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Medicina
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Autoimmune Diseases: Advances and Challenges
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Autoimmune Diseases: Advances and Challenges

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Hematology and Immunology".

Deadline for manuscript submissions: closed (30 April 2026) | Viewed by 12729

Special Issue Editors

Prof. Dr. Abdulla Watad

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Guest Editor
Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262100, Israel
Interests: comorbidities of ankylosing spondylitis; early diagnosis of ankylosing spondylitis; new bone formation; prevention of psoriatic arthritis; enthesitis and enthesopathy
Special Issues, Collections and Topics in MDPI journals
Dr. Kassem Sharif

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Guest Editor
Sheba Medical Center, Tel Aviv University, Tel Aviv-Yafo, Israel
Interests: asnkylosing spondylitis; spondyloarthropathies; inflammatory bowel diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Niv Ben-Shabat

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Guest Editor Assistant
1. Internal Medicine B, Sheba Medical Center, Tel-Hashomer, Ramat Gan 52621, Israel
2. Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Interests: ankylosing spondylitis; psoriatic arthritis; inflammatory bowel disease (IBD); spondyloarthropathy; inflammation; autoimmunity; dermatology; rheumatology

Special Issue Information

Dear Colleagues,

Autoimmune diseases are the result of the immune system mistakenly attacking the body's own tissues and encompass a vast spectrum of disorders. These conditions, ranging from systemic lupus erythematosus and rheumatoid arthritis to organ-specific diseases like type 1 diabetes and Hashimoto’s thyroiditis, affect millions worldwide and pose significant diagnostic, therapeutic, and research challenges.

This Special Issue, “Autoimmune Diseases: Advances and Challenges”, seeks to bring together cutting-edge research and clinical insights to enhance our understanding of autoimmune pathophysiology, explore emerging therapeutic strategies, and address unresolved controversies. We welcome submissions of original research articles, epidemiologic studies, compelling case reports, case series, and comprehensive reviews.

Key topics of interest include breakthroughs in immunomodulatory therapies, the role of environmental and genetic factors, innovative diagnostic tools, and the interplay between autoimmunity and comorbid conditions such as cardiovascular diseases and malignancies. By contributing to this issue, authors can help to shape the conversation on the future of autoimmune disease management and contribute to improving outcomes for patients.

We invite clinicians, researchers, and healthcare professionals to submit their work in order to foster collaboration and drive innovation in this vital field.

Prof. Dr. Abdulla Watad
Dr. Kassem Sharif
Guest Editors

Dr. Niv Ben-Shabat
Guest Editor Assistant

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 250 words) can be sent to the Editorial Office for assessment.

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. Medicina 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 2200 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

  • autoimmunity
  • inflammation
  • arthritis
  • psoriasis
  • metabolic syndrome
  • lupus
  • thyroiditis
  • vasculitis
  • autoinflammatory conditions

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Published Papers (6 papers)

