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Life
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New Insights in Autoimmune Arthritis and Nephritis
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New Insights in Autoimmune Arthritis and Nephritis

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (10 December 2021) | Viewed by 21273

Special Issue Editors

Dr. Yuji Nozaki

E-Mail Website
Guest Editor
Division of Hematology and Rheumatology, Faculty of Medicine, Kinki University, 2-377 Ohno-Higashi, Osaka-Sayama, Osaka, Japan
Interests: cytokine; renal disease; rheumatoid arthritis; autoimmune disease; biological agents
Dr. Poh Yi Gan

E-Mail Website
Guest Editor
Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, VIC 3168, Australia
Interests: immunomodulation; ANCA vasculitis; T regulatory cells; mast cells; glomerulonephritis; acute kidney injury; nanoparticle
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The immune response system has a central role in eliminating detrimental factors by frequently launching inflammatory responses towards pathogen infection and inner danger signal outbreak. Acute and chronic inflammatory responses are critical determinants for consequences of inflammatory arthritis and nephritis, in which cytokine network systems were inevitably involved. Cytokines are small, secreted proteins associated with the maintenance of immune homeostasis but also implicated with the pathogenesis of several autoimmune and inflammatory diseases. The signal transduction originating from membrane-bound cytokine receptors is an intricate network of events that lead to gene expression and ultimately regulate cellular functionality. Our understanding of the intracellular actions that molecules such as interleukins, interferons, and tumor necrosis factor set into motion has greatly increased in the past few years, making it possible to interfere with cytokines’ signaling cascades. The Janus kinase/signal transducer and activator of transcription, the nuclear factor kappa-light-chain-enhancer of activated B cells, the mitogen-activated protein kinase and the Phosphatidylinositol-3'-kinases pathways have all been intensively studied, and key steps as well as molecules have been identified. These research efforts have led to the development of a new generation of small molecule inhibitors. Therefore, challenges in autoimmune arthritis and nephritis include continuing to improve the advances in pathogenesis and molecular biology, and novel therapeutic options.

This Research Topic aims to discuss the cytokine network in terms of pathological processes. It will be crucial to select cytokine targets based not on one single inflammatory pathway but rather on a biosystematic approach to pathogenesis. Implicit in this will be the recognition of pivotal checkpoints that facilitate the progression from autoimmunity to chronic inflammation in autoimmune arthritis and nephritis.

Dr. Yuji Nozaki
Dr. Poh Yi Gan
Guest Editors

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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 2600 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

  • autoimmune arthritis
  • autoimmune nephritis
  • Inflammatory diseases
  • human and animal models

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Published Papers (7 papers)

