Special Issue "Rheumatoid Arthritis: Dissecting Molecular and Cellular Mechanisms towards Precision Medicine"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (1 June 2021).

Special Issue Editors

Dr. Richard O. Williams
E-Mail Website
Guest Editor
Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
Interests: rheumatoid arthritis; immunotherapy; new targets; regulatory T cells
Prof. Dr. João Eurico Fonseca
E-Mail Website
Guest Editor
1. Rheumatology Research Unit, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
2. Rheumatology Department, Centro Hospitalar Universitário Lisboa Norte, EPE, Hospital de Santa Maria, Lisbon, Portugal
Interests: early arthritis; rheumatoid arthritis; biomarkers; prognosis; response to treatment; precision medicine; new targets
Special Issues, Collections and Topics in MDPI journals
Dr. Stefano Alivernini
E-Mail Website
Guest Editor
Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
Interests: synovial tissue; rheumatoid arthritis; biomarkers; single-cell phenotyping; disease remission; precision medicine; prognostic algorithms
Dr. Monica Guma
E-Mail Website
Guest Editor
Veteran’s Affairs San Diego Health System, University of California, San Diego, CA, USA
Interests: rheumatoid arthritis; osteoarthritis; synovitis; immunometabolism; metabolomics; biomarkers

Special Issue Information

Dear Colleagues,

Over the last decades, increasing insights in the molecular and cellular immunopathology of rheumatoid arthritis (RA) have been translated into highly effective targeted therapies that have profoundly altered daily medical practice. However, the response to current therapies is highly heterogenous, and it has become clear that we should start to consider RA as an overarching phenotype, resulting from a network of complex and sometimes redundant pathways. The challenge now is to integrate this knowledge into our diagnostic, prognostic, and therapeutic approaches, aiming at taking a step forward towards precision medicine, as other fields of medicine have successfully achieved.

This Special Issue seeks to create a multidisciplinary forum for the interaction of basic scientists, physician scientists, and clinicians, exploring the intrinsic biological processes involved in recognition, signaling, effector function, and the regulation of innate and adaptive immunity and how a knowledge of these processes can help us to prevent RA, make appropriate first-line treatment choices, and improve treatment outcomes in RA.

We are looking forward to your contributions to this Special Issue.

Dr. Richard O. Williams
Dr. João Eurico Fonseca
Dr. Stefano Alivernini
Dr. Monica Guma
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • rheumatoid arthritis
  • immunotherapy
  • new targets
  • early arthritis
  • biomarkers
  • prognosis
  • response to treatment
  • precision medicine
  • synovial tissue
  • single-cell phenotyping
  • disease remission
  • prognostic algorithms
  • osteoarthritis
  • synovitis
  • immunometabolism
  • metabolomics

Published Papers (3 papers)