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12 pages, 565 KB  
Article
Associations Between Composite Host Vulnerability Score and Transfusion Outcomes After Trauma
by Yun-Chul Park, Young-Goun Jo, Hyun-Seok Jang, Eui-Sung Jeong and Ji-Hyoun Kang
Medicina 2026, 62(4), 732; https://doi.org/10.3390/medicina62040732 - 12 Apr 2026
Viewed by 389
Abstract
Background and Objectives: Outcomes after trauma are traditionally attributed to injury severity and acute physiologic derangement. However, host vulnerability at presentation—reflecting underlying physiologic and nutritional status—may also be associated with bleeding severity and transfusion requirements following acute injury. Whether such vulnerability contributes [...] Read more.
Background and Objectives: Outcomes after trauma are traditionally attributed to injury severity and acute physiologic derangement. However, host vulnerability at presentation—reflecting underlying physiologic and nutritional status—may also be associated with bleeding severity and transfusion requirements following acute injury. Whether such vulnerability contributes additional risk information beyond established factors remains incompletely understood. Materials and Methods: We conducted a retrospective cohort study of adult trauma patients using a single-center trauma registry. Host vulnerability was assessed using a composite score (CE; range 0–3) based on admission hypoalbuminemia (<3.5 g/dL), anemia (hemoglobin < 11 g/dL), and reduced renal function (estimated glomerular filtration rate < 60 mL/min/1.73 m2). Primary outcomes were any blood transfusion and massive transfusion, defined as transfusion of ≥10 units of packed red blood cells within 24 h of admission. Associations between CE score and transfusion outcomes were evaluated using univariable and multivariable logistic regression models adjusted for age, Injury Severity Score (ISS), admission lactate level, and systolic blood pressure (SBP). Results: Among 4105 trauma patients, transfusion requirements increased progressively with higher CE scores. Rates of any transfusion rose from 21.7% in patients with CE 0 to 78.6% in those with CE 3, while massive transfusion increased from 1.9% to 23.1% across the same categories. In multivariable analyses, each 1-point increase in CE score was independently associated with higher odds of any transfusion (adjusted odds ratio [aOR] 3.21, 95% confidence interval [CI] 2.80–3.68) and massive transfusion (aOR 1.73, 95% CI 1.45–2.07). Conclusions: A composite score reflecting host vulnerability at presentation was associated with bleeding severity and transfusion requirements after trauma, beyond injury severity and acute physiologic factors. These findings suggest that simple laboratory-based markers may provide additional information for early risk stratification of hemorrhagic outcomes after trauma. Full article
(This article belongs to the Special Issue Autoimmune Diseases: Advances and Challenges)
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16 pages, 499 KB  
Article
Immunological Biomarkers to Assess Activity and Treatment Response in IgG4-Related Disease
by Patricia Moya-Alvarado, Marta Lopez-Gomez, Laura Martínez-Martinez, Hye Sang Park, Teresa Franco Leyva, Mar Concepción Martín, Helena Codes-Mendez, Anna Calvet Lacruz, Sara Calleja, Berta Magallares, Iván Castellví, Antonio J. Barros-Membrilla, Julia Bernárdez and Hèctor Corominas
Medicina 2026, 62(2), 323; https://doi.org/10.3390/medicina62020323 - 4 Feb 2026
Cited by 1 | Viewed by 827
Abstract
Background and Objectives: IgG4-related disease is a chronic fibro-inflammatory condition. Despite the development of classification and responder indexes, reliable biomarkers for disease activity and therapeutic monitoring remain limited. We evaluate the performance of a panel of biomarkers, including cytokine profiles, plasmablasts and [...] Read more.
Background and Objectives: IgG4-related disease is a chronic fibro-inflammatory condition. Despite the development of classification and responder indexes, reliable biomarkers for disease activity and therapeutic monitoring remain limited. We evaluate the performance of a panel of biomarkers, including cytokine profiles, plasmablasts and conventional markers. Materials and Methods: We conducted a cross-sectional, single-center study, involving 35 patients diagnosed with IgG4-RD. Disease activity was evaluated using the IgG4-RD Responder Index (RI), Damage Index (DI) and clinical assessment. Laboratory evaluation included serum IgG4, total IgG, CRP, ESR, eosinophils, IgE, complement levels, and cytokine profiling via multiplex immunoassay. B cell subpopulations were analyzed by flow cytometry. Statistical analyses were performed using STATA/BE 17.0. Results: Patients with active disease (RI > 4 or clinical judgment) exhibited significantly higher levels of total IgG (p = 0.02), IgG4 (p = 0.01), and IL-5 (p = 0.03). PET-positive patients showed a Th1-skewed immune profile, with elevated IFN-γ/IL-4 (p < 0.001), reduced IL-21/IFN-γ (p = 0.03), and increased eosinophils (p = 0.03). Clinician-assessed active disease was associated with higher total IgG levels (p = 0.01). Treatment-specific effects were observed: prednisone was associated with lower IgG4 and C3 levels. Notably, plasmablasts did not consistently correlate with clinical or imaging activity scores, possibly reflecting treatment status or B cell dynamics. Conclusions: This study demonstrates that cytokine ratios, particularly those involving IL-5, IL-13, IL-21, and IFN-γ, offer complementary information to traditional serological markers for IgG4-RD activity. While PET/CT-defined activity was best reflected by biomarkers of an IFN-γ-mediated pathway, the IgG4-RD RI demonstrated a stronger association with conventional humoral markers like serum IgG4 and total IgG. None of these biomarkers correlated with organ damage. Full article
