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Autoimmune Diseases: From Pathogenesis to Treatment and Prognostic Markers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 February 2026 | Viewed by 4320

Special Issue Editor


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Guest Editor
Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Firenze, 50134 Firenze, Italy
Interests: autoimmune diseases; vasculitis; oxidative stress; biochemistry and pathogenesis; clinical trials; pharmacology

Special Issue Information

Dear Colleagues,

This Special Issue aims to gather new insights into the pathogenesis, diagnosis, monitoring, and treatment of autoimmune diseases. Autoimmune diseases include a wide spectrum of rare and non-rare disorders, characterized by an altered immune response involving virtually any organ and system.

The pathogenesis of autoimmune diseases is multifactorial, and includes genetic, epigenetic, environmental, infective, and immunological factors.

Autoantibodies are critical in the pathogenetic process, and can serve as valuable markers for the diagnosis, classification, and monitoring of disease activity. Autoantibodies can be detected years before the clinical onset of disease, providing a window for early diagnosis and preventive approaches. Concomitantly, other immune cell subtypes (such as T cells, neutrophils, etc.) play key parts in the pathogenesis of autoimmune disorders, although their assessment as diagnostic and prognostic biomarkers is usually more challenging.

Greater knowledge about the molecular mechanisms underlying autoimmunity may help to set up preventive strategies and targeted therapeutic approaches.

This Special Issue welcomes articles addressing, but not limited to, the following themes:

  • Genetic, epigenetic, and environmental factors underlying autoimmune diseases, including the role of the microbiome;
  • Dynamics of immune cell subsets in the pathogenesis of autoimmune diseases;
  • The role of autoantibodies and alternative biomarkers in the diagnosis, monitoring, and prognosis of autoimmune diseases;
  • Preventive approaches for autoimmune diseases;
  • Novel and selective therapeutic strategies for the treatment of autoimmune diseases.

This Special Issue accepts original research articles, clinical trials, reviews, systematic reviews and meta-analyses, case reports, and case series.

Dr. Alessandra Bettiol
Guest Editor

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Keywords

  • autoimmune diseases
  • inflammation
  • immunity
  • pathogenesis
  • immunosuppressants
  • biologics
  • biomarkers

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Published Papers (5 papers)

