Research

20 pages, 4494 KiB

Open AccessArticle

Comprehensive Profiling of Early Neoplastic Gastric Microenvironment Modifications and Biodynamics in Impaired BMP-Signaling FoxL1⁺-Telocytes

by Alain B. Alfonso, Véronique Pomerleau, Vilcy Reyes Nicolás, Jennifer Raisch, Carla-Marie Jurkovic, François-Michel Boisvert and Nathalie Perreault

Biomedicines 2023, 11(1), 19; https://doi.org/10.3390/biomedicines11010019 - 22 Dec 2022

Viewed by 1364

Abstract

FoxL1⁺telocytes (TC^FoxL1+) are novel gastrointestinal subepithelial cells that form a communication axis between the mesenchyme and epithelium. TC^FoxL1+ are strategically positioned to be key contributors to the microenvironment through production and secretion of growth factors and extracellular matrix [...] Read more.

FoxL1⁺telocytes (TC^FoxL1+) are novel gastrointestinal subepithelial cells that form a communication axis between the mesenchyme and epithelium. TC^FoxL1+ are strategically positioned to be key contributors to the microenvironment through production and secretion of growth factors and extracellular matrix (ECM) proteins. In recent years, the alteration of the bone morphogenetic protein (BMP) signaling in TC^FoxL1+ was demonstrated to trigger a toxic microenvironment with ECM remodeling that leads to the development of pre-neoplastic gastric lesions. However, a comprehensive analysis of variations in the ECM composition and its associated proteins in gastric neoplasia linked to TC^FoxL1+ dysregulation has never been performed. This study provides a better understanding of how TC^FoxL1+ defective BMP signaling participates in the gastric pre-neoplastic microenvironment. Using a proteomic approach, we determined the changes in the complete matrisome of BmpR1a^△FoxL1+ and control mice, both in total antrum as well as in isolated mesenchyme-enriched antrum fractions. Comparative proteomic analysis revealed that the deconstruction of the gastric antrum led to a more comprehensive analysis of the ECM fraction of gastric tissues microenvironment. These results show that TC^FoxL1+ are key members of the mesenchymal cell population and actively participate in the establishment of the matrisomic fraction of the microenvironment, thus influencing epithelial cell behavior. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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23 pages, 3614 KiB

Open AccessArticle

Aberrant Expression and Prognostic Potential of IL-37 in Human Lung Adenocarcinoma

by Panayiota Christodoulou, Theodora-Christina Kyriakou, Panagiotis Boutsikos, Maria Andreou, Yuan Ji, Damo Xu, Panagiotis Papageorgis and Maria-Ioanna Christodoulou

Biomedicines 2022, 10(12), 3037; https://doi.org/10.3390/biomedicines10123037 - 24 Nov 2022

Cited by 3 | Viewed by 1866

Abstract

Interleukin-37 (IL-37) is a relatively new IL-1 family cytokine that, due to its immunoregulatory properties, has lately gained increasing attention in basic and translational biomedical research. Emerging evidence supports the implication of this protein in any human disorder in which immune homeostasis is [...] Read more.

Interleukin-37 (IL-37) is a relatively new IL-1 family cytokine that, due to its immunoregulatory properties, has lately gained increasing attention in basic and translational biomedical research. Emerging evidence supports the implication of this protein in any human disorder in which immune homeostasis is compromised, including cancer. The aim of this study was to explore the prognostic and/or diagnostic potential of IL-37 and its receptor SIGIRR (single immunoglobulin IL-1-related receptor) in human tumors. We utilized a series of bioinformatics tools and -omics datasets to unravel possible associations of IL-37 and SIGIRR expression levels and genetic aberrations with tumor development, histopathological parameters, distribution of tumor-infiltrating immune cells, and survival rates of patients. Our data revealed that amongst the 17 human malignancies investigated, IL-37 exhibits higher expression levels in tumors of lung adenocarcinoma (LUAD). Moreover, the expression profiles of IL-37 and SIGIRR are associated with LUAD development and tumor stage, whereas their high mRNA levels are favorable prognostic factors for the overall survival of patients. What is more, IL-37 correlates positively with a LUAD-associated transcriptomic signature, and its nucleotide changes and expression levels are linked with distinct infiltration patterns of certain cell subsets known to control LUAD anti-tumor immune responses. Our data indicate the potential value of IL-37 and its receptor SIGIRR to serve as biomarkers and/or immune-checkpoint therapeutic targets for LUAD patients. Further, the data highlight the urgent need for further exploration of this cytokine and the underlying pathogenetic mechanisms to fully elucidate its implication in LUAD development and progression. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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15 pages, 751 KiB

