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Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 14828

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Special Issue Editor

Dr. Sasa Cucnik

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Guest Editor

1. Department of Rheumatology, University Medical Centre Ljubljana, University of Ljubljana, 1000 Ljubljana, Slovenia
2. Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
Interests: autoimmunity; autoantibodies; systemic autoimmune diseases

Special Issue Information

Dear Colleagues,

The Special Issue, “Autoimmune Diseases Mechanisms and Novel Therapeutic Approaches”, will focus on the pathophysiological mechanisms, clinical manifestations, and novel therapeutic approaches of systemic and organ specific autoimmune diseases.

The immune system has evolved to protect the host from microbial infection, but the breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Autoimmune diseases are multifactorial diseases, meaning that genetic, environmental, hormonal, and immunological factors are all considered important in their development. Autoimmune diseases are a range of a complex and clinically heterogeneous autoimmune diseases with a wide spectrum of different clinical manifestations and dysregulated innate and adaptive immune response leading in tissue dysfunction. For most autoimmune diseases, there is also a clear sex difference in prevalence, and females are, generally, more frequently affected than males.

A clearer understanding of the mechanisms driving disease pathogenesis enable a better understanding of the disease, better stratification of patients, and better progress in personalized approach of treatment by discovery of new target therapeutic options. This Special Issue is, therefore, open for both clinical and basic research and will cover original articles, as well as reviews concerning pathophysiology and molecular mechanisms of organ specific and systemic autoimmune diseases, clinical features of organ specific and systemic autoimmune diseases and traditional and innovative therapeutic approaches for autoimmune diseases.

Dr. Sasa Cucnik
Guest Editor

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Keywords

organ specific autoimmune diseases
systemic autoimmune diseases
pathophysiology
molecular mechanisms
novel therapeutic approaches

Published Papers (10 papers)

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Research

Jump to: Review

12 pages, 2148 KiB

Open AccessArticle

Anifrolumab for Moderate and Severe Muco-Cutaneous Lupus Erythematosus: A Monocentric Experience and Review of the Current Literature

by Giovanni Paolino, Giuseppe A. Ramirez, Chiara Calabrese, Luca Moroni, Vittoria Giulia Bianchi, Enrica P. Bozzolo, Santo Raffaele Mercuri and Lorenzo Dagna

Biomedicines 2023, 11(11), 2904; https://doi.org/10.3390/biomedicines11112904 - 26 Oct 2023

Viewed by 1176

Abstract

Refractory cutaneous manifestations constitute a significant unmet need in patients with cutaneous lupus (CLE), even in the setting of systemic lupus erythematosus (SLE) with otherwise good control of inflammatory manifestations. Anifrolumab, an anti-interferon I receptor monoclonal antibody has recently been approved for serologically positive SLE with or without CLE, but real-life efficacy and safety data are currently limited. In addition, relatively limited evidence exists about the spectrum of cutaneous manifestations potentially benefitting from anifrolumab treatment and about the optimal clinimetrics to monitor treatment efficacy. While summarising current evidence on the topic in the literature, we report on four patients with SLE and refractory CLE who were successfully treated with anifrolumab. We also describe the potential usefulness and complementarity of the cutaneous lupus activity investigator’s global assessment (CLA-IGA) in assessing cutaneous activity in patients treated with anifrolumab. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

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16 pages, 2179 KiB

Open AccessArticle

Disturbed Antioxidant Capacity in Patients with Systemic Sclerosis Associates with Lung and Gastrointestinal Symptoms

by Neža Brezovec, Katja Perdan-Pirkmajer, Blaž Burja, Žiga Rotar, Joško Osredkar, Snežna Sodin-Šemrl, Katja Lakota and Saša Čučnik

Biomedicines 2023, 11(8), 2110; https://doi.org/10.3390/biomedicines11082110 - 26 Jul 2023