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Research

18 pages, 763 KB  
Article
Relationship Between High Serum Levels of Follistatin with Impaired Physical Function, and Severe Disease Activity in Rheumatoid Arthritis
by Fabiola Gonzalez-Ponce, Jorge Ivan Gamez-Nava, Heriberto Jacobo-Cuevas, Juan Manuel Ponce-Guarneros, Edgar Ricardo Valdivia-Tangarife, Cesar Arturo Nava-Valdivia, Norma Alejandra Rodriguez-Jimenez, Melissa Ramirez-Villafaña, Eli Efrain Gomez-Ramirez, Sergio Antonio Gonzalez-Vazquez, Aniel Jessica Leticia Brambila-Tapia, Eva Maria Olivas-Flores, Sylvia Totsuka-Sutto, Ernesto German Cardona-Muñoz and Laura Gonzalez-Lopez
Int. J. Mol. Sci. 2025, 26(17), 8232; https://doi.org/10.3390/ijms26178232 - 25 Aug 2025
Viewed by 554
Abstract
Rheumatoid arthritis (RA) is a highly prevalent chronic inflammatory rheumatic disorder leading to functional impairment and sequels. The search for new biomarkers helping in detecting RA subjects of high risk of functional disability is required. Studies showing high follistatin levels in RA have [...] Read more.
Rheumatoid arthritis (RA) is a highly prevalent chronic inflammatory rheumatic disorder leading to functional impairment and sequels. The search for new biomarkers helping in detecting RA subjects of high risk of functional disability is required. Studies showing high follistatin levels in RA have been described; however, none of them have placed focus on the role of follistatin as marker of deteriorated functionality. We aim to identify whether follistatin concentrations could be a potential biomarker of physical disability and disease activity in RA patients. Fifty-seven female RA subjects and 20 age–gender-matched controls were included in a cross-sectional evaluation. An assessment of clinical characteristics, grip strength, gait speed, and muscle mass was conducted. In RA subjects, disability was assessed using HAQ-DI and active disease using the DAS28-ESR. Follistatin levels were measured by ELISA. We compared (a) RA + functional disability and (b) RA + preserved physical function. Serum follistatin levels were increased in RA subjects compared to controls (175 ± 119 vs. 133 ± 47; p = 0.030). Follistatin levels correlated with deteriorated physical function levels (r = 0.491; p < 0.001) and severe activity (r = 0.344; p = 0.009). The RA + functional disability group, as compared to the RA + preserved physical function group, had higher serum follistatin levels (218 ± 159 vs. 141 ± 59; p = 0.030), lower grip strength (7.9 ± 4.6 vs. 14.5 ± 5.1; p < 0.001), reduced gait speed (0.77 ± 0.20 vs. 0.92 ± 0.20; p = 0.010), as well as higher proportions of tender joints ≥4 (48% vs. 16%; p = 0.008), and higher disease activity scores (3.8 ± 1.5 vs. 2.8 ± 1.2; p = 0.008). We concluded that higher follistatin levels are associated with physical functional impairment and the severity of disease activity in women with RA. Future studies are required to evaluate whether these follistatin levels can be related to other outcomes such as labor disability, hospitalization, and falls. Full article
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9 pages, 1209 KB  
Communication
Clinical, Immunological, Radiographic, and Pathologic Improvements in a Patient with Long-Standing Crohn’s Disease After Receiving Stem Cell Educator Therapy
by Richard Fox, Boris Veysman, Kristine Antolijao, Noelle Mendoza, Ruby Anne Lorenzo, Honglan Wang, Zhi Hua Huang, Yelu Zhao, Yewen Zhao, Terri Tibbot, Darinka Povrzenic, Mary Lauren Bayawa, Sophia Kung, Bassam Saffouri and Yong Zhao
Int. J. Mol. Sci. 2025, 26(15), 7292; https://doi.org/10.3390/ijms26157292 - 28 Jul 2025
Viewed by 597
Abstract
Crohn’s disease is a chronic inflammation affecting the gastrointestinal tract. To date, patients are commonly treated with corticosteroids or more aggressive biologics for high-risk subjects. Stem Cell Educator therapy has been successfully utilized to treat patients with type 1 diabetes and other autoimmune [...] Read more.
Crohn’s disease is a chronic inflammation affecting the gastrointestinal tract. To date, patients are commonly treated with corticosteroids or more aggressive biologics for high-risk subjects. Stem Cell Educator therapy has been successfully utilized to treat patients with type 1 diabetes and other autoimmune conditions. A 78-year-old patient with long-standing Crohn’s disease received one treatment with the Stem Cell Educator therapy, followed by clinical, radiographic, pathological examinations and immune marker testing by flow cytometry. After the treatment with Stem Cell Educator therapy, the patient’s clinical symptoms were quickly improved with normal bowel movements, without abdominal pain or rectal bleeding. Flow cytometry analysis revealed a marked decline in inflammatory markers, such as the percentage of monocyte/macrophage-associated cytokine interleukin-1 beta (IL-1β)+ cells, which reduced from 94.98% at the baseline to 18.21%, and down-regulation of the percentage of chemokine CXCL16+ cells from 91.92% at baseline to 42.58% at 2-month follow-up. Pathologic examination of the biopsy specimens from colonoscopy five weeks and six months post-treatment showed ileal mucosa with no specific abnormality and no significant inflammation or villous atrophy; no granulomas were identified. A follow-up CT scan four and one-half months post-treatment showed no evidence of the previously seen stenosis of the ilio-colonic anastomosis with proximal dilatation. Stem Cell Educator therapy markedly reduced inflammation in the subject with Crohn’s disease, leading to durable clinical, immunological, radiographic, and pathological improvements. Full article
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17 pages, 3492 KB  
Article
Similarity to Self-Antigens Shapes Epitope Recognition from Viruses Under Autoimmune and Infectious Disease
by Alvaro Ras-Carmona, Alexander Lehmann and Pedro A. Reche
Int. J. Mol. Sci. 2025, 26(13), 6041; https://doi.org/10.3390/ijms26136041 - 24 Jun 2025
Viewed by 597
Abstract