Open AccessArticle

Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes

by Nabarun Chakraborty, Seshamalini Srinivasan, Ruoting Yang, Stacy-Ann Miller, Aarti Gautam, Leanne J. Detwiler, Bonnie C. Carney, Abdulnaser Alkhalil, Lauren T. Moffatt, Marti Jett, Jeffrey W. Shupp and Rasha Hammamieh

Biomedicines 2022, 10(6), 1402; https://doi.org/10.3390/biomedicines10061402 - 14 Jun 2022

Cited by 1 | Viewed by 1541

Abstract

Staphylococcus aureus, a gram-positive bacterium, causes toxic shock through the production of superantigenic toxins (sAgs) known as Staphylococcal enterotoxins (SE), serotypes A-J (SEA, SEB, etc.), and toxic shock syndrome toxin-1 (TSST-1). The chronology of host transcriptomic events that characterizes the response to [...] Read more.

Staphylococcus aureus, a gram-positive bacterium, causes toxic shock through the production of superantigenic toxins (sAgs) known as Staphylococcal enterotoxins (SE), serotypes A-J (SEA, SEB, etc.), and toxic shock syndrome toxin-1 (TSST-1). The chronology of host transcriptomic events that characterizes the response to the pathogenesis of superantigenic toxicity remains uncertain. The focus of this study was to elucidate time-resolved host responses to three toxins of the superantigenic family, namely SEA, SEB, and TSST-1. Due to the evolving critical role of melanocytes in the host’s immune response against environmental harmful elements, we investigated herein the transcriptomic responses of melanocytes after treatment with 200 ng/mL of SEA, SEB, or TSST-1 for 0.5, 2, 6, 12, 24, or 48 h. Functional analysis indicated that each of these three toxins induced a specific transcriptional pattern. In particular, the time-resolved transcriptional modulations due to SEB exposure were very distinct from those induced by SEA and TSST-1. The three superantigens share some similarities in the mechanisms underlying apoptosis, innate immunity, and other biological processes. Superantigen-specific signatures were determined for the functional dynamics related to necrosis, cytokine production, and acute-phase response. These differentially regulated networks can be targeted for therapeutic intervention and marked as the distinguishing factors for the three sAgs. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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12 pages, 1076 KiB

Open AccessArticle

Gelsolin as a Potential Biomarker for Endoscopic Activity and Mucosal Healing in Ulcerative Colitis

by Keiko Maeda, Masanao Nakamura, Takeshi Yamamura, Tsunaki Sawada, Eri Ishikawa, Akina Oishi, Shuji Ikegami, Naomi Kakushima, Kazuhiro Furukawa, Tadashi Iida, Yasuyuki Mizutani, Takuya Ishikawa, Eizaburo Ohno, Takashi Honda, Masatoshi Ishigami and Hiroki Kawashima

Biomedicines 2022, 10(4), 872; https://doi.org/10.3390/biomedicines10040872 - 09 Apr 2022

Cited by 4 | Viewed by 1802

Abstract

The therapeutic goal in ulcerative colitis is mucosal healing, which requires improved non-invasive biomarkers to evaluate disease activity. Gelsolin is associated with several autoimmune diseases, and here, we aimed to analyze its usefulness as a serological biomarker for clinical and endoscopic activities in [...] Read more.

The therapeutic goal in ulcerative colitis is mucosal healing, which requires improved non-invasive biomarkers to evaluate disease activity. Gelsolin is associated with several autoimmune diseases, and here, we aimed to analyze its usefulness as a serological biomarker for clinical and endoscopic activities in ulcerative colitis. Patients with ulcerative colitis (n = 138) who had undergone blood tests and colonoscopy were included. Serum gelsolin was measured using enzyme-linked immunosorbent assay, and correlation between the gelsolin level and clinical and endoscopic activities was examined. The serum gelsolin level in patients with ulcerative colitis was significantly lower than that in healthy subjects, and it decreased in proportion to increasing Mayo score and Mayo endoscopic subscore. The area under the curve for correlation between clinical and endoscopic remission and serum gelsolin level was higher than that for C-reactive protein. Furthermore, in C-reactive protein-negative patients, the serum gelsolin level was lower in the active phase than in remission. Our findings indicate that the serum gelsolin level correlates with clinical and endoscopic activities in ulcerative colitis, has a higher sensitivity and specificity than C-reactive protein, and can detect mucosal healing, suggesting that gelsolin can be used as a biomarker for ulcerative colitis. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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15 pages, 2549 KiB