Viewed by 726

Abstract

The correct balance between reactive oxygen species and antioxidant defense in an organism is disturbed in oxidative stress. To assess oxidative balance in 36 SSc patients and 26 healthy controls (HCs), we measured reactive oxidative metabolites (ROMs), total antioxidant capacity (TAC), lipid peroxidation (measuring 4-HNE), and DNA oxidative damage (measuring 8-OHdG) in serum. Furthermore, DNA breaks in leukocytes of 35 SSc patients and 32 HCs were evaluated using COMET. While we report high ROMs for both SSc patients and age/sex matched HC samples, there was a significant increase in TAC in SSc patients as compared to HCs, and thus also a significantly higher oxidative stress index in SSc patients. TAC was significantly higher in SSc patients with ILD and gastrointestinal involvement, as well as in patients with anti-topoisomerase antibodies. We observe no difference in serum lipid peroxidation status or oxidative DNA damage. However, SSc patients had significantly more leukocyte DNA breaks than HCs; the most damage was observed in patients treated with immunosuppressives. Thus, our study confirms presence of oxidative stress and increased DNA damage in leukocytes of SSc patients; however, it points toward increased antioxidant capacity, which needs to be further studied. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

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9 pages, 874 KiB

Open AccessArticle

Anti-Cytosolic 5′-Nucleotidase 1A in the Diagnosis of Patients with Suspected Idiopathic Inflammatory Myopathies: An Italian Real-Life, Single-Centre Retrospective Study

by Brunetta Porcelli, Miriana d’Alessandro, Latika Gupta, Silvia Grazzini, Nila Volpi, Maria Romana Bacarelli, Federica Ginanneschi, Giovanni Biasi, Francesca Bellisai, Marta Fabbroni, David Bennett, Claudia Fabiani, Luca Cantarini, Elena Bargagli, Bruno Frediani and Edoardo Conticini

Biomedicines 2023, 11(7), 1963; https://doi.org/10.3390/biomedicines11071963 - 12 Jul 2023

Cited by 1 | Viewed by 1169

Abstract

Background: Anti-cytosolic 5′-nucleotidase 1A (anti-cN1A) antibodies were proposed as a biomarker for the diagnosis of inclusion body myositis (IBM), but conflicting specificity and sensitivity evidence limits its use. Our study aimed to assess the diagnostic accuracy of anti-cN1A in a cohort of patients who underwent a myositis line immunoassay for suspected idiopathic inflammatory myopathies (IIM). We also assessed the agreement between two testing procedures: line immunoassay (LIA) and enzyme-linked immunoassay (ELISA). Materials and methods: We collected retrospective clinical and serological data for 340 patients who underwent a myositis antibody assay using LIA (EUROLINE Autoimmune Inflammatory Myopathies 16 Ag et cN-1A (IgG) line immunoassay) and verification with an anti-cN1A antibody assay using ELISA (IgG) (Euroimmun Lubeck, Germany). Results: The serum samples of 20 (5.88%) patients (15 females, 5 males, mean age 58.76 ± 18.31) tested positive for anti-cN1A using LIA, but only two out of twenty were diagnosed with IBM. Seventeen out of twenty tested positive for anti-cN1A using ELISA (median IQR, 2.9 (1.9–4.18)). Conclusions: Our study suggests excellent concordance between LIA and ELISA for detecting anti-cN1A antibodies. LIA may be a rapid and useful adjunct, and it could even replace ELISA for cN1A assay. However, the high prevalence of diseases other than IBM in our cohort of anti-cN1A-positive patients did not allow us to consider anti-cN1A antibodies as a specific biomarker for IBM. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

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11 pages, 1584 KiB

Open AccessArticle

New Onset Autoimmune Diseases after the Sputnik Vaccine

by Olga Vera-Lastra, Gabriela Mora, Abihai Lucas-Hernández, Alberto Ordinola-Navarro, Emmanuel Rodríguez-Chávez, Ana Lilia Peralta-Amaro, Gabriela Medina, María Pilar Cruz-Dominguez, Luis J. Jara and Yehuda Shoenfeld

Biomedicines 2023, 11(7), 1898; https://doi.org/10.3390/biomedicines11071898 - 04 Jul 2023