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Research

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10 pages, 244 KiB  
Article
The Effect of Tocilizumab on Inflammatory Markers in Patients Hospitalized with Serious Infections. Case Series and Review of Literature
by Mark Berman, Ronen Ben-Ami, Shlomo Berliner, Marina Anouk, Ilana Kaufman, Adi Broyde, Sara Borok and Ori Elkayam
Life 2021, 11(3), 258; https://doi.org/10.3390/life11030258 - 20 Mar 2021
Cited by 20 | Viewed by 3370
Abstract
Background: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results [...] Read more.
Background: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results when accessing the patient with infectious disease while on TCZ. We conducted this study to report cases treated with tocilizumab who developed serious infections with special reference to levels of CRP and to review the literature on the effect of tocilizumab on acute phase response (APR) during infections. Methods: The files of RA and GCA patients hospitalized in the Tel Aviv medical center between 2009–2019 were reviewed. Cases of patients with RA and GCA treated with tocilizumab who were hospitalized due to severe infections were reviewed with special emphasis on the duration of treatment, type of infection, and APR. Results: We identified nine admissions. Seven patients were treated with tocilizumab for RA, two for GCA. The diagnosis was pneumonia in three cases, osteomyelitis in one, cellulitis in one, endocarditis due to Whipple disease in one, abscess of cervix uteri in one, meningitis in one, and perforated diverticulitis in one. The mean CRP levels on admission were 4.75 mg/L (normal range, up to 5 mg/L). All cases were diagnosed correctly on admission. Conclusions: CRP levels may not correctly reflect the severity of infectious diseases during tocilizumab treatment. Increased awareness of the masking effect of tocilizumab on the APR during infection is needed in order to avoid a delay in the diagnosis. Full article
(This article belongs to the Special Issue New Insights in Autoimmune Arthritis and Nephritis)
9 pages, 2379 KiB  
Article
The Role of Clinical and Ultrasound Enthesitis Scores in Ankylosing Spondylitis
by Alesandra Florescu, Vlad Pădureanu, Dan Nicolae Florescu, Anca Bobircă, Lucian-Mihai Florescu, Ana-Maria Bumbea, Rodica Pădureanu and Anca Emanuela Mușetescu
Life 2021, 11(3), 218; https://doi.org/10.3390/life11030218 - 9 Mar 2021
Cited by 9 | Viewed by 2626
Abstract
Introduction: Ankylosing spondylitis (AS) is a chronic inflammatory disease, part of the spondyloarthritis (SpA) group, characterized by axial (spine and sacroiliac joints), entheseal, and peripheral joint involvement, which is frequently associated with extra-articular manifestations. Material and Methods: The study included a number of [...] Read more.
Introduction: Ankylosing spondylitis (AS) is a chronic inflammatory disease, part of the spondyloarthritis (SpA) group, characterized by axial (spine and sacroiliac joints), entheseal, and peripheral joint involvement, which is frequently associated with extra-articular manifestations. Material and Methods: The study included a number of 30 patients diagnosed with AS according to the New York modified criteria, with history of entheseal pain, hospitalized between 2016–2018 in the Department of Rheumatology of the Emergency County Hospital of Craiova. Results: Regarding the Belgrade Ultrasound Enthesitis Score (BUSES) score and the disease activity calculated using the Ankylosing Spondylitis Disease Activity Score (ASDAS), they did not show a statistically significant association (p = 0.738). Additionally, BUSES did not have a statistically significant association with the disease activity quantified by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score (p = 0.094). The Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC) clinical score was not statistically associated with ASDAS (p = 0.434) nor with BASDAI (p = 0.130). The SPARCC clinical score and the BUSES ultrasound score were statistically significantly associated, registering a value of p = 0.018. Conclusions: Our study proved a significant correlation between SPARCC and BUSES, although in literature the evidence is contrasting. Full article
(This article belongs to the Special Issue New Insights in Autoimmune Arthritis and Nephritis)
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11 pages, 914 KiB  
Article
The Effectiveness and Retention Rate of Iguratimod in Japanese Rheumatoid Arthritis Patients with/without Methotrexate in Daily Medical Care
by Asuka Inoue, Yuji Nozaki, Yasuaki Hirooka, Koji Kinoshita, Yasutaka Chiba, Masanori Funauchi and Itaru Matsumura
Life 2020, 10(11), 261; https://doi.org/10.3390/life10110261 - 29 Oct 2020
Cited by 4 | Viewed by 2493
Abstract
(1) Background: We evaluated the clinical response of iguratimod (IGU) in patients with rheumatoid arthritis (RA) being treated with or without methotrexate (MTX) over 54 weeks. (2) Methods: 106 patients with RA undergoing IGU were retrospectively observed. RA patients were divided into those [...] Read more.
(1) Background: We evaluated the clinical response of iguratimod (IGU) in patients with rheumatoid arthritis (RA) being treated with or without methotrexate (MTX) over 54 weeks. (2) Methods: 106 patients with RA undergoing IGU were retrospectively observed. RA patients were divided into those treated with MTX+IGU (n = 35) and those treated with IGU (n = 71). The primary endpoint was the clinical response of the Disease Activity Score assessing 28 joints with C-reactive protein (DAS28-CRP) differences in the changes from baseline to 54 weeks between MTX+IGU and IGU groups. Secondary endpoints, such as the clinical response, retention rate, and safety, were evaluated. (3) Results: The DAS28-CRP difference in the changes between the two groups were −0.2. DAS28-CRP were significantly reduced from the baseline in the MTX+IGU and IGU groups (−1.43 and −1.20 from baseline, respectively). The retention rates were 71.4% in the MTX+IGU groups and 59.2% in the IGU groups (p = 0.16). Adverse events were observed in a total of 6 (17.1%) MTX+IGU patients and 20 (28.2%) IGU patients (p = 0.21). (4) Conclusions: IGU therapy may be a useful treatment option for patients who cannot be treated with MTX. Full article
(This article belongs to the Special Issue New Insights in Autoimmune Arthritis and Nephritis)
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Review