Open AccessArticle

Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthritis

by Jeneen Panezai, Ambereen Ghaffar, Mohammad Altamash, Mikael Åberg, Thomas E. Van Dyke, Anders Larsson and Per-Erik Engström

Biomedicines 2022, 10(3), 714; https://doi.org/10.3390/biomedicines10030714 - 19 Mar 2022

Cited by 4 | Viewed by 3372

Abstract

Objectives: Periodontal disease (PD) and rheumatoid arthritis (RA) are known chronic conditions with sustained inflammation leading to osteolysis. Cardiovascular diseases (CVD) are frequent comorbidities that may arise from sustained inflammation associated with both PD and RA. In order to determine CVD risk, alterations [...] Read more.

Objectives: Periodontal disease (PD) and rheumatoid arthritis (RA) are known chronic conditions with sustained inflammation leading to osteolysis. Cardiovascular diseases (CVD) are frequent comorbidities that may arise from sustained inflammation associated with both PD and RA. In order to determine CVD risk, alterations at the molecular level need to be identified. The objective of this study, therefore, was to assess the relationship of CVD associated biomarkers in RA patients and how it is influenced by PD. Methods: The study consisted of patient (26 RA with PD, 21 RA without PD, 51 patients with PD only) and systemically and periodontally healthy control (n = 20) groups. Periodontal parameters bleeding on probing, probing pocket depth, and marginal bone loss were determined to characterize the patient groups. Proteomic analysis of 92 CVD-related protein biomarkers was performed using a multiplex proximity extension assay. Biomarkers were clustered using the search tool for retrieval of interacting genes (STRING) to determine protein–protein interaction (PPI) networks. Results: RA patients with PD had higher detection levels for 47% of the measured markers (ANGPT1, BOC, CCL17, CCL3, CD4, CD84, CTRC, FGF-21, FGF-23, GLO1, HAOX1, HB-EGF, hOSCAR, HSP 27, IL16, IL-17D, IL18, IL-27, IL6, LEP, LPL, MERTK, MMP12, MMP7, NEMO, PAPPA, PAR-1, PARP-1, PD-L2, PGF, PIgR, PRELP, RAGE, SCF, SLAMF7, SRC, THBS2, THPO, TNFRSF13B, TRAIL-R2, VEGFD, VSIG2, and XCL1) as compared to RA without PD. Furthermore, a strong biological network was identified amongst these proteins (clustering coefficient = 0.52, PPI enrichment p-value < 0.0001). Coefficients for protein clusters involved in CVD (0.59), metabolic (0.53), and skeletal (0.51) diseases were strongest in the PD group. Conclusion: Periodontal disease augments CVD-related biomarkers in RA through shared pathological clusters, concurrently enhancing metabolic and skeletal disease protein interactions, independent of autoimmune status. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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Review

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18 pages, 618 KiB

Open AccessReview

Omics and Multi-Omics Analysis for the Early Identification and Improved Outcome of Patients with Psoriatic Arthritis

by Robert Gurke, Annika Bendes, John Bowes, Michaela Koehm, Richard M. Twyman, Anne Barton, Dirk Elewaut, Carl Goodyear, Lisa Hahnefeld, Rainer Hillenbrand, Ewan Hunter, Mark Ibberson, Vassilios Ioannidis, Sabine Kugler, Rik J. Lories, Eduard Resch, Stefan Rüping, Klaus Scholich, Jochen M. Schwenk, James C. Waddington, Phil Whitfield, Gerd Geisslinger, Oliver FitzGerald, Frank Behrens and Stephen R. Pennington Show full author list Hide full author list

Biomedicines 2022, 10(10), 2387; https://doi.org/10.3390/biomedicines10102387 - 24 Sep 2022

Cited by 13 | Viewed by 3781

Abstract

The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in ~30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and [...] Read more.

