Emily C Somers, Jaclyn M Goodrich, Lu Wang, Sioban D Harlow, Wendy Marder, Afton L Hassett, Suzanna M Zick, W Joseph McCune, Caroline Gordon, Kamil E Barbour, Charles G Helmick, Faith M Strickland
BACKGROUND: Environmental factors can influence epigenetic regulation, including DNA methylation, potentially contributing to systemic lupus erythematosus (SLE) development and progression. We compared methylation of the B cell costimulatory CD70 gene, in persons with lupus and controls, and characterized associations with age. RESULTS: In 297 adults with SLE and 92 controls from the Michigan Lupus Epidemiology and Surveillance (MILES) Cohort, average CD70 methylation of CD4+ T cell DNA across 10 CpG sites based on pyrosequencing of the promoter region was higher for persons with SLE compared to controls, accounting for covariates [β = 2...
December 7, 2023: Journal of Autoimmunity
Nataliya Slater, Anuradha Sooda, Emily McLeish, Kelly Beer, Anna Brusch, Rakesh Shakya, Christine Bundell, Ian James, Abha Chopra, Frank L Mastaglia, Merrilee Needham, Jerome D Coudert
OBJECTIVES: Inclusion body myositis (IBM) is a progressive inflammatory-degenerative muscle disease of older individuals, with some patients producing anti-cytosolic 5'-nucleotidase 1A (NT5C1A, aka cN1A) antibodies. Human Leukocyte Antigens (HLA) is the highest genetic risk factor for developing IBM. In this study, we aimed to further define the contribution of HLA alleles to IBM and the production of anti-cN1A antibodies. METHODS: We HLA haplotyped a Western Australian cohort of 113 Caucasian IBM patients and 112 ethnically matched controls using Illumina next-generation sequencing...
December 2, 2023: Journal of Autoimmunity
Hélène Greigert, André Ramon, Coraline Genet, Claudie Cladière, Claire Gerard, Marion Cuidad, Marc Corbera-Bellalta, Roser Alba-Rovira, Louis Arnould, Catherine Creuzot-Garcher, Laurent Martin, Georges Tarris, Thibault Ghesquière, Sethi Ouandji, Sylvain Audia, Maria C Cid, Bernard Bonnotte, Maxime Samson
Vascular smooth muscle cells (VSMCs) have been shown to play a role in the pathogenesis of giant cell arteritis (GCA) through their capacity to produce chemokines recruiting T cells and monocytes in the arterial wall and their ability to migrate and proliferate in the neointima where they acquire a myofibroblast (MF) phenotype, leading to vascular stenosis. This study aimed to investigate if MFs could also impact T-cell polarization. Confocal microscopy was used to analyze fresh fragments of temporal artery biopsies (TABs)...
November 30, 2023: Journal of Autoimmunity
Keisuke Yasuda, Shieri Shimodan, Natsumi Maehara, Aika Hirota, Ruka Iijima, Akemi Nishijima, Haruka Mori, Ran Toyama, Atsumi Ito, Yuri Yoshikawa, Satoko Arai, Toru Miyazaki
The hallmark of autoimmune arthritis is the preceding autoantibody production and the following synovial inflammation with hyperplasia and tissue destruction of the joints. The joint inflammation is mediated not only by effector lymphocytes and auto-antibodies but also chronic activation of innate immunity, particularly promoted by the danger-associated molecular patterns (DAMPs). Here we show that apoptosis inhibitor of macrophage (AIM, also called CD5L) protein regulates arthritis by promoting removal of lesional DAMPs both physiologically and therapeutically...
November 24, 2023: Journal of Autoimmunity
Xuan Zhang, Jun Xia, Ying Jiang, David S Pisetsky, Josef S Smolen, Rong Mu, Shengming Dai, Michael E Weinblatt, Tore K Kvien, Juan Li, Thomas Dörner, Yu Zhang, Liwei Lu, Chengde Yang, Pingting Yang, Yuan Zhang, Chenchen Xu, Zhan Zhao, Peter E Lipsky
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the joints and produces pain, swelling, and stiffness. It has a lifetime prevalence of up to 1% worldwide. An extract of Tripterygium wilfordii Hook F (TwHF), a member of the Celastraceae herbal family widely available in south China, has been used for treatment of RA since 1960s. METHODS: The current consensus practice guidance (CPG) aims to offer guidance on the application of TwHF in the clinical management of active RA...
