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Biomolecules
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Biomarkers in Systemic Lupus Erythematosus
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Biomarkers in Systemic Lupus Erythematosus

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biomarkers".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 19213

Special Issue Editor

Prof. Dr. Yosiyha Tanaka

E-Mail Website
Guest Editor
The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555, Japan
Interests: rheumatoid arthritis; antirheumatic agents; systemic lupus erythematosus

Special Issue Information

Dear Colleagues,

Systemic lupus erythematosus (SLE) is a representative systemic autoimmune disease that damages various organs throughout the body such as the skin, joints, kidneys, serosa, lungs, central nerves, and hematopoietic system, among others. Although treatment has gradually progressed in concordance with the elucidation of the pathophysiology, the delay in the development of molecular-targeted therapies is remarkable compared to rheumatoid arthritis and psoriasis. Successful development of new treatments for these diseases is impossible without a standard “ruler” that can allow for the accurate and objective evaluation of disease activity, pathophysiology, and treatment responsiveness. A biomarker with excellent versatility, economy, and reproducibility is preferred, and a biomarker suitable for application in the context of pathological mechanisms and treatment is expected to be a more useful “ruler”. Furthermore, GWAS has expanded such biomarkers from application at the protein to the genome level. This Special Issue will cover rationales for SLE diagnosis, assistance for differential diagnosis, classification of disease type, evaluation of organ disorders, estimation of disease activity, rationales for treatment selection, prediction of treatment response, outcomes of treatment, and prognosis. Experts on the frontlines of the world will provide an overview of the biomarkers that are currently used or expected to be used in the future for SLE. We hope that readers will engage with the new trend in SLE research and treatment in establishing a useful “ruler”.

Prof. Dr. Yosiyha Tanaka
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 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

  • systemic lupus erythematosus
  • lupus nephritis
  • biomarker
  • diagnosis
  • treatments

Published Papers (7 papers)