The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in ~30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and synovial musculoskeletal structures, but a definitive diagnosis often can only be made by clinical experts or when an extensive progressive disease state is apparent. As with other IMIDs, the detection of multimodal molecular biomarkers offers some hope for the early diagnosis of PsA and the initiation of effective management and treatment strategies. However, specific biomarkers are not yet available for PsA. The assessment of new markers by genomic and epigenomic profiling, or the analysis of blood and synovial fluid/tissue samples using proteomics, metabolomics and lipidomics, provides hope that complex molecular biomarker profiles could be developed to diagnose PsA. Importantly, the integration of these markers with high-throughput histology, imaging and standardized clinical assessment data provides an important opportunity to develop molecular profiles that could improve the diagnosis of PsA, predict its occurrence in cohorts of individuals with psoriasis, differentiate PsA from other IMIDs, and improve therapeutic responses. In this review, we consider the technologies that are currently deployed in the EU IMI2 project HIPPOCRATES to define biomarker profiles specific for PsA and discuss the advantages of combining multi-omics data to improve the outcome of PsA patients. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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22 pages, 653 KiB

Open AccessReview

Rebooting Regulatory T Cell and Dendritic Cell Function in Immune-Mediated Inflammatory Diseases: Biomarker and Therapy Discovery under a Multi-Omics Lens

by Dimitra Kerdidani, Nikos E. Papaioannou, Evangelia Nakou and Themis Alissafi

Biomedicines 2022, 10(9), 2140; https://doi.org/10.3390/biomedicines10092140 - 31 Aug 2022

Cited by 1 | Viewed by 2585

Abstract

Immune-mediated inflammatory diseases (IMIDs) are a group of autoimmune and chronic inflammatory disorders with constantly increasing prevalence in the modern world. The vast majority of IMIDs develop as a consequence of complex mechanisms dependent on genetic, epigenetic, molecular, cellular, and environmental elements, that [...] Read more.

Immune-mediated inflammatory diseases (IMIDs) are a group of autoimmune and chronic inflammatory disorders with constantly increasing prevalence in the modern world. The vast majority of IMIDs develop as a consequence of complex mechanisms dependent on genetic, epigenetic, molecular, cellular, and environmental elements, that lead to defects in immune regulatory guardians of tolerance, such as dendritic (DCs) and regulatory T (Tregs) cells. As a result of this dysfunction, immune tolerance collapses and pathogenesis emerges. Deeper understanding of such disease driving mechanisms remains a major challenge for the prevention of inflammatory disorders. The recent renaissance in high throughput technologies has enabled the increase in the amount of data collected through multiple omics layers, while additionally narrowing the resolution down to the single cell level. In light of the aforementioned, this review focuses on DCs and Tregs and discusses how multi-omics approaches can be harnessed to create robust cell-based IMID biomarkers in hope of leading to more efficient and patient-tailored therapeutic interventions. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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19 pages, 1293 KiB

Open AccessReview

Contribution of the Environment, Epigenetic Mechanisms and Non-Coding RNAs in Psoriasis

by Charalabos Antonatos, Katerina Grafanaki, Paschalia Asmenoudi, Panagiotis Xiropotamos, Paraskevi Nani, Georgios K. Georgakilas, Sophia Georgiou and Yiannis Vasilopoulos

Biomedicines 2022, 10(8), 1934; https://doi.org/10.3390/biomedicines10081934 - 09 Aug 2022

Cited by 5 | Viewed by 2826

Abstract

Despite the increasing research and clinical interest in the predisposition of psoriasis, a chronic inflammatory skin disease, the multitude of genetic and environmental factors involved in its pathogenesis remain unclear. This complexity is further exacerbated by the several cell types that are implicated [...] Read more.

Despite the increasing research and clinical interest in the predisposition of psoriasis, a chronic inflammatory skin disease, the multitude of genetic and environmental factors involved in its pathogenesis remain unclear. This complexity is further exacerbated by the several cell types that are implicated in Psoriasis’s progression, including keratinocytes, melanocytes and various immune cell types. The observed interactions between the genetic substrate and the environment lead to epigenetic alterations that directly or indirectly affect gene expression. Changes in DNA methylation and histone modifications that alter DNA-binding site accessibility, as well as non-coding RNAs implicated in the post-transcriptional regulation, are mechanisms of gene transcriptional activity modification and therefore affect the pathways involved in the pathogenesis of Psoriasis. In this review, we summarize the research conducted on the environmental factors contributing to the disease onset, epigenetic modifications and non-coding RNAs exhibiting deregulation in Psoriasis, and we further categorize them based on the under-study cell types. We also assess the recent literature considering therapeutic applications targeting molecules that compromise the epigenome, as a way to suppress the inflammatory cutaneous cascade. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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23 pages, 554 KiB

Open AccessReview

Multi-Omic Biomarkers for Patient Stratification in Sjogren’s Syndrome—A Review of the Literature

by Lucia Martin-Gutierrez, Robert Wilson, Madhura Castelino, Elizabeth C. Jury and Coziana Ciurtin

Biomedicines 2022, 10(8), 1773; https://doi.org/10.3390/biomedicines10081773 - 22 Jul 2022

Cited by 3 | Viewed by 2009

Abstract

Sjögren’s syndrome (SS) is a heterogeneous autoimmune rheumatic disease (ARD) characterised by dryness due to the chronic lymphocytic infiltration of the exocrine glands. Patients can also present other extra glandular manifestations, such as arthritis, anaemia and fatigue or various types of organ involvement. [...] Read more.

