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New Insights into the Pathogenesis and Treatment of Inflammatory Rheumatic Diseases

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (20 April 2022) | Viewed by 18043

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Dr. Luca Quartuccio

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Guest Editor

Clinic of Rheumatology, Department of Medicine (DAME), Academic Hospital "Santa Maria della Misericordia", Udine, Italy
Interests: vasculitis; arthritis; biologic treatment; B-cell; cryoglobulinemia; sjogren's syndrome
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Special Issue Information

Dear Colleagues,

The knowledge in inflammatory rheumatic diseases is constantly growing both regarding the pathogenesis and, then, the treatment. For example, the efficacy of Janus kinase inhibitors in many autoimmune inflammatory diseases has highlighted the role of new pathways in chronic inflammation and autoimmunity. Moreover, genetic studies are changing the landscape of the autoimmune diseases from a clinical and serological definition to a biologic and molecular characterization, opening the way to novel treatment strategies with new but also old drugs currently employed in diseases other than rheumatic ones. Therefore, the scope of this Special Issue is to link the novelty in the pathogenesis to the good news in the treatment of several inflammatory rheumatic diseases, and to move towards novel insights into the future treatments of rheumatic conditions, based on the most recent scientific discoveries.

Dr. Luca Quartuccio
Guest Editor

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Keywords

Pathogenesis
Therapy
B-cell
T-cell
Immunity
Cytokine
Inflammation
Arthritis
Vasculitis
Connective tissue diseases

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Published Papers (5 papers)

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Research

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17 pages, 5128 KiB

Open AccessArticle

Adiponectin Is a Component of the Inflammatory Cascade in Rheumatoid Arthritis

by Małgorzata Łączna, Patrycja Kopytko, Marta Tkacz, Katarzyna Zgutka, Michał Czerewaty, Maciej Tarnowski, Dariusz Larysz, Rafał Tkacz, Daniel Kotrych, Katarzyna Piotrowska, Krzysztof Safranow, Karolina Łuczkowska, Bogusław Machaliński and Andrzej Pawlik

J. Clin. Med. 2022, 11(10), 2740; https://doi.org/10.3390/jcm11102740 - 12 May 2022

Cited by 11 | Viewed by 2003

Abstract

Adiponectin is a secretory protein of adipocytes that plays an important role in pathological processes by participation in modulating the immune and inflammatory responses. The pro-inflammatory effect of adiponectin is observed in rheumatoid arthritis (RA). In this study, we examined adiponectin plasma levels and the expression of adiponectin in bone marrow tissue samples, synovium samples, and infrapatellar fat pad samples from patients with osteoarthritis (OA) and RA. Additionally we examined the expression of adiponectin receptors AdipoR1 and AdipoR2 in synovium samples and infrapatellar fat pad samples from patients with OA and RA. We also assessed the correlations between adiponectin plasma concentrations, adiponectin expression in bone marrow, synovium, infrapatellar fat pad, and plasma levels of selected cytokines. We found increased expression of adiponectin in synovium samples and infrapatellar fat pad samples from patients with RA as compared to patients with OA. There were no statistically significant differences of adiponectin plasma levels and adiponectin expression in bone marrow tissue samples between OA and RA patients. There were no differences in the expression of AdipoR1 and AdipoR2 at the mRNA level in synovial tissue and the infrapatellar fat pad between RA and OA patients. However, in immunohistochemical analysis in samples of the synovial membrane from RA patients, we observed very strong expression of adiponectin in intima cells, macrophages, and subintimal fibroblasts, such as synoviocytes, vs. strong expression in OA samples. Very strong expression of adiponectin was also noted in adipocytes of Hoffa’s fat pad of RA patients. Expression of AdipoR1 was stronger in RA tissue samples, while AdipoR2 expression was very similar in both RA and OA samples. Our results showed increased adiponectin expression in the synovial membrane and Hoffa’s pad in RA patients compared to that of OA patients. However, there were no differences in plasma adiponectin concentrations and its expression in bone marrow. The results suggest that adiponectin is a component of the inflammatory cascade that is present in RA. Pro-inflammatory factors enhance the expression of adiponectin, especially in joint tissues—the synovial membrane and Hoffa’s fat pad. In turn, adiponectin also increases the expression of further pro-inflammatory mediators. Full article