Viewed by 2159

Abstract

The vertiginous advance for identifying the genomic sequence of SARS-CoV-2 allowed the development of a vaccine including mRNA-based vaccines, inactivated viruses, protein subunits, and adenoviral vaccines such as Sputnik. This study aims to report on autoimmune disease manifestations that occurred following COVID-19 Sputnik vaccination. Patients and Methods: A retrospective study was conducted on patients with new-onset autoimmune diseases induced by a post-COVID-19 vaccine between March 2021 and December 2022, in two referral hospitals in Mexico City and Argentina. The study evaluated patients who received the Sputnik vaccine and developed recent-onset autoimmune diseases. Results: Twenty-eight patients developed recent-onset autoimmune diseases after Sputnik vaccine. The median age was 56.9 ± 21.7 years, with 14 females and 14 males. The autoimmune diseases observed were neurological in 13 patients (46%), hematological autoimmune manifestations occurred in 12 patients (42%), with thrombotic disease observed in 10 patients (28%), and autoimmune hemolytic anemia in two patients (7.1%). Rheumatological disorders were present in two patients (7.1%), and endocrine disorders in one patient (3.5%). Principio del formulario Conclusion: Although the COVID-19 Sputnik vaccine is generally safe, it can lead to adverse effects. Thrombosis and Guillain-Barre were the most frequent manifestations observed in our group of patients. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

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11 pages, 3957 KiB

Open AccessArticle

Real-World Endoscopic and Histologic Outcomes in Ulcerative Colitis Patients: A Retrospective Cohort Study

by Monica State, Paul Balanescu, Theodor Voiosu, Andreea Bengus, Andrei Voiosu, Andrei Coman, Petronel Mustatea, Lucian Negreanu, Radu Bogdan Mateescu and Cristiana Popp

Biomedicines 2023, 11(7), 1860; https://doi.org/10.3390/biomedicines11071860 - 29 Jun 2023

Viewed by 845

Abstract

Background: Histologic activity has emerged as an aspirational therapeutic goal in ulcerative colitis management. It is not yet a formal treatment target in ulcerative colitis. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. We investigated mucosal and histologic remission rates and potential predictors of these outcomes in a cohort of UC patients. Methods: We conducted a retrospective analysis of data collected from UC patients enrolled in an ongoing prospective cohort study. Mucosal healing was defined as Mayo endoscopic score = 0. Results: A total of 131 patients with ulcerative colitis were enrolled in our study and were prospectively followed for a median length of 2 years (range 0–5 years), totaling 266 study visits. Mucosal healing was recorded for 27 patients at 70 (26%) different study visits. For patients with mucosal healing, histologic remission was achieved in 18/27 (66%) patients. On univariate analysis, sustained clinical remission, SIBDQ scores ≥ 5.5, CRP ≤ 5 mg/dL and absence of corticotherapy were associated with mucosal healing and SIBDQ scores ≥ 5.5 and CRP ≤ 5 mg/dL with histologic healing, respectively. After logistic regression analysis, none of the investigated factors were associated with mucosal and histologic healing. The number of CD8+ intraepithelial lymphocytes (IELs) was significantly greater than the number of CD4+ IELs in periods of disease activity, as well as during mucosal healing (p < 0.01 in both cases). Conclusions: Mucosal healing and histologic remission rates are low in real-life settings. The results of univariate analysis indicate that a good quality of life (SIBDQ score) and normal inflammatory markers (CRP) are associated with mucosal and histologic healing. However, frequently used patient- and disease-related factors, including mucosal healing, are not reliable predictors for histologic remission. Greater CD8+ lymphocyte involvement and higher CD8+/CD4+ distribution can have a meaningful impact on understanding the pathogenesis and natural history of ulcerative colitis, as well as future treatment options for lymphocyte-targeting medications. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

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10 pages, 281 KiB

Open AccessArticle

Changes in Clinical Manifestations and Course of Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome over Three Decades

by Nikolett Nagy, Gábor Papp, Eszter Gáspár-Kiss, Ágnes Diószegi and Tünde Tarr

Biomedicines 2023, 11(4), 1218; https://doi.org/10.3390/biomedicines11041218 - 19 Apr 2023