(This article belongs to the Special Issue Autoimmune Diseases: Advances and Challenges)
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13 pages, 406 KB  
Article
Familial Versus Non-Familial Vitiligo: Clinical Features, Anatomical Distribution, and Autoimmune Comorbidity from a Southern Taiwan Hospital
by Ning-Sheng Lai, Hsiu-Hua Chang, Hui-Chin Lo, Ming-Chi Lu and Malcolm Koo
Medicina 2025, 61(11), 2040; https://doi.org/10.3390/medicina61112040 - 14 Nov 2025
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Abstract
Background and Objectives: Familial clustering and autoimmune multimorbidity are frequently observed in vitiligo. However, the clinical implications of a positive family history across generations remain unclear. In this study, a positive family history was defined as having at least one affected parent [...] Read more.
Background and Objectives: Familial clustering and autoimmune multimorbidity are frequently observed in vitiligo. However, the clinical implications of a positive family history across generations remain unclear. In this study, a positive family history was defined as having at least one affected parent or grandparent. Materials and Methods: We retrospectively reviewed the electronic medical records of 972 adults with vitiligo who attended the rheumatology division in a regional teaching hospital in southern Taiwan between 2006 and 2022. Demographic characteristics, family history, clinical features, and autoimmune comorbidities were extracted from electronic medical records. Associations between family history and clinical parameters were assessed using logistic regression analyses adjusted for age and sex. Results: A total of 157 patients (16.2%) reported a family history, more often through parents than grandparents; maternal history was more common than paternal. Compared with those without a family history, affected families showed significantly younger age at diagnosis and a higher prevalence of lower-limb involvement. In adjusted models, family history was associated with greater odds of lower-limb involvement (adjusted odds ratio [aOR] 1.78, 95% confidence interval [CI] 1.22–2.58) and lower odds of eyebrow/eyelash depigmentation (aOR 0.39, 95% CI 0.16–0.92). Hashimoto thyroiditis was more frequent among familial cases (aOR 7.56, 95% CI 1.23–46.65). In sex-stratified analyses, associations were stronger in females, notably for lower-limb involvement (aOR 1.87), axillary depigmentation (aOR 2.33), and Hashimoto thyroiditis (aOR 11.27). Conclusions: Familial vitiligo shows earlier onset, distinct anatomical patterns, and increased thyroid autoimmunity, supporting systematic family-history assessment and targeted thyroid screening. Full article
(This article belongs to the Special Issue Autoimmune Diseases: Advances and Challenges)
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10 pages, 254 KB  
Article
Lupus Anticoagulant Positivity as a Risk Marker for Hemolytic Anemia in Patients with APS
by Ji-Hyoun Kang
Medicina 2025, 61(8), 1364; https://doi.org/10.3390/medicina61081364 - 28 Jul 2025
Viewed by 1152
Abstract
Background and Objectives: Thrombocytopenia and hemolytic anemia are common but non-criteria manifestations of antiphospholipid syndrome (APS). However, their relationship with specific immunological profiles remains poorly characterized. This study aimed to evaluate these hematologic manifestations and identify their serological associations in patients with [...] Read more.
Background and Objectives: Thrombocytopenia and hemolytic anemia are common but non-criteria manifestations of antiphospholipid syndrome (APS). However, their relationship with specific immunological profiles remains poorly characterized. This study aimed to evaluate these hematologic manifestations and identify their serological associations in patients with APS. Materials and Methods: We retrospectively reviewed 346 patients diagnosed with APS. Demographic, clinical, and laboratory characteristics were analyzed. Logistic regression was used to identify risk factors associated with hemolytic anemia. Results: The mean age was 47.1 ± 13.1 years, and 71.7% were female. Thrombocytopenia was present in 34.5%, and hemolytic anemia in 16.5% of patients. Lupus anticoagulant (LAC) was the most common antibody (66.8%). In univariate analysis, hemolytic anemia was significantly associated with LAC positivity (OR 4.216, 95% CI: 2.326–7.640, p < 0.001), anticardiolipin IgG (OR 7.170, p = 0.007), triple positivity (OR 3.638, p = 0.002), and diabetes mellitus (OR 2.084, p = 0.007). DIAPS showed a protective trend (OR 0.547, p = 0.002). In multivariate analysis, only LAC remained an independent risk factor for hemolytic anemia (adjusted OR 3.557, 95% CI: 1.355–9.335, p = 0.003). Conclusions: LAC positivity is an independent predictor of hemolytic anemia in APS. These findings suggest a distinct immunologic profile among patients with hematologic involvement and highlight the need for further investigation into non-criteria manifestations. Full article
(This article belongs to the Special Issue Autoimmune Diseases: Advances and Challenges)