(This article belongs to the Special Issue New Insights into the Pathogenesis and Treatment of Inflammatory Rheumatic Diseases)

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6 pages, 224 KiB

Open AccessArticle

Association between Androgen Deprivation Therapy and the Risk of Inflammatory Rheumatic Diseases in Men with Prostate Cancer: Nationwide Cohort Study in Lithuania

by Mingaile Drevinskaite, Jolanta Dadoniene, Dalia Miltiniene, Ausvydas Patasius and Giedre Smailyte

J. Clin. Med. 2022, 11(7), 2039; https://doi.org/10.3390/jcm11072039 - 5 Apr 2022

Cited by 4 | Viewed by 1863

Abstract

Background: The aim of this study was to assess the association between androgen deprivation therapy (ADT) and the risk of inflammatory rheumatic diseases in men with prostate cancer. Methods: Patients with prostate cancer between 2012 and 2016 were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database, on the basis of rheumatic diseases diagnoses and information on prescriptions for androgen deprivation therapy. Cox proportional hazard models were used to estimate hazard ratios (HR) to compare the risks of rheumatic diseases caused by androgen deprivation therapy exposure in groups of prostate cancer patients. Results: A total of 12,505 prostate cancer patients were included in this study, out of whom 3070 were ADT users and 9390 were ADT non-users. We observed a higher risk of rheumatic diseases in the cohort of prostate cancer patients treated with ADT compared with ADT non-users (HR 1.55, 95% confidence interval (CI) 1.01–2.28). Detailed risk by cumulative use of ADT was performed for rheumatoid arthritis, and a statistically significant higher risk was found in the group with longest cumulative ADT exposure (>105 weeks) (HR 3.18, 95% CI 1.39–7.29). Conclusions: Our study suggests that ADT usage could be associated with increased risk of rheumatoid arthritis, adding to the many known side effects of ADT. Full article

(This article belongs to the Special Issue New Insights into the Pathogenesis and Treatment of Inflammatory Rheumatic Diseases)

10 pages, 256 KiB

Open AccessArticle

Genetic Polymorphisms of GGH and ABCC2 Are Associated with Methotrexate Intolerance in Patients with Rheumatoid Arthritis

by Alejandro Escudero-Contreras, Clementina López-Medina, Eduardo Collantes-Estévez, Rafaela Ortega-Castro, Jerusalem Calvo-Gutiérrez, Natalia Mena-Vázquez, Blanca Panero-Lamothe, Bárbara Manzanares-Martín, Rafael Cáliz-Cáliz, Alberto Jiménez-Morales, Mayte Ruiz-Jiménez and Pilar Font-Ugalde

J. Clin. Med. 2021, 10(18), 4070; https://doi.org/10.3390/jcm10184070 - 9 Sep 2021

Cited by 1 | Viewed by 2236

Abstract

Objective: to identify new single-nucleotide polymorphisms (SNPs) in genes encoding proteins involved in methotrexate (MTX) metabolism and to evaluate the associations of these SNPs with MTX toxicity or intolerance in a southern Spanish cohort of patients with rheumatoid arthritis (RA). Methods: An observational, retrospective, and multicenter study was conducted at three participating hospitals in southern Spain. The main variable was intolerance to MTX (i.e., bDMARD monotherapy), defined as an interruption of treatment due to adverse events or toxicity. Patients being treated with MTX and bDMARDs (combined treatment) at the time of the study visit were considered “tolerant” of MTX. Ten polymorphisms were selected for sequencing in our patients according to a literature review. Each polymorphism was classified according to three possible genotypes (e.g., two homozygous (AA or GG) and one heterozygous (AG)), and the association of these combinations with MTX intolerance was evaluated. Results: A total of 227 patients were included in the final analysis (107 intolerant of MTX and 120 tolerant). A significant association was observed between MTX intolerance and the GGH-T401C AA/AG genotype (OR 2.13, 95% CI 1.06–4.29) in comparison with the GG genotype. On the other hand, an inverse association was observed between the ABCC2-C24T TT/TC genotype and intolerance to MTX (OR 0.59, 95% CI 0.35–1.00) in comparison with the CC genotype. Conclusion: This study provides new data on the association between genetic polymorphisms and MTX intolerance, which may contribute to the development of new biomarkers and personalized medicine in patients with RA. Full article