November 13, 2023: Journal of Autoimmunity
Johanne Liberatore, Yann Nguyen, Jérôme Hadjadj, Pascal Cohen, Luc Mouthon, Xavier Puéchal, Loïc Guillevin, Benjamin Terrier
OBJECTIVES: B-cell depletion induced by rituximab (RTX) in ANCA-associated vasculitis (AAV) is a risk factor for hypogammaglobulinemia. Aggregating data on gammaglobulin levels kinetics during RTX and its association with the risk of relapse and severe infection is of interest. METHODS: Gammaglobulin levels were collected before induction therapy and during RTX maintenance therapy. We used different definitions of gammaglobulin decline: 1/gammaglobulin levels <6 g/L after induction; 2/>25 % decline in gammaglobulin levels between induction and maintenance, and 3/both...
November 11, 2023: Journal of Autoimmunity
Maya F Amjadi, Maxwell H Parker, Ryan R Adyniec, Zihao Zheng, Alex M Robbins, S Janna Bashar, Michael F Denny, Sara S McCoy, Irene M Ong, Miriam A Shelef
Rheumatoid factors (RFs), polyreactive antibodies canonically known to bind two conformational epitopes of IgG Fc, are a hallmark of rheumatoid arthritis but also can arise in other inflammatory conditions and infections. Also, infections may contribute to the development of rheumatoid arthritis and other autoimmune diseases. Recently, RFs only in rheumatoid arthritis were found to bind novel linear IgG epitopes as well as thousands of other rheumatoid arthritis autoantigens. Specific epitopes recognized by infection-induced polyreactive RFs remain undefined but could provide insights into loss of immune tolerance...
November 11, 2023: Journal of Autoimmunity
Elio G Carmona, José Luis Callejas-Rubio, Enrique Raya, Raquel Ríos-Fernández, Gonzalo Villanueva-Martín, María C Cid, José Hernández-Rodríguez, Esteban Ballestar, Bernd Timmermann, Norberto Ortego-Centeno, Javier Martín, Ana Márquez
Giant cell arteritis (GCA) is a systemic vasculitis mediated by an aberrant immunological response against the blood vessel wall. Although the pathogenic mechanisms that drive GCA have not yet been elucidated, there is strong evidence that CD4+ T cells are key drivers of the inflammatory process occurring in this vasculitis. The aim of this study was to further delineate the role of CD4+ T cells in GCA by applying single-cell RNA sequencing and T cell receptor (TCR) repertoire profiling to 114.799 circulating CD4+ T cells from eight GCA patients in two different clinical states, active and in remission, and eight healthy controls...
November 10, 2023: Journal of Autoimmunity
Shane Kelly, Katherine Jl Jackson, Timothy J Peters, Dan Suan, Christopher C Goodnow
BACKGROUND: PR3 autoantibodies are essential to the diagnosis and monitoring of granulomatosus with polyangiitis, but to date no PR3 autoantibody sequences have been published. OBJECTIVES: To identify and characterise PR3-specific B cells from the peripheral blood of patients with PR3 autoantibodies. METHODS: Peripheral blood mononuclear cells from seven patients with PR3 autoantibodies were stained with PR3. B cells that bound PR3 underwent single cell sorting, transcriptome sequencing, and their immunoglobulin sequences expressed as antibodies and tested for PR3-specificity by ELISA...
November 10, 2023: Journal of Autoimmunity
Joshua A Reynolds, Yaxi Li, Leal Herlitz, Chandra Mohan, Chaim Putterman
OBJECTIVES: The difficulty of monitoring organ-specific pathology in systemic lupus erythematosus (SLE) often complicates disease prognostication and treatment. Improved non-invasive biomarkers of active organ pathology, particularly lupus nephritis, would improve patient care. We sought to validate and apply a novel strategy to generate the first comprehensive serum proteome of a lupus mouse model and identify mechanism-linked lupus biomarker candidates for subsequent clinical investigation...