Sjögren’s syndrome (SS) is a heterogeneous autoimmune rheumatic disease (ARD) characterised by dryness due to the chronic lymphocytic infiltration of the exocrine glands. Patients can also present other extra glandular manifestations, such as arthritis, anaemia and fatigue or various types of organ involvement. Due to its heterogenicity, along with the lack of effective treatments, the diagnosis and management of this disease is challenging. The objective of this review is to summarize recent multi-omic publications aiming to identify biomarkers in tears, saliva and peripheral blood from SS patients that could be relevant for their better stratification aiming at improved treatment selection and hopefully better outcomes. We highlight the relevance of pro-inflammatory cytokines and interferon (IFN) as biomarkers identified in higher concentrations in serum, saliva and tears. Transcriptomic studies confirmed the upregulation of IFN and interleukin signalling in patients with SS, whereas immunophenotyping studies have shown dysregulation in the immune cell population frequencies, specifically CD4⁺and C8⁺T activated cells, and their correlations with clinical parameters, such as disease activity scores. Lastly, we discussed emerging findings derived from different omic technologies which can provide integrated knowledge about SS pathogenesis and facilitate personalised medicine approaches leading to better patient outcomes in the future. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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17 pages, 981 KiB

Open AccessReview

The Current Status of Molecular Biomarkers for Inflammatory Bowel Disease

by Zahra Alghoul, Chunhua Yang and Didier Merlin

Biomedicines 2022, 10(7), 1492; https://doi.org/10.3390/biomedicines10071492 - 24 Jun 2022

Cited by 18 | Viewed by 3352

Abstract

Diagnosis and prognosis of inflammatory bowel disease (IBD)—a chronic inflammation that affects the gastrointestinal tract of patients—are challenging, as most clinical symptoms are not specific to IBD, and are often seen in other inflammatory diseases, such as intestinal infections, drug-induced colitis, and monogenic [...] Read more.

Diagnosis and prognosis of inflammatory bowel disease (IBD)—a chronic inflammation that affects the gastrointestinal tract of patients—are challenging, as most clinical symptoms are not specific to IBD, and are often seen in other inflammatory diseases, such as intestinal infections, drug-induced colitis, and monogenic diseases. To date, there is no gold-standard test for monitoring IBD. Endoscopy and imaging are essential diagnostic tools that provide information about the disease’s state, location, and severity. However, the invasive nature and high cost of endoscopy make it unsuitable for frequent monitoring of disease activity in IBD patients, and even when it is possible to replace endoscopy with imaging, high cost remains a concern. Laboratory testing of blood or feces has the advantage of being non-invasive, rapid, cost-effective, and standardizable. Although the specificity and accuracy of laboratory testing alone need to be improved, it is increasingly used to monitor disease activity or to diagnose suspected IBD cases in combination with endoscopy and/or imaging. The literature survey indicates a dearth of summarization of biomarkers for IBD testing. This review introduces currently available non-invasive biomarkers of clinical importance in laboratory testing for IBD, and discusses the trends and challenges in the IBD biomarker studies. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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17 pages, 1642 KiB

Open AccessReview

by Nieves Peltzer and Alessandro Annibaldi

Biomedicines 2022, 10(6), 1436; https://doi.org/10.3390/biomedicines10061436 - 17 Jun 2022

Cited by 1 | Viewed by 2812

Abstract

Aberrant cell death can cause inflammation and inflammation-related diseases. While the link between cell death and inflammation has been widely established in mouse models, evidence supporting a role for cell death in the onset of inflammatory and autoimmune diseases in patients is still [...] Read more.