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9 pages, 590 KiB  
Review
Iguratimod: Novel Molecular Insights and a New csDMARD for Rheumatoid Arthritis, from Japan to the World
by Yuji Nozaki
Life 2021, 11(5), 457; https://doi.org/10.3390/life11050457 - 20 May 2021
Cited by 15 | Viewed by 4633
Abstract
Iguratimod (IGU) is a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) routinely prescribed in Japan since 2012 to patients with rheumatoid arthritis (RA). Iguratimod acts directly on B cells by inhibiting the production of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, IL-17), [...] Read more.
Iguratimod (IGU) is a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) routinely prescribed in Japan since 2012 to patients with rheumatoid arthritis (RA). Iguratimod acts directly on B cells by inhibiting the production of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, IL-17), thereby suppressing the production of immunoglobulin and inhibiting the activity of nuclear factor kappa-light chain enhancer of activated B cells. In Japan, it is one of the most used csDMARDs in daily practice, but it is not recommended as a treatment for RA due to the lack of large-scale evidence established overseas. However, recent reports on the novel pharmacological effects of IGU on lymphocytes and synovial fibroblasts, as well as its efficacy in daily practice, have increased its importance as a drug for the treatment of RA. In this review, we highlighted the basic and clinical studies in IGU and discuss its potential as a new therapeutic agent for the treatment of RA. Full article
(This article belongs to the Special Issue New Insights in Autoimmune Arthritis and Nephritis)
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Other