November 7, 2023: Journal of Autoimmunity
Chuqiao Xu, Tianyu Zhang, Hailun Wang, Lin Zhu, Yue Ruan, Zixuan Huang, Jingying Wang, Haiqin Zhu, Chuanxin Huang, Meng Pan
Pemphigus, an autoimmune bullous disease affecting the skin and mucosal membranes, is primarily driven by anti-desmoglein (Dsg) autoantibodies. However, the underlying immune mechanisms of this disease remain largely elusive. Here, we compile an unbiased atlas of immune cells in pemphigus cutaneous lesions at single-cell resolution. We reveal clonally expanded antibody-secreting cells (ASCs) that exhibit variable hypermutation and accumulation of IgG4 class-switching in their immunoglobulin genes. Importantly, pathogenic Dsg-specific ASCs are localized within pemphigus lesions and can evolve from both Dsg-autoreactive and non-binding precursors...
November 6, 2023: Journal of Autoimmunity
Christopher Nelke, Thomas Müntefering, Derya Cengiz, Lukas Theissen, Vera Dobelmann, Christina B Schroeter, Helena Block, Corinna Preuße, Alexander P E Michels, Stefanie Lichtenberg, Marc Pawlitzki, Steffen Pfeuffer, Niklas Huntemann, Alexander Zarbock, Thorben Briese, Christoph Kittl, Carsten Dittmayer, Thomas Budde, Ingrid E Lundberg, Werner Stenzel, Sven G Meuth, Tobias Ruck
K2P 2.1 (TREK1), a two-pore domain potassium channel, has emerged as regulator of leukocyte transmigration into the central nervous system. In the context of skeletal muscle, immune cell infiltration constitutes the pathogenic hallmark of idiopathic inflammatory myopathies (IIMs). However, the underlying mechanisms remain to be elucidated. In this study, we investigated the role of K2P 2.1 in the autoimmune response of IIMs. We detected K2P 2.1 expression in primary skeletal muscle and endothelial cells of murine and human origin...
November 5, 2023: Journal of Autoimmunity
Hirokazu Sasaki, Natsuka Umezawa, Takuji Itakura, Hideyuki Iwai, Shinsuke Yasuda
Programmed-cell-death 1 (PD-1) expression is associated not only with T-cell activation but with exhaustion. Specifically, PD-1+ T cells present an exhausted phenotype in conditions of chronic antigen exposure, such as tumor microenvironments and chronic viral infection. However, the immune status regarding exhaustion of PD-1+ CD8+ T cells in chronic autoimmune diseases including idiopathic inflammatory myopathies (IIMs) remains unclear. We aimed to clarify the role of PD-1+ CD8+ T cells and PD-1 ligand (PD-L1) in IIMs...
November 4, 2023: Journal of Autoimmunity
Ana Merino-Vico, Jan Piet van Hamburg, Paul Tuijnenburg, Giulia Frazzei, Aram Al-Soudi, Carlo G Bonasia, Boy Helder, Abraham Rutgers, Wayel H Abdulahad, Coen A Stegeman, Jan-Stephan Sanders, Laura Bergamaschi, Paul A Lyons, Theo Bijma, Laura van Keep, Kirsten Wesenhagen, Aldo Jongejan, Henric Olsson, Niek de Vries, Taco W Kuijpers, Peter Heeringa, Sander W Tas
B lineage cells are critically involved in ANCA-associated vasculitis (AAV), evidenced by alterations in circulating B cell subsets and beneficial clinical effects of rituximab (anti-CD20) therapy. This treatment renders a long-term, peripheral B cell depletion, but allows for the survival of long-lived plasma cells. Therefore, there is an unmet need for more reversible and full B lineage cell targeting approaches. To find potential novel therapeutic targets, RNA sequencing of CD27+ memory B cells of patients with active AAV was performed, revealing an upregulated NF-κB-associated gene signature...
November 4, 2023: Journal of Autoimmunity
Jin Sun Kim, Rohit Gupta
Sarcoidosis is a systemic inflammatory disease of unknown etiology and variable clinical course. Pulmonary sarcoidosis is the most common presentation and accounts for most morbidity and mortality related to sarcoidosis. While sarcoidosis generally has good outcomes, few patients experience chronic disease. A minority of patients progress to a specific phenotype of sarcoidosis referred to advanced pulmonary sarcoidosis (APS) which includes advanced fibrosis, pulmonary hypertension and respiratory failure, leading to high morbidity and mortality...