Self/non-self-discrimination is a fundamental aspect of adaptive immunity, which helps prevent harmful autoimmune responses. However, infectious agents can also act as environmental catalysts for autoimmune diseases. In this study, we investigated the role of molecular mimicry to self-antigens in epitope recognition in relation [...] Read more.
Self/non-self-discrimination is a fundamental aspect of adaptive immunity, which helps prevent harmful autoimmune responses. However, infectious agents can also act as environmental catalysts for autoimmune diseases. In this study, we investigated the role of molecular mimicry to self-antigens in epitope recognition in relation to infectious and autoimmune diseases. To this end, we performed BLAST searches against the human proteome, utilizing known virus-specific B and T cell peptide epitopes identified in association with autoimmune or infectious diseases in humans as our queries. Additionally, similar control analyses were carried out using non-B and non-T cell epitopes, consisting of random viral peptide sequences. Overall, our results endorsed a major role of molecular mimicry in instigating or sustaining autoimmunity associated with viral infections and challenged the prevailing view on self/non-self-discrimination for T cells. Additionally, we uncovered many virus-specific epitopes among those identified in association with infectious diseases with high similarity to self-antigens, which are primarily derived from human coronaviruses and various flaviviruses. Recognition of these epitopes could lead to autoimmunity against human proteins that are in cellular components concerning cell motility, cell membrane projections, and cellular synapses. Full article
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27 pages, 5833 KB  
Article
Investigating the Role of Gut Microbiota in the Pathogenesis and Progression of Rheumatoid Arthritis in a Collagen-Induced Arthritis Mouse Model
by Paulína Belvončíková, Kristína Macáková, Nikola Tóthová, Pavel Babál, Lenka Tarabčáková and Roman Gardlík
Int. J. Mol. Sci. 2025, 26(11), 5099; https://doi.org/10.3390/ijms26115099 - 26 May 2025
Viewed by 929
Abstract
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder whose precise etiology remains unclear, though growing evidence implicates gut microbiota in its pathogenesis. This study aimed to investigate the role of gut microbiota in the onset and progression of RA by employing fecal [...] Read more.
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder whose precise etiology remains unclear, though growing evidence implicates gut microbiota in its pathogenesis. This study aimed to investigate the role of gut microbiota in the onset and progression of RA by employing fecal microbiota transplantation (FMT) in a collagen-induced arthritis (CIA) mouse model using DBA/1J and Aire/ strains. Mice received FMT from healthy donors, treatment-naïve RA patients, or treated RA patients in relapse, followed by assessment of microbiota composition via 16S rRNA sequencing, arthritis severity scoring, histological evaluations, and systemic inflammatory markers. The findings revealed distinct microbiota clustering patterns post-FMT across experimental groups, highlighting strain-specific colonization effects. Notably, genera such as Bifidobacterium and Paraprevotella correlated positively with arthritis severity in DBA/1J mice, whereas Corynebacterium, Enterorhabdus, and Odoribacter exhibited negative correlations, suggesting potential protective roles. Despite these microbial differences, minor variations in arthritis scores, paw inflammation, or systemic inflammation were observed among FMT groups. This indicates that although gut microbiota alterations are associated with RA pathogenesis, further investigation with larger cohorts and comprehensive sequencing approaches is essential to elucidate the therapeutic potential of microbiome modulation in autoimmune diseases. Full article
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18 pages, 2496 KB  
Article
IgA Antibodies to Bovine Serum Albumin in Adult Patients with Celiac Disease
by Elena Savvateeva, Marina Yukina, Nurana Nuralieva, Svetlana Bykova, Ivan Abramov, Vera Polyakova, Natalia Bodunova, Maxim Donnikov, Lyudmila Kovalenko, Elena Mazurenko, Elizaveta Pavlova, Elena Kulagina, Ekaterina Troshina and Dmitry Gryadunov
Int. J. Mol. Sci. 2025, 26(11), 4988; https://doi.org/10.3390/ijms26114988 - 22 May 2025
Viewed by 1014
Abstract
This study investigated the IgA antibodies targeting bovine serum albumin (BSA) in 27 adult celiac disease (CD) patients adhering to a gluten-free diet (GFD), compared to 123 controls (including individuals with autoimmune disorders, those with gastrointestinal cancers, and healthy donors). Serum samples were [...] Read more.
This study investigated the IgA antibodies targeting bovine serum albumin (BSA) in 27 adult celiac disease (CD) patients adhering to a gluten-free diet (GFD), compared to 123 controls (including individuals with autoimmune disorders, those with gastrointestinal cancers, and healthy donors). Serum samples were evaluated using a multiplex assay based on a microarray comprising 66 immobilized antigens, including autoantigens associated with autoimmune diseases, different albumins, cytokines, and inflammatory markers. Elevated IgA-BSA levels were detected in 22% of CD patients versus 3.25% of controls. IgA-BSA did not cross-react with milk proteins like casein, β-lactoglobulin, and γ-globulin, nor with autoantigens and human albumin, ruling out autoimmunity against self-proteins. The observed cross-reactivity with porcine albumin suggests that antibodies target epitopes shared by bovine and porcine albumin. Increased IgA-BSA levels may interfere with immunoassays performed using BSA as a stabilizer, necessitating protein-free buffers to avoid false results when testing CD patients. Elevated IgA-BSA levels may reflect ongoing gut barrier dysfunction in CD patients on a GFD, allowing dietary proteins like BSA to trigger immune responses. This study identifies a novel immune response in CD patients on a GFD, emphasizing the need for tailored diagnostic approaches (BSA-free assays) and further research into the clinical and dietary implications of IgA-BSA elevation. Full article
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