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7 pages, 4862 KiB  
Case Report
Takayasu’s Arteritis Diagnosed in an Adolescent Patient with Crohn’s Disease: Management of Biologicals
by Kazuya Kishimoto, Yuji Nozaki, Toshiharu Sakurai, Koji Kinoshita, Masanori Funauchi and Itaru Matsumura
Life 2021, 11(10), 1019; https://doi.org/10.3390/life11101019 - 28 Sep 2021
Cited by 2 | Viewed by 2819
Abstract
We report a 14-year-old man with Crohn’s disease (CD) who developed right upper arm pain while being treated with the anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, infliximab. There were no symptoms suggestive of active CD, but the inflammatory response was high, and a [...] Read more.
We report a 14-year-old man with Crohn’s disease (CD) who developed right upper arm pain while being treated with the anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, infliximab. There were no symptoms suggestive of active CD, but the inflammatory response was high, and a contrast-enhanced CT showed the occlusion of the right brachial artery. We diagnosed the patient as having Takayasu’s arteritis (TA) and started treatment with corticosteroids, then tapered off the steroids as the symptoms of TA resolved. Later, TA flared up, and his treatment was changed from infliximab to an anti-IL-6 receptor antibody, tocilizumab. The change to TCZ stabilized TA, but exacerbated CD. It is difficult to control both diseases at the same time, and the choice of biologics for treatment must be carefully considered. Full article
(This article belongs to the Special Issue New Insights in Autoimmune Arthritis and Nephritis)
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7 pages, 2984 KiB  
Case Report
FDG-PET/CT and Auricular Cartilage Biopsy Are Useful for Diagnosing with Relapsing Polychondritis in Patients without Auricular Symptoms
by Saki Okuda, Yasuaki Hirooka, Tetsu Itami, Yuji Nozaki, Masafumi Sugiyama, Koji Kinoshita, Masanori Funauchi and Itaru Matsumura
Life 2021, 11(9), 956; https://doi.org/10.3390/life11090956 - 13 Sep 2021
Cited by 7 | Viewed by 2273
Abstract
Relapsing polychondritis (RP) is a rare autoimmune inflammatory disease characterized by recurrent inflammation and destruction of cartilage. Although auricular chondritis is a characteristic finding in RP, it can be difficult to diagnose in the absence of auricular symptoms. A 64-year-old Japanese male was [...] Read more.
Relapsing polychondritis (RP) is a rare autoimmune inflammatory disease characterized by recurrent inflammation and destruction of cartilage. Although auricular chondritis is a characteristic finding in RP, it can be difficult to diagnose in the absence of auricular symptoms. A 64-year-old Japanese male was referred to our hospital with fever and respiratory distress. Contrast-enhanced computed tomography (CT) revealed bronchial wall thickening and we suspected RP; however, he had no auricular symptoms and did not meet the diagnostic McAdam criteria for RP, so we used 18F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) to search for other cartilage lesions. This analysis revealed FDG accumulation not only in the bronchial walls, but also in the left auricle. Instead of a bronchial biopsy using a bronchoscope, we performed a biopsy of the left auricular cartilage, which is considered a relatively less invasive site. Even though the auricle was asymptomatic, the pathology results revealed chondritis. He was diagnosed with RP, and his symptoms rapidly improved with corticosteroid therapy. A biopsy of asymptomatic auricular cartilage may be useful in the diagnosis of RP. FDG-PET/CT is a powerful tool for the early diagnosis of RP, identifying inflammatory areas even in the absence of symptoms, and guiding the selection of appropriate biopsy sites. Full article
(This article belongs to the Special Issue New Insights in Autoimmune Arthritis and Nephritis)
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6 pages, 3040 KiB  
Case Report
Antiretroviral Therapy Improves Acquired Immunodeficiency Syndrome with Systemic Lupus Erythematosus
by Akinori Okada, Yuji Nozaki, Shinya Rai, Koji Kinoshita, Masanori Funauchi and Itaru Matsumura
Life 2021, 11(6), 463; https://doi.org/10.3390/life11060463 - 21 May 2021
Cited by 1 | Viewed by 2055
Abstract
A 35-year-old male was referred to our hospital with dysesthesia of the lower extremities that had begun six months earlier. A blood test revealed the presence of various antibodies, suggesting a collagen-related peripheral neuropathy. However, a history of repeated shingles and sex with [...] Read more.
A 35-year-old male was referred to our hospital with dysesthesia of the lower extremities that had begun six months earlier. A blood test revealed the presence of various antibodies, suggesting a collagen-related peripheral neuropathy. However, a history of repeated shingles and sex with males was noted, and the patient was tested for and diagnosed with human immunodeficiency virus (HIV) infection. Based on the manifestations and laboratory data, including the results of immunological and urinary tests, he was further diagnosed with concomitant systemic lupus erythematosus (SLE). The activity of SLE improved with antiretroviral therapy. There is currently no established treatment for AIDS complicated with SLE. Indeed, because HIV treatment involves the activation of immune function and SLE treatment involves immunosuppression, any treatments for the two conditions would be in conflict. It is thus necessary to select a treatment strategy based on the condition of the individual patient. In addition, because HIV infection is relatively rare in Japan compared to other countries, rheumatologists in Japan must keep HIV infection in mind as a differential diagnosis for autoimmune diseases. Full article
(This article belongs to the Special Issue New Insights in Autoimmune Arthritis and Nephritis)
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