November 1, 2023: Journal of Autoimmunity
Shu-Yi Liao, Tasha Fingerlin, Lisa Maier
Sarcoidosis is a complex systemic disease with clinical heterogeneity based on varying phenotypes and natural history. The detailed etiology of sarcoidosis remains unknown, but genetic predisposition as well as environmental exposures play a significant role in disease pathogenesis. We performed a comprehensive review of germline genetic (DNA) and transcriptomic (RNA) studies of sarcoidosis, including both previous studies and more recent findings. In this review, we provide an assessment of the following: genetic variants in sarcoidosis susceptibility and phenotypes, ancestry- and sex-specific genetic variants in sarcoidosis, shared genetic architecture between sarcoidosis and other diseases, and gene-environment interactions in sarcoidosis...
October 19, 2023: Journal of Autoimmunity
John A Belperio, Michael C Fishbein, Fereidoun Abtin, Jessica Channick, Shailesh A Balasubramanian, Joseph P Lynch Iii
Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph nodes. Worldwide it is estimated to affect 2-160/100,000 people and has a mortality rate over 5 years of approximately 7%. For sarcoidosis patients, the cause of death is due to sarcoid in 60% of the cases, of which up to 80% are from advanced cardiopulmonary failure (pulmonary hypertension and respiratory microbial infections) in all races except in Japan were greater than 70% of the sarcoidosis deaths are due to cardiac sarcoidosis...
October 19, 2023: Journal of Autoimmunity
Jelle R Miedema, Lieke J de Jong, Denise van Uden, Ingrid M Bergen, Mirjam Kool, Caroline E Broos, Vivienne Kahlmann, Marlies S Wijsenbeek, Rudi W Hendriks, Odilia B J Corneth
RATIONALE: Disease course in sarcoidosis is highly variable. Bronchoalveolar lavage fluid and mediastinal lymph nodes show accumulation of activated T cells with a T-helper (Th)17.1 signature, which correlates with non-resolving sarcoidosis. We hypothesize that the peripheral blood (PB) T cell phenotype may correlate with outcome. OBJECTIVES: To compare frequencies, phenotypes and function of circulating T cell populations in sarcoidosis patients with healthy controls (HCs) and correlate these parameters with outcome...
October 18, 2023: Journal of Autoimmunity
Takashi Kei Kishimoto, Max Fournier, Alicia Michaud, Gina Rizzo, Christopher Roy, Teresa Capela, Natasha Nukolova, Ning Li, Liam Doyle, Fen-Ni Fu, Derek VanDyke, Peter G Traber, Jamie B Spangler, Sheldon S Leung, Petr O Ilyinskii
Interleukin-2 (IL-2) therapies targeting the high affinity IL-2 receptor expressed on regulatory T cells (Tregs) have shown promising therapeutic benefit in autoimmune diseases through nonselective expansion of pre-existing Treg populations, but are potentially limited by the inability to induce antigen-specific Tregs, as well as by dose-limiting activation of effector immune cells in settings of inflammation. We recently developed biodegradable nanoparticles encapsulating rapamycin, called ImmTOR, which induce selective immune tolerance to co-administered antigens but do not increase total Treg numbers...
October 14, 2023: Journal of Autoimmunity
Christina Kazzi, Valeriya Kuznetsova, Pakeeran Siriratnam, Sarah Griffith, Shu Wong, Constantine S Tam, Rubina Alpitsis, Andrew Spencer, Terence J O'Brien, Charles B Malpas, Mastura Monif
BACKGROUND: This systematic review aimed to characterise the cognitive outcomes of patients who received chimeric antigen receptor T-cell therapy. METHODS: A systematic search of the literature was performed using PubMed, PsycINFO, SCOPUS, EMBASE, Medline, and CINAHL (February 2023). Risk of bias was assessed using the JBI Checklist for Case Reports and the Risk of Bias Assessment Tool for Non-randomised Studies. RESULTS: Twenty-two studies met inclusion criteria with a total of 1104 participants...
October 12, 2023: Journal of Autoimmunity
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