13 pages, 1353 KB  
Article
Mortality in Antinuclear Antibody-Positive Patients with and Without Rheumatologic Immune-Related Disorders: A Large-Scale Population-Based Study
by Uria Shani, Paula David, Ilana Balassiano Strosberg, Ohad Regev, Mohamad Yihia, Niv Ben-Shabat, Dennis McGonagle, Orly Weinstein, Howard Amital and Abdulla Watad
Medicina 2025, 61(1), 60; https://doi.org/10.3390/medicina61010060 - 2 Jan 2025
Cited by 5 | Viewed by 6186
Abstract
Background & Objectives: To explore the potential association between positive ANA serology and all-cause mortality in a large cohort of patients, including those with and without rheumatological conditions and other immune-related diseases. Material and Methods: A retrospective cohort study analyzed all-cause [...] Read more.
Background & Objectives: To explore the potential association between positive ANA serology and all-cause mortality in a large cohort of patients, including those with and without rheumatological conditions and other immune-related diseases. Material and Methods: A retrospective cohort study analyzed all-cause mortality among 205,862 patients from Clalit Health Services (CHS), Israel’s largest health maintenance organization (HMO). We compared patients aged 18 and older with positive ANA serology (n = 102,931) to an equal number of ANA-negative controls (n = 102,931). Multivariable Cox regression models were used to assess hazard ratios (HR) for mortality, adjusting for demographic and clinical factors. Results: ANA positivity was strongly associated with increased mortality (adjusted HR [aHR] 4.62; 95% CI 4.5–4.7, p < 0.001). Significant predictors of mortality included male gender (39.2% vs. 24.4%, p < 0.001), older age at testing (72.4 ± 13.0 vs. 50.1 ± 17.3 years, p < 0.001), and Jewish ethnicity (89.6% vs. 83.2%, p < 0.001). Certain ANA patterns, such as mitochondrial (and dense fine speckled (DFS-AC2)), were highly predictive of mortality, with aHRs of 36.14 (95% CI 29.78–43.85) and 29.77 (95% CI 26.58–33.34), respectively. ANA-positive patients with comorbid rheumatological immune-related disorders (RIRDs) demonstrated a higher survival rate compared to those without such a condition (aHR 0.9, 95% CI 0.86–0.95, p < 0.001). This finding remained significant after adjusting for several parameters, including age. Conclusions: ANA positivity is associated with increased all-cause mortality, particularly in individuals without rheumatologic disorders, after adjusting for confounders such as age. This may indicate occult malignancies, cardiovascular pathology, or chronic inflammatory states, necessitating more vigilant surveillance Full article
(This article belongs to the Special Issue Autoimmune Diseases: Advances and Challenges)
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15 pages, 3151 KB  
Case Report
Expanding the Genetic Framework: Insights into Non-HLA-B27 Contributions to Axial Spondylarthritis
by Ruxandra-Elena Nagit, Ioana Bratoiu, Corina Cianga, Mariana Pavel-Tanasa, Elena Rezus and Petru Cianga
Medicina 2025, 61(5), 793; https://doi.org/10.3390/medicina61050793 - 25 Apr 2025
Cited by 1 | Viewed by 1872
Abstract
Background and Objectives: Spondylarthritis is a complex group of inflammatory diseases closely associated with the HLA-B27 antigen. However, the role of non-HLA-B27 alleles in the disease’s pathogenesis has gained significant scholarly attention in recent years. Case presentation: This case study presents a [...] Read more.
Background and Objectives: Spondylarthritis is a complex group of inflammatory diseases closely associated with the HLA-B27 antigen. However, the role of non-HLA-B27 alleles in the disease’s pathogenesis has gained significant scholarly attention in recent years. Case presentation: This case study presents a 49-year-old male with a history of progressive inflammatory back pain, characterized by morning stiffness and restricted spinal mobility developed over several years. Initially presenting with non-specific symptoms, the patient eventually experienced persistent axial pain and deteriorating functional limitations, which required further evaluation. Radiographic imaging supported the diagnosis of ankylosing spondylitis (AS) by identifying bilateral sacroiliitis. HLA genotyping revealed a negative result for HLA-B27 but positive results for HLA-B13 and HLA-B37. This finding serves as a foundation for exploring alternative genetic factors contributing to spondylarthritis (SpA). HLA-B13 and HLA-B37 exhibit structural and functional similarities to HLA-B27, particularly in their peptide-binding grooves. This resemblance may lead to overlapping peptide repertoires and increased T cell cross-reactivity. Moreover, these alleles belong to overlapping cross-reactive groups (CREGs) and share the Bw4 epitope. This suggests that they may contribute to disease pathogenesis via similar mechanisms, such as molecular mimicry and the dysregulation of natural killer (NK) cell interactions, as observed in HLA-B27. Conclusions: This case emphasizes the necessity of expanding diagnostic criteria to incorporate non-HLA-B27 markers, particularly for patients who are HLA-B27-negative. Enhancing our understanding of the roles of alternative genetic markers can improve diagnostic accuracy, enable personalized treatment approaches, and enhance outcomes for the diverse SpA patient population. Full article
(This article belongs to the Special Issue Autoimmune Diseases: Advances and Challenges)
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