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Molecular Insights in Rheumatoid Arthritis

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Dear Colleagues,

We are pleased to announce a Special Issue of International Journal of Molecular Sciences focused on "Molecular Insights in Rheumatoid Arthritis". This Issue aims to bring together the latest research on the molecular mechanisms that lead to the development and progression of rheumatoid arthritis—a chronic autoimmune disease that affects approximately 1% of the world’s population. In the last 20 years, advances in molecular-targeted drugs have led to significant advances in the treatment of rheumatoid arthritis. However, a significant proportion of RA patients do not effectively respond to current therapies, and thus new drugs are urgently required.

We invite original research articles, review articles, and communications that provide new insights into the genetic and epigenetic factors that contribute to RA susceptibility and severity, the molecular pathways that regulate inflammation and tissue destruction, the role of immune cells in the pathogenesis of RA, and the molecular mechanisms of current and emerging therapies for RA. By bringing together cutting-edge research on the molecular insights of rheumatoid arthritis, we hope to deepen our understanding of this complex disease, and contribute to the development of more effective therapies for those affected.

We look forward to your contributions to this exciting Special Issue.

Prof. Dr. Hajime Kono
Guest Editor

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17 pages, 3324 KiB

Open AccessArticle

Exploring the Link between Hydrodynamic Size and Immunoglobulins of Circulating Immune Complexes in Rheumatoid Arthritis Patients

by Tamara Djukić, Ivana Drvenica, Marijana Kovačić, Sladjan Milanović, Dragana Majerič, Mirjana Šefik-Bukilica, Maja Miletić, Branko Bugarski and Vesna Ilić

Int. J. Mol. Sci. 2024, 25(6), 3138; https://doi.org/10.3390/ijms25063138 - 08 Mar 2024

Viewed by 541

Abstract

The function of immune complexes in rheumatoid arthritis (RA) is related to their composition and size. Using dynamic light scattering (DLS), we investigated the link between the RA circulating immune complex (CIC) particles’ size and the CIC immunoglobulin level. In this study, 30 RA patients and 30 healthy individuals were included. IgA, IgG, and IgM were found in all analyzed CICs, but more IgA and IgG were found in RA than in control CICs. In both control and RA CICs, DLS detected 50 particles that differed in size and clustered around two size groups: with a 7.5–164 nm radius and with a 342–1718 nm radius. An increased level of IgA in RA CICs, compared to control ones, was associated with more than 50% of CIC particles. In RA, compared to the control, a higher number of CICs with 28.2 nm, 531 nm, 712 nm, and 1718 nm particles and a lower number of CICs with 78.8 nm particles were detected. This particle distribution pattern did not reflect the changes in the CIC immunoglobulin level. Thus, RA elevated CIC IgA was linked with all these particles (except the 1718 nm particle), the IgM increase was linked with 43.8 nm and 712 nm particles, and the IgG increase was linked with the 712 nm particle only. This study provides the very first data on the association between CIC particles’ size, CIC immunoglobulin level, and RA. It opens the possibility that the size of CICs determined by DLS can be used as a criterion in RA diagnosis or monitoring after a large-scale study confirmation. Full article

(This article belongs to the Special Issue Molecular Insights in Rheumatoid Arthritis)

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17 pages, 1265 KiB

Open AccessReview

The Role of Autophagy as a Trigger of Post-Translational Modifications of Proteins and Extracellular Vesicles in the Pathogenesis of Rheumatoid Arthritis

by Gloria Riitano, Serena Recalchi, Antonella Capozzi, Valeria Manganelli, Roberta Misasi, Tina Garofalo, Maurizio Sorice and Agostina Longo

Int. J. Mol. Sci. 2023, 24(16), 12764; https://doi.org/10.3390/ijms241612764 - 14 Aug 2023

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Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, characterized by persistent joint inflammation, leading to cartilage and bone destruction. Autoantibody production is directed to post-translational modified (PTM) proteins, i.e., citrullinated or carbamylated. Autophagy may be the common feature in several types of stress (smoking, joint injury, and infections) and may be involved in post-translational modifications (PTMs) in proteins and the generation of citrullinated and carbamylated peptides recognized by the immune system in RA patients, with a consequent breakage of tolerance. Interestingly, autophagy actively provides information to neighboring cells via a process called secretory autophagy. Secretory autophagy combines the autophagy machinery with the secretion of cellular content via extracellular vesicles (EVs). A role for exosomes in RA pathogenesis has been recently demonstrated. Exosomes are involved in intercellular communications, and upregulated proteins and RNAs may contribute to the development of inflammatory arthritis and the progression of RA. In RA, most of the exosomes are produced by leukocytes and synoviocytes, which are loaded with PTM proteins, mainly citrullinated proteins, inflammatory molecules, and enzymes that are implicated in RA pathogenesis. Microvesicles derived from cell plasma membrane may also be loaded with PTM proteins, playing a role in the immunopathogenesis of RA. An analysis of changes in EV profiles, including PTM proteins, could be a useful tool for the prevention of inflammation in RA patients and help in the discovery of personalized medicine. Full article

(This article belongs to the Special Issue Molecular Insights in Rheumatoid Arthritis)

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