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Research

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11 pages, 808 KiB  
Article
Relationship of Fibroblast Growth Factor 23 Serum Levels with Disease Characteristics in Systemic Lupus Erythematosus Patients
by Yolanda Fernández-Cladera, Fuensanta Gómez-Bernal, María García-González, Juan C. Quevedo-Abeledo, Agustín F. González-Rivero, Antonia de Vera-González, Candelaria Martín-González, Ana L. Nunes-Andrade, Raquel López-Mejías, Miguel Á. González-Gay and Iván Ferraz-Amaro
Biomolecules 2023, 13(8), 1222; https://doi.org/10.3390/biom13081222 - 5 Aug 2023
Viewed by 1814
Abstract
Fibroblast growth factor 23 (FGF23), a hormone secreted by osteocytes and osteoblasts, is a major regulator of vitamin D and phosphate homeostasis. FGF23 has been associated with the disturbance of mineral homeostasis, and with kidney and cardiovascular diseases. Systemic lupus erythematosus (SLE) is [...] Read more.
Fibroblast growth factor 23 (FGF23), a hormone secreted by osteocytes and osteoblasts, is a major regulator of vitamin D and phosphate homeostasis. FGF23 has been associated with the disturbance of mineral homeostasis, and with kidney and cardiovascular diseases. Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect virtually any organ. In the present work, we set out to analyze the relationship of FGF23 with the expression of SLE, including patterns of activity, damage, and severity. A total of 284 well-characterized patients with SLE were recruited. Activity (SLEDAI), severity (Katz), and damage index (SLICC-DI) scores were determined. The serum levels of FGF23 were also assessed. Multivariable linear regression analysis was performed to study the relationship between disease characteristics and FGF23. FGF23 and 25(OH) vitamin D were negatively correlated. Furthermore, prednisone use was associated with higher circulating FGF23 after an adjustment for confounding factors. SLICC-DI was related to higher serum levels of FGF23 after a multivariable analysis. However, when the SLICC-DI index items and domains were analyzed separately, apart from proteinuria ≥3.5 gm/24 h, only the musculoskeletal domain, encompassing arthritis and osteoporosis, was significantly associated with higher serum levels of FGF23. In conclusion, an association is observed between elevated serum FGF23 levels and disease damage, particularly related to musculoskeletal complications and proteinuria, in patients with SLE. Full article
(This article belongs to the Special Issue Biomarkers in Systemic Lupus Erythematosus)
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12 pages, 287 KiB  
Article
Increased Serum Interleukin 10 Levels Are Associated with Increased Disease Activity and Increased Risk of Anti-SS-A/Ro Antibody Positivity in Patients with Systemic Lupus Erythematosus
by Agnieszka Winikajtis-Burzyńska, Marek Brzosko and Hanna Przepiera-Będzak
Biomolecules 2023, 13(6), 974; https://doi.org/10.3390/biom13060974 - 11 Jun 2023
Cited by 2 | Viewed by 1619
Abstract
Interleukin 10 (IL-10) plays a role in inflammation and cell-type responses. The anti-SS-A/Ro antibody contributes to leucopenia, and cutaneous and neonatal lupus. Objectives: To evaluate the association between serum IL-10 levels and autoantibodies, disease activity and organ involvement in systemic lupus erythematosus (SLE) [...] Read more.
Interleukin 10 (IL-10) plays a role in inflammation and cell-type responses. The anti-SS-A/Ro antibody contributes to leucopenia, and cutaneous and neonatal lupus. Objectives: To evaluate the association between serum IL-10 levels and autoantibodies, disease activity and organ involvement in systemic lupus erythematosus (SLE) patients. Patients and methods: We studied 200 SLE patients and 50 controls. We analyzed organ involvement, disease activity, serum IL-10 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. Results: Serum IL-10 and IL-6 levels were higher in SLE patients than in controls (all p < 0.00001). Serum IL-10 levels were positively correlated with IL-6 (p < 0.00001), CRP (p < 0.00001), fibrinogen (p = 0.003), and ESR (p < 0.00001), and negatively correlated with hemoglobin (p = 0.0004) and lymphocytes (p = 0.01). Serum IL-6 levels were positively correlated with CRP (p < 0.00001), fibrinogen (p = 0.001), and ESR (p < 0.00001); and negatively correlated with hemoglobin (p = 0.008) and lymphocytes (p = 0.03). Elevated serum IL-10 levels were associated with an increased risk of anti-SS-A/Ro antibody positivity (p = 0.03). Elevated serum IL-6 levels were associated with an increased risk of heart (p = 0.007) and lung (p = 0.04) involvement. Conclusions: In SLE patients, increased serum IL-10 levels were associated with increased disease activity and risk of anti–SS-A/Ro antibody positivity. Full article
(This article belongs to the Special Issue Biomarkers in Systemic Lupus Erythematosus)
13 pages, 1475 KiB  
Article
Role of Altered Metabolism of Triglyceride-Rich Lipoprotein Particles in the Development of Vascular Dysfunction in Systemic Lupus Erythematosus
by Ágnes Diószegi, Hajnalka Lőrincz, Eszter Kaáli, Pál Soltész, Bianka Perge, Éva Varga, Mariann Harangi and Tünde Tarr
Biomolecules 2023, 13(3), 401; https://doi.org/10.3390/biom13030401 - 21 Feb 2023
Cited by 6 | Viewed by 2099
Abstract
Background: Impaired lipid metabolism contributes to accelerated inflammatory responses in addition to promoting the formation of atherosclerosis in systemic lupus erythematosus (SLE). We aimed to evaluate the lipid profile, inflammatory markers, and vascular diagnostic tests in active SLE patients to clarify the association [...] Read more.
Background: Impaired lipid metabolism contributes to accelerated inflammatory responses in addition to promoting the formation of atherosclerosis in systemic lupus erythematosus (SLE). We aimed to evaluate the lipid profile, inflammatory markers, and vascular diagnostic tests in active SLE patients to clarify the association between dyslipidemia and early vascular damage. Patients and Methods: 51 clinically active SLE patients and 41 age- and gender-matched control subjects were enrolled in the study. Lipoprotein subfractions were detected by Lipoprint. Brachial artery flow-mediated dilation and common carotid intima-media thickness were detected by ultrasonography. Arterial stiffness indicated by augmentation index (Aix) and pulse wave velocity was measured by arteriography. Results: We found significantly higher Aix, higher VLDL ratio, plasma triglyceride, ApoB100, and small HDL, as well as lower HDL-C, large HDL, and ApoA1 in patients with SLE. There was a significant positive correlation of Aix with triglyceride, VLDL, IDL-C, IDL-B, and LDL1. A backward stepwise multiple regression analysis showed IDL-C subfraction to be the best predictor of Aix. Conclusions: Our results indicate that in young patients with SLE, triglyceride-rich lipoproteins influence vascular function detected by Aix. These parameters may be assessed and integrated into the management plan for screening cardiovascular risk in patients with SLE. Full article
(This article belongs to the Special Issue Biomarkers in Systemic Lupus Erythematosus)
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Review