Cited by 2 | Viewed by 1563

Abstract

Systemic lupus erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which potentially results in a more severe disease course and reduced life expectancy. Since the therapeutic guidelines have been refined in the last 15 years, we assumed that the diseases course has become more favorable. In order to shed light on these achievements, we compared the data of SLE patients diagnosed before and since 2004. In our retrospective study, we assessed a wide spectrum of clinical and laboratory data of 554 SLE patients who received regular follow-up care and therapy at our autoimmune center. Among these patients, 247 had antiphospholipid antibodies (APAs) without clinical signs of APS, and 113 had definitive APS. In the APS group, among patients diagnosed since 2004, deep vein thrombosis (p = 0.049) and lupus anticoagulant positivity (p = 0.045) were more frequent, while acute myocardial infarction was less frequent (p = 0.021) compared with patients diagnosed before 2004. Among the APA positive patients without definitive APS, anti-cardiolipin antibody positivity (p = 0.024) and development of chronic renal failure (p = 0.005) decreased in patients diagnosed since 2004. Our study demonstrates that the disease course has changed in recent years; however, in the presence of APS, we have to expect repeated thrombotic events despite adequate anticoagulant therapy. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

13 pages, 9368 KiB

Open AccessArticle

Intramuscular Polydeoxyribonucleotides in Fibrotic and Atrophic Localized Scleroderma: An Explorative Prospective Cohort Study

by Maurizio Romagnuolo, Chiara Moltrasio, Angelo Valerio Marzano, Gianluca Nazzaro, Simona Muratori and Sebastiano Recalcati

Biomedicines 2023, 11(4), 1190; https://doi.org/10.3390/biomedicines11041190 - 17 Apr 2023

Viewed by 1045

Abstract

Effective options in the quiescent, scantily inflammatory phase of localized scleroderma (morphea) are lacking. A cohort study in patients with histologically confirmed fibroatrophic morphea explored the therapeutic value of the anti-dystrophic A2A adenosine agonist polydeoxyribonucleotide (PDRN, one daily 5.625 mg/3 mL ampoule for 90 days with a three-month follow-up). Primary efficacy endpoints: Localized Scleroderma Cutaneous Assessment Tool mLoSSI and mLoSDI subscores for disease activity and damage in eighteen areas; Physicians Global Assessment for Activity (PGA-A) and Damage (PGA-D) VAS scores; skin echography. Secondary efficacy endpoints: mLoSSI, mLoSDI, PGA-A, PGA-D, and morphea areas (photographs) over time; Dermatology Life Quality Index (DLQI); skin biopsy scores and induration over time. Twenty-five patients enrolled; 20 completed the follow-up period. Highly significant improvements at the end of the 3-month treatment period: mLoSSI–73.7%, mLoSDI–43.9%, PGA-A–60.4%, PGA-D–40.3%, with further improvements at follow-up visit for all disease activity and damage indexes. Overall, the outcomes suggest that a daily PDRN ampoule intramuscularly for 90 days reduces disease activity and damage rapidly and significantly in quiescent, modestly inflammatory morphea with few currently therapeutic options. The COVID-19 pandemic and lockdowns caused difficulties in enrollment, and some patients were lost to follow-up. Due to low final enrollment, the study outcomes may have only an exploratory value, yet they appear impressive. The anti-dystrophic potential of the PDRN A2A adenosine agonist deserves further in-depth exploration. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

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16 pages, 5147 KiB

Open AccessArticle

Rapamycin Treatment Alleviates Chronic GVHD-Induced Lupus Nephritis in Mice by Recovering IL-2 Production and Regulatory T Cells While Inhibiting Effector T Cells Activation

by Jilu Zhang, Xun Wang, Renxi Wang, Guojiang Chen, Jing Wang, Jiannan Feng, Yan Li, Zuyin Yu and He Xiao

Biomedicines 2023, 11(3), 949; https://doi.org/10.3390/biomedicines11030949 - 20 Mar 2023