Aberrant cell death can cause inflammation and inflammation-related diseases. While the link between cell death and inflammation has been widely established in mouse models, evidence supporting a role for cell death in the onset of inflammatory and autoimmune diseases in patients is still missing. In this review, we discuss how the lessons learnt from mouse models can help shed new light on the initiating or contributing events leading to immune-mediated disorders. In addition, we discuss how multiomic approaches can provide new insight on the soluble factors released by dying cells that might contribute to the development of such diseases. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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18 pages, 868 KiB

Open AccessReview

Novel Biomarkers, Diagnostic and Therapeutic Approach in Rheumatoid Arthritis Interstitial Lung Disease—A Narrative Review

by Alesandra Florescu, Florin Liviu Gherghina, Anca Emanuela Mușetescu, Vlad Pădureanu, Anca Roșu, Mirela Marinela Florescu, Cristina Criveanu, Lucian-Mihai Florescu and Anca Bobircă

Biomedicines 2022, 10(6), 1367; https://doi.org/10.3390/biomedicines10061367 - 09 Jun 2022

Cited by 12 | Viewed by 3739

Abstract

Rheumatoid arthritis (RA) is considered a systemic inflammatory disease marked by polyarthritis which affects the joints symmetrically, leading to progressive damage of the bone structure and eventually joint deformity. Lung involvement is the most prevalent extra-articular feature of RA, affecting 10–60% of patients [...] Read more.

Rheumatoid arthritis (RA) is considered a systemic inflammatory disease marked by polyarthritis which affects the joints symmetrically, leading to progressive damage of the bone structure and eventually joint deformity. Lung involvement is the most prevalent extra-articular feature of RA, affecting 10–60% of patients with this disease. In this review, we aim to discuss the patterns of RA interstitial lung disease (ILD), the molecular mechanisms involved in the pathogenesis of ILD in RA, and also the therapeutic challenges in this particular extra-articular manifestation. The pathophysiology of RA-ILD has been linked to biomarkers such as anti-citrullinated protein antibodies (ACPAs), MUC5B mutation, Krebs von den Lungen 6 (KL-6), and other environmental factors such as smoking. Patients at the highest risk for RA-ILD and those most likely to advance will be identified using biomarkers. The hope is that finding biomarkers with good performance characteristics would help researchers better understand the pathophysiology of RA-ILD and, in turn, lead to the development of tailored therapeutics for this severe RA manifestation. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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12 pages, 876 KiB

Open AccessSystematic Review

Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review

by Rajalingham Sakthiswary, Syahrul Sazliyana Shaharir and Asrul Abdul Wahab

Biomedicines 2022, 10(3), 558; https://doi.org/10.3390/biomedicines10030558 - 26 Feb 2022

Cited by 5 | Viewed by 2242

Abstract

Immunoglobulin (Ig)G4 is a unique protein molecule and its role in autoimmune diseases remains elusive and controversial. Accumulating evidence suggests a pathogenic role of IgG4 in rheumatoid arthritis (RA). Rheumatoid factors (RF) in RA can recognize the Fc domains of IgG4 to form [...] Read more.

Immunoglobulin (Ig)G4 is a unique protein molecule and its role in autoimmune diseases remains elusive and controversial. Accumulating evidence suggests a pathogenic role of IgG4 in rheumatoid arthritis (RA). Rheumatoid factors (RF) in RA can recognize the Fc domains of IgG4 to form RF-IgG4 immune complexes that may activate the complement system leading to synovial injury. The aim of this article was to systematically review the literature from the past 2 decades to determine the frequency of elevated IgG4 and its clinical significance in RA. We comprehensively searched the Pubmed, Scopus, and Web of Science databases with the following terms: “IgG4”, “rheumatoid arthritis”, and “immunoglobulin G4”, and scrutinized all of the relevant publications. Based on the selection criteria, 12 studies were incorporated, which involved a total of 1715 RA patients. Out of 328 subjects from three studies, the pooled frequency of elevated non-specific IgG4 was 35.98%. There was a significant positive correlation between the IgG4 levels and the RA disease activity based on DAS-28 measurements (r = 0.245–0.253) and inflammatory markers, i.e., erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels (r = 0.262–0.389). Longitudinal studies that measured the serial levels of IgG4 consistently showed a decline in the concentrations (up to 48% less than baseline) with disease modifying anti-rheumatic drug (DMARD) treatment. Current evidence suggests that serum IgG4 levels are significantly elevated in RA compared to the general population. This review indicates that IgG4 is a promising biomarker of disease activity and tends to decline in response to DMARD therapies. Biologic therapies have revolutionized the therapeutic armamentarium of RA in the recent decade, and IgG4 appears to be a potential treatment target. Full article

(This article belongs to the Special Issue Omics Approaches to Immune-Mediated Inflammatory Diseases: Towards Novel Biomarkers and Potential Therapeutic Targets)

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