(This article belongs to the Special Issue New Insights into the Pathogenesis and Treatment of Inflammatory Rheumatic Diseases)

13 pages, 249 KiB

Open AccessArticle

Prevalence of Newly Diagnosed Malignancies in Patients with Polymyalgia Rheumatica and Giant Cell Arteritis, Comparison of 18F-FDG PET/CT Scan with Chest X-ray and Abdominal Ultrasound: Data from a 40 Week Prospective, Exploratory, Single Centre Study

by Amir Emamifar, Søren Hess, Torkell Ellingsen, Susan Due Kay, Jacob Christian Bang, Oke Gerke, Per Syrak Hansen, Ziba Ahangarani Farahani, Henrik Petersen, Niels Marcussen, Inger Marie Jensen Hansen and Peter Thye Rønn

J. Clin. Med. 2020, 9(12), 3940; https://doi.org/10.3390/jcm9123940 - 4 Dec 2020

Cited by 13 | Viewed by 2595

Abstract

The aim of the study was to identify the prevalence of newly diagnosed malignancies in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), with the aid of 18F-FDG PET/CT scan compared to conventional imaging techniques: Chest X-ray (CXR) and abdominal ultrasound (US). Secondarily, to examine the relative diagnostic accuracy of these two imaging modalities for the detection of cancer. Eighty consecutive patients with newly diagnosed PMR, GCA, or concomitant PMR and GCA, were included and followed up for 40 weeks. All patients underwent an 18F-FDG PET/CT scan, CXR, and abdominal US at diagnosis. Imaging findings were dichotomously categorized into malignant or benign. Among 80 patients, three patients were diagnosed with seronegative rheumatoid arthritis and were excluded from the analysis. Of the remaining 77, 64 (83.1%) patients were diagnosed with pure PMR, 3 (3.9%) with pure GCA, and 10 (13.0%) with concomitant PMR and GCA. Five types of cancer that were more prevalent than the one-year prevalence of 1.2% among the background population were found in four (5.2%; 95%CI: 1.4–12.8%) patients. CXR/abdominal US could detect the solid cancer in one patient, whereas 18F-FDG PET/CT could identify all four solid cancers. Furthermore, four (5.2%; 95%CI: 1.4–12.8%) cases of monoclonal gammopathy of undetermined significance (MGUS) were found. An increase in C reactive protein (CRP) implicated an increased risk for cancer of 2.4% (OR: 1.024, 95%CI: 1.001–1.047; p = 0.041). 18F-FDG PET/CT can reveal occult cancers at an early stage with a high negative predictive value, and it is specifically beneficial in PMR/GCA patients with nonspecific symptoms. Full article

(This article belongs to the Special Issue New Insights into the Pathogenesis and Treatment of Inflammatory Rheumatic Diseases)

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25 pages, 418 KiB

Open AccessReview

Bruton’s Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives

by Ewa Robak and Tadeusz Robak

J. Clin. Med. 2022, 11(10), 2807; https://doi.org/10.3390/jcm11102807 - 16 May 2022

Cited by 34 | Viewed by 8427

Abstract

The use of Bruton’s tyrosine kinase (BTK) inhibitors has changed the management of patients with B-cell lymphoid malignancies. BTK is an important molecule that interconnects B-cell antigen receptor (BCR) signaling. BTK inhibitors (BTKis) are classified into three categories, namely covalent irreversible inhibitors, covalent reversible inhibitors, and non-covalent reversible inhibitors. Ibrutinib is the first covalent, irreversible BTK inhibitor approved in 2013 as a breakthrough therapy for chronic lymphocytic leukemia patients. Subsequently, two other covalent, irreversible, second-generation BTKis, acalabrutinib and zanubrutinib, have been developed for lymphoid malignancies to reduce the ibrutinib-mediated adverse effects. More recently, irreversible and reversible BTKis have been under development for immune-mediated diseases, including autoimmune hemolytic anemia, immune thrombocytopenia, multiple sclerosis, pemphigus vulgaris, atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease, and chronic spontaneous urticaria, among others. This review article summarizes the preclinical and clinical evidence supporting the role of BTKis in various autoimmune, allergic, and inflammatory conditions. Full article

(This article belongs to the Special Issue New Insights into the Pathogenesis and Treatment of Inflammatory Rheumatic Diseases)

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