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Research

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Article
Peripheral Blood from Rheumatoid Arthritis Patients Shows Decreased Treg CD25 Expression and Reduced Frequency of Effector Treg Subpopulation
Cells 2021, 10(4), 801; https://doi.org/10.3390/cells10040801 - 03 Apr 2021
Cited by 2 | Viewed by 698
Abstract
Rheumatoid arthritis (RA) is a common autoimmune disease characterized by immune cell infiltration of the synovium, leading to the loss of cartilage, bone, and joint function. Although regulatory T (Treg) cells are thought to modulate the initiation and progression of RA, [...] Read more.
Rheumatoid arthritis (RA) is a common autoimmune disease characterized by immune cell infiltration of the synovium, leading to the loss of cartilage, bone, and joint function. Although regulatory T (Treg) cells are thought to modulate the initiation and progression of RA, a consensus has yet to be reached regarding the function and composition of Treg cells in RA patients. To address these discrepancies, we analyzed not only the total Treg frequency but also that of Treg subpopulations in the peripheral blood of RA patients and healthy controls by flow cytometry. We found that the total Treg population was not significantly different between RA and control subjects. However, the effector Treg cell subgroup, defined as CD45RACD25hi, showed markedly decreased frequency in RA patients. In addition, the total Treg population from RA patients showed a significant decline in the expression of CD25. Both the naïve and effector Treg subgroups also showed marked reduction of CD25 expression in RA patients compared to controls. These data suggest that the decreased frequency of effector Treg cells and overall reduction of CD25 expression in Treg cells in the peripheral blood may be evidence of altered Treg homeostasis associated with RA pathogenesis. Full article
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Article
ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis
Cells 2021, 10(3), 647; https://doi.org/10.3390/cells10030647 - 14 Mar 2021
Cited by 3 | Viewed by 1020
Abstract
Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for the diagnosis of RA, however 20–30% of patients are ACPA negative. ACPA status is a delineator of RA disease [...] Read more.
Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for the diagnosis of RA, however 20–30% of patients are ACPA negative. ACPA status is a delineator of RA disease endotypes with similar clinical manifestation but potentially different pathophysiology. Profiling of key peripheral blood and synovial tissue immune populations including B cells, T follicular helper (Tfh) cells and CD4 T cell proinflammatory cytokine responses could elucidate the underlying immunological mechanisms involved and inform a treat to target approach for both ACPA-positive and ACPA-negative RA. Detailed high dimensionality flow cytometric analysis with supervised and unsupervised algorithm analysis revealed unique RA patient peripheral blood B cell and Tfh cell profiles. Synovial tissue single cell analysis of B cell subpopulation distribution was similar between ACPA− and ACPA+ RA patients, highlighting a key role for specific B cell subsets in both disease endotypes. Interestingly, synovial tissue single cell analysis of CD4 T cell proinflammatory cytokine production was markedly different between ACPA− and APCA+ RA patients. RNAseq analysis of RA patient synovial tissue highlighted disease endotype specific gene signatures. ACPA status associates with unique immune profile signatures that reinforce the need for a treat to target approach for both endotypes of RA. Full article
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Review

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Review
Biologic Drugs for Rheumatoid Arthritis in the Context of Biosimilars, Genetics, Epigenetics and COVID-19 Treatment
Cells 2021, 10(2), 323; https://doi.org/10.3390/cells10020323 - 04 Feb 2021
Cited by 3 | Viewed by 1395
Abstract
Rheumatoid arthritis (RA) affects around 1.2% of the adult population. RA is one of the main reasons for work disability and premature retirement, thus substantially increasing social and economic burden. Biological disease-modifying antirheumatic drugs (bDMARDs) were shown to be an effective therapy especially [...] Read more.
Rheumatoid arthritis (RA) affects around 1.2% of the adult population. RA is one of the main reasons for work disability and premature retirement, thus substantially increasing social and economic burden. Biological disease-modifying antirheumatic drugs (bDMARDs) were shown to be an effective therapy especially in those rheumatoid arthritis (RA) patients, who did not adequately respond to conventional synthetic DMARD therapy. However, despite the proven efficacy, the high cost of the therapy resulted in limitation of the widespread use and unequal access to the care. The introduction of biosimilars, which are much cheaper relative to original drugs, may facilitate the achievement of the therapy by a much broader spectrum of patients. In this review we present the properties of original biologic agents based on cytokine-targeted (blockers of TNF, IL-6, IL-1, GM-CSF) and cell-targeted therapies (aimed to inhibit T cells and B cells properties) as well as biosimilars used in rheumatology. We also analyze the latest update of bDMARDs’ possible influence on DNA methylation, miRNA expression and histone modification in RA patients, what might be the important factors toward precise and personalized RA treatment. In addition, during the COVID-19 outbreak, we discuss the usage of biologicals in context of effective and safe COVID-19 treatment. Therefore, early diagnosing along with therapeutic intervention based on personalized drugs targeting disease-specific genes is still needed to relieve symptoms and to improve the quality of life of RA patients. Full article
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