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10 pages, 1001 KiB  
Review
Immune Phenotype as a Biomarker for Systemic Lupus Erythematosus
by Shingo Nakayamada and Yoshiya Tanaka
Biomolecules 2023, 13(6), 960; https://doi.org/10.3390/biom13060960 - 8 Jun 2023
Cited by 3 | Viewed by 1948
Abstract
The treatment of rheumatoid arthritis was revolutionized with the use of molecular-targeted drugs that target immunoregulatory molecules. The success of treatment with these drugs prompted the development of molecular-targeted drugs for systemic lupus erythematosus. However, systemic lupus erythematosus is a disease with high [...] Read more.
The treatment of rheumatoid arthritis was revolutionized with the use of molecular-targeted drugs that target immunoregulatory molecules. The success of treatment with these drugs prompted the development of molecular-targeted drugs for systemic lupus erythematosus. However, systemic lupus erythematosus is a disease with high heterogeneous immune abnormalities, and diverse cells or molecules can be treatment targets. Thus, the identification of subpopulations based on immune abnormalities is essential for the development of effective treatment. One analytical method used to identify subpopulations is the immunophenotyping of peripheral blood samples of patients. This analysis evaluates the validity of target molecules for peripheral blood immune cell subsets, which are expected to be developed as biomarkers for precision medicine in which appropriate treatment targets are set for each subpopulation. Full article
(This article belongs to the Special Issue Biomarkers in Systemic Lupus Erythematosus)
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12 pages, 302 KiB  
Review
An Antiphospholipid Antibody Profile as a Biomarker for Thrombophilia in Systemic Lupus Erythematosus
by Ryo Hisada and Tatsuya Atsumi
Biomolecules 2023, 13(4), 617; https://doi.org/10.3390/biom13040617 - 30 Mar 2023
Cited by 1 | Viewed by 2380
Abstract
Despite recent advances in treatment and significant improvements in prognosis, thrombosis remains the major cause of death in systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are the main triggers of thrombosis in patients with SLE, with a frequency of approximately 30–40%. Lupus anticoagulant, [...] Read more.
Despite recent advances in treatment and significant improvements in prognosis, thrombosis remains the major cause of death in systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are the main triggers of thrombosis in patients with SLE, with a frequency of approximately 30–40%. Lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies, which are included in the criteria for antiphospholipid syndrome, and ‘non-criteria’ aPL such as anti-phosphatidylserine/prothrombin complex antibodies, are risk factors for thrombosis in patients with SLE. Multiple positivity for aPL is also associated with an increased risk of thrombosis, and scores calculated from aPL profiles can predict the risk of developing thrombosis. Although there is insufficient evidence for treatment, aPL-positive SLE patients should/may be treated with anticoagulants and/or low-dose aspirin as appropriate. This review summarises the evidence on the clinical significance of the aPL profile as a biomarker of thrombophilia in patients with SLE. Full article
(This article belongs to the Special Issue Biomarkers in Systemic Lupus Erythematosus)
11 pages, 1172 KiB  
Review
Functional Genome Analysis for Immune Cells Provides Clues for Stratification of Systemic Lupus Erythematosus
by Keishi Fujio
Biomolecules 2023, 13(4), 591; https://doi.org/10.3390/biom13040591 - 25 Mar 2023
Cited by 3 | Viewed by 2176
Abstract
Systemic lupus erythematosus (SLE) is caused by a combination of genetic and environmental factors. Recently, analysis of a functional genome database of genetic polymorphisms and transcriptomic data from various immune cell subsets revealed the importance of the oxidative phosphorylation (OXPHOS) pathway in the [...] Read more.
Systemic lupus erythematosus (SLE) is caused by a combination of genetic and environmental factors. Recently, analysis of a functional genome database of genetic polymorphisms and transcriptomic data from various immune cell subsets revealed the importance of the oxidative phosphorylation (OXPHOS) pathway in the pathogenesis of SLE. In particular, activation of the OXPHOS pathway is persistent in inactive SLE, and this activation is associated with organ damage. The finding that hydroxychloroquine (HCQ), which improves the prognosis of SLE, targets toll-like receptor (TLR) signaling upstream of OXPHOS suggests the clinical importance of this pathway. IRF5 and SLC15A4, which are regulated by polymorphisms associated with SLE susceptibility, are functionally associated with OXPHOS as well as blood interferon activity and metabolome. Future analyses of OXPHOS-associated disease-susceptibility polymorphisms, gene expression, and protein function may be useful for risk stratification of SLE. Full article
(This article belongs to the Special Issue Biomarkers in Systemic Lupus Erythematosus)
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14 pages, 541 KiB  
Review
Complement as a Biomarker for Systemic Lupus Erythematosus
by Masahiro Ayano and Takahiko Horiuchi
Biomolecules 2023, 13(2), 367; https://doi.org/10.3390/biom13020367 - 15 Feb 2023
Cited by 12 | Viewed by 6325
Abstract
Systemic lupus erythematosus (SLE) is a disease of immune complex deposition; therefore, complement plays a vital role in the pathogenesis of SLE. In general, complement levels in blood and complement deposition in histological tests are used for the management of SLE. Thus, the [...] Read more.
Systemic lupus erythematosus (SLE) is a disease of immune complex deposition; therefore, complement plays a vital role in the pathogenesis of SLE. In general, complement levels in blood and complement deposition in histological tests are used for the management of SLE. Thus, the evaluation of complement status can be useful in the diagnosis of SLE, assessment of disease activity, and prediction of treatment response and prognosis. In addition, novel complement biomarkers, such as split products and cell-bound complement activation products, are considered to be more sensitive than traditional complement markers, such as serum C3 and C4 levels and total complement activity (CH50), which become more widely used. In this review, we report the complement testing in the management of SLE over the last decade and summarize their utility. Full article
(This article belongs to the Special Issue Biomarkers in Systemic Lupus Erythematosus)
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