Viewed by 1759

Abstract

In this study, we test the therapeutic effects of rapamycin in a murine model of SLE-like experimental lupus nephritis induced by chronic graft-versus-host disease (cGVHD). Our results suggest that rapamycin treatment reduced autoantibody production, inhibited T lymphocyte and subsequent B cell activation, and reduced inflammatory cytokine and chemokine production, thereby protecting renal function and alleviating histological lupus nephritis by reducing the occurrence of albuminuria. To explore the potential mechanism of rapamycin’s reduction of kidney damage in mice with lupus nephritis, a series of functional assays were conducted. As expected, rapamycin remarkably inhibited the lymphocytes’ proliferation within the morbid mice. Interestingly, significantly increased proportions of peripheral CD4+FOXP3+ and CD4+CD25high T cells were observed in rapamycin-treated group animals, suggesting an up-regulation of regulatory T cells (Tregs) in the periphery by rapamycin treatment. Furthermore, consistent with the results regarding changes in mRNA abundance in kidney by real-time PCR analysis, intracellular cytokine staining demonstrated that rapamycin treatment remarkably diminished the secretion of Th1 and Th2 cytokines, including IFN-γ, IL-4 and IL-10, in splenocytes of the morbid mice. However, the production of IL-2 from splenocytes in rapamycin-treated mice was significantly higher than in the cells from control group animals. These findings suggest that rapamycin treatment might alleviate systemic lupus erythematosus (SLE)-like experimental lupus nephritis through the recovery of IL-2 production, which promotes the expansion of regulatory T cells while inhibiting effector T cell activation. Our studies demonstrated that, unlike other commonly used immunosuppressants, rapamycin does not appear to interfere with tolerance induction but permits the expansion and suppressive function of Tregs in vivo. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

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Review

Jump to: Research

27 pages, 1418 KiB

Open AccessReview

A Comprehensive Review on Neuroimmunology: Insights from Multiple Sclerosis to Future Therapeutic Developments

by Lucian Eva, Horia Pleș, Razvan-Adrian Covache-Busuioc, Luca Andrei Glavan, Bogdan-Gabriel Bratu, Andrei Bordeianu, David-Ioan Dumitrascu, Antonio Daniel Corlatescu and Alexandru Vlad Ciurea

Biomedicines 2023, 11(9), 2489; https://doi.org/10.3390/biomedicines11092489 - 08 Sep 2023

Cited by 3 | Viewed by 1860

Abstract

This review delves into neuroimmunology, focusing on its relevance to multiple sclerosis (MS) and potential treatment advancements. Neuroimmunology explores the intricate relationship between the immune system and the central nervous system (CNS). Understanding these mechanisms is vital for grasping the pathophysiology of diseases like MS and for devising innovative treatments. This review introduces foundational neuroimmunology concepts, emphasizing the role of immune cells, cytokines, and blood–brain barrier in CNS stability. It highlights how their dysregulation can contribute to MS and discusses genetic and environmental factors influencing MS susceptibility. Cutting-edge research methods, from omics techniques to advanced imaging, have revolutionized our understanding of MS, offering valuable diagnostic and prognostic tools. This review also touches on the intriguing gut–brain axis, examining how gut microbiota impacts neuroimmunological processes and its potential therapeutic implications. Current MS treatments, from immunomodulatory drugs to disease-modifying therapies, are discussed alongside promising experimental approaches. The potential of personalized medicine, cell-based treatments, and gene therapy in MS management is also explored. In conclusion, this review underscores neuroimmunology’s significance in MS research, suggesting that a deeper understanding could pave the way for more tailored and effective treatments for MS and similar conditions. Continued research and collaboration in neuroimmunology are essential for enhancing patient outcomes. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

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12 pages, 1902 KiB

Open AccessReview

Lupus Nephritis and Dysbiosis

by Marta Monticolo, Krzysztof Mucha and Bartosz Foroncewicz

Biomedicines 2023, 11(4), 1165; https://doi.org/10.3390/biomedicines11041165 - 13 Apr 2023

Cited by 2 | Viewed by 1563

Abstract

Lupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus (SLE). The risk factors for developing LN by SLE patients are not fully understood. They are considered to be a mix of genetic and environmental variables, one of them being dysbiosis, proposed recently to interfere with autoimmunity. As of yet, the relations between the human microbiome, its genetic determinants, individual variability and clinical consequences remain to be established. One of the major obstacles in studying them is the magnitude of confounders, such as diet, drugs, infections or antibiotics use. They also make comparison between the studies extremely complicated. We reviewed the available evidence for the interplay between microbiome, dysbiosis and mechanisms triggering the autoimmune responses and potentially contributing to LN development. One such mechanism is the stimulation of autoimmune responses by bacterial metabolites that can mimic autoantigens and cause antibody production. These mimicking microbial antigens seem to be a promising target for future interventions. Full article

(This article belongs to the Special Issue Autoimmune Diseases: Mechanisms and Novel Therapeutic Approaches)

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