, Inger Gjertsson
Summary: We investigated the correlation between B cell-related immunologic changes and the development of inflammatory arthritis (IA) after treatment with immune checkpoint inhibitors (ICIs). Our results showed that patients with ICI-induced IA had higher proportions of CD19+ B cells and increased levels of transitional B cells compared to patients without immune-related adverse events. Autoantibodies to joint-related proteins were also detected in ICI-IA patients. Monitoring of B cell-driven abnormalities during ICI treatment may help in early recognition of ICI-IA.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Vilma Urbonaviciute, Laura Romero-Castillo, Bingze Xu, Huqiao Luo, Nadine Schneider, Sylvia Weisse, Nhu-Nguyen Do, Ana Oliveira-Coelho, Gonzalo Fernandez Lahore, Taotao Li, Pierre Sabatier, Christian M. Beusch, Johan Viljanen, Roman A. Zubarev, Jan Kihlberg, Johan Baecklund, Harald Burkhardt, Rikard Holmdahl
Summary: The long-term goal is to find a vaccine for autoimmune diseases. It has been challenging to safely regulate the targeting of natural regulatory antigen. This study shows that the administration of exogenous MHC II protein binding a unique galactosylated COL2 peptide leads to the expansion of VISTA-positive regulatory T cells, resulting in potent suppression and protection against arthritis in mice. The tolerogenic approach described here may be a promising therapy for rheumatoid arthritis and autoimmune diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Huqiao Luo, Vilma Urbonaviciute, Amir Ata Saei, Hezheng Lyu, Massimiliano Gaetani, Akos Vegvari, Yanpeng Li, Roman A. Zubarev, Rikard Holmdahl
Summary: Mutations in NCF1 gene that cause low production of ROS are strongly linked to systemic lupus erythematosus. The deficiency of ROS in plasmacytoid dendritic cells (pDCs) exacerbates lupus development by promoting pDC accumulation in multiple organs, elevating IFN-alpha levels, and activating IFN-stimulated genes. Mechanistic studies show that ROS deficiency enhances pDC generation and migration, which further augment type I IFN responses. Restoring NOX2-derived ROS specifically in pDCs protects against lupus by suppressing these pathways.
Article
Biochemistry & Molecular Biology
Balik Dzhambazov, Tsvetelina Batsalova, Patrick Merky, Franziska Lange, Rikard Holmdahl
Summary: This study investigates the impact of different types of fibroblasts on the pathogenesis of rheumatoid arthritis (RA). The results show that only NIH/3T3 fibroblasts can activate T-cell hybridomas specific for the RA-associated autoantigen COL2, while other types of fibroblasts cannot. This activation occurs through contact-dependent intercellular interactions and the T-cell receptor (TCR) complex.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yanpeng Li, Zhilei Li, Kutty Selva Nandakumar, Rikard Holmdahl
Summary: A recent study found that a single nucleotide variant (NCF1(R90H)) on the NCF1 gene was associated with low production of reactive oxygen species (ROS) and causative for several autoimmune diseases. The study induced psoriasis in the skin and psoriatic arthritis using mannan and evaluated the effects. It was found that the NCF1(90H) variant promoted psoriasis and psoriatic arthritis by hyperactivating macrophages, expanding keratinocytes, and increasing numbers of γδT17 cells.
Article
Rheumatology
Eleftheria Pertsinidou, Saedis Saevarsdottir, Vivek Anand Manivel, Lars Klareskog, Lars Alfredsson, Linda Mathsson-Alm, Monika Hansson, Martin Cornillet, Guy Serre, Rikard Holmdahl, Karl Skriner, Per-Johan Jakobsson, Helga Westerlind, Johan Askling, Johan Roennelid
Summary: In early RA patients, ACPA is associated with a lower number of affected joints, while RF is associated with elevated systemic inflammation markers in an ACPA-dependent manner. This finding supports the in vitro models of ACPA and RF in immune complex-induced inflammation. These phenotypic associations are independent of classification criteria.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Peibin Liang, Yanpeng Li, Rui Xu, Kutty Selva Nandakumar, Roma Stawikowska, Gregg B. Fields, Rikard Holmdahl
Summary: This study characterized the chronic phase of antibody-induced arthritis in mice with Ncf1 mutation, which imitates rheumatoid arthritis. The results showed that the arthritis in these mice developed as a chronic and relapsing disease course, accompanied by bone erosions and sustained neutrophil type of inflammatory responses.
MOLECULAR BIOMEDICINE
(2022)
