Volume 10, Issue 2 (June 2026): In Progress

Autoimmune manifestations of primary minor immunodeficiencies (PMDs)—highly prevalent conditions that may represent a population-level model of autoimmunity—have not been systematically analyzed. The study aims to evaluate the current evidence for associations between PMDs and autoimmune syndromes. A systematic search of PubMed (MEDLINE) for 1980–2025 was conducted using keywords related to PMDs and autoimmune syndromes. The search was performed in two stages: an initial broad screening and a subsequent refined search with specific disease-related terms. High-quality peer-reviewed studies most relevant to the study objectives were selected. Available evidence indicates that PMDs commonly manifest through autoimmune syndromes according to a principle of universality, with important geographic, ethnic, age-related, sex-related, and ontogenetic variation. The strength of PMD–autoimmunity associations varies widely, reflecting major heterogeneity in both disease mechanisms and study quality. Key factors influencing clinical and epidemiological findings include terminological inconsistencies, multiple autoimmune pathways, heterogeneity of PMD origin and evolution, overlap with other immunodeficiencies and comorbidities, variability of clinical phenotypes, difficulties distinguishing PMDs from secondary immunosuppression, and the absence of standardized diagnostic criteria for many PMDs. Elementary models of autoimmune induction in immunocompromised individuals are proposed, together with a framework for personalized assessment of autoimmune disease in the context of PMDs, and implications for rational immunotherapy are discussed. PMDs are associated with diverse autoimmune syndromes and likely represent a major etiological factor of human autoimmunity at the population level. However, this data should be validated in further studies.

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The study evaluates the relationship with diabetes self-management behavior and retinal microvascular status and hypothesizes whether HbA1c has an indirect statistically significant association between diabetes self-management behavior and retinal microvascular status in individuals with type 2 diabetes. The second view is to determine whether the involvement of continuous glucose monitoring is a moderator of the relationship between the self-management behavior and the HbA1c. An empirical cross-sectional study involved 328 adults with type 2 diabetes. The model combined six indicators of self-management, three of the HbA1c indicators, four indicators of the Optical Coherence Tomography Angiography (OCTA)-based retinal microvascular indicators, and four indicators of the continuous glucose monitor activity. A Partial Least Squares Structural Equation Modeling (PLS-SEM) model was developed in Python and evaluated based on reliability, convergent and discriminant validity, bootstrapped path estimation, indirect effect test, moderation analysis, and predictive analysis. Better self-management behavior is related to lower HbA1c (β = −0.496, p = 0.001) and more desirable retinal microvascular situation (β = −0.144, p = 0.002). Worse retinal microvascular status was linked with higher levels of HbA1c (β = 0.584, p < 0.001). The self-management behavior indirectly related to retinal microvascular status via HbA1c was significant (β = −0.290, p < 0.001), and this could be attributed to partial mediation. The constant glucose monitoring involvement had a significant moderate effect on the association between self-management behavior and HbA1c (β = −0.120, p = 0.004). The results substantiate a composite behavioral, metabolic, and retinal imaging model with self-management behavior, HbA1c, and OCTA-generated retinal radiations being strongly correlated.

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The co-circulation of dengue virus (DENV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in endemic regions poses significant immunological challenges, particularly in the context of cross-reactivity and vaccine design. Leveraging an in-silico pipeline, this study sought to identify conserved antigenic determinants between DENV serotype 1 (DENV-1) and SARS-CoV-2 that may underlie molecular mimicry and immunological cross-reactivity. Viral protein sequences were obtained from UniProt, structurally modeled via SWISS-MODEL, and aligned using PRALINE. Conserved regions were mapped and visualized using PyMOL to identify accessible surface-exposed epitopes. Strikingly, up to 42% sequence identity was observed between DENV-1 polyproteins and SARS-CoV-2 proteins, including the nucleoprotein (N), spike (S), and nonstructural proteins NS7a and NS7b. Several conserved patches displayed surface accessibility, reinforcing their potential to elicit cross-reactive B or T cell responses. These findings highlight a critical concern in co-endemic settings: pre-existing DENV immunity could alter the outcome of SARS-CoV-2 infection or vaccination through heterologous immune responses, potentially contributing to antibody-dependent enhancement (ADE) or atypical inflammatory profiles. From an immunotherapeutic perspective, the identification of shared epitopes underscores the need for precision design in vaccines and monoclonal antibody therapies to avoid unintended immunopathology. While this bioinformatic study provides a foundational framework for predicting cross-reactive epitopes, experimental validation using serological assays, neutralization tests, and T cell activation studies are imperative. Ultimately, a deeper understanding of DENV–SARS-CoV-2 molecular mimicry may inform the development of safer and more effective immunotherapeutic strategies in regions burdened by both pathogens.

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Neoantigen-based personalized vaccines have emerged as an important innovation in the field of precision oncology through utilizing unique tumor somatic mutations to stimulate a targeted anti-tumor immune response. Unlike common tumor antigens, neoantigens can be recognized by the immune system as foreign because they exist only on tumor cells and thus do not contribute to any autoimmune reactions as a result of central immune tolerance. The emergence of techniques in next-generation sequencing, mutational profiling, and bioinformatics has made it possible to precisely identify neoantigens. In addition, breakthroughs in vaccine technology, such as synthetic long peptides, dendritic cell vaccination, and nucleic acid vaccination, have facilitated its clinical application. Studies have shown that neoantigen-based personalized vaccines are safe and can induce potent T-cell-mediated anti-tumor immune responses, especially when combined with immune checkpoint inhibitors. Randomized trials have indicated their potential in decreasing cancer recurrence. There still remain some limitations in developing personalized neoantigen vaccines due to the problem of tumor heterogeneity, immune evasion, neoantigen prediction, immunosuppression environment in the tumors, and high cost and long manufacturing time for personalized vaccines. This paper provides an overview of current methods and new approaches for neoantigen identification and vaccine development.

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Inguinal hernia repair is performed over 20 million times annually, with outcomes reflecting mechanical reconstruction and immune activation. This study compared autoplasty and tension-free alloplasty for primary inguinal hernias, focusing on clinical outcomes and inflammatory responses. This prospective single-center study compared tissue-based autoplasty (Shouldice/Spasokukotsky) with tension-free mesh alloplasty (Lichtenstein) in 118 adults (mean age 46 ± 12.1 years; 93% male; autoplasty, n = 50; alloplasty, n = 68). Pain (verbal descriptor scale), complications, hospital stay, and systemic markers (C-reactive protein, neutrophil-to-lymphocyte ratio, interleukin-6, tumor necrosis factor-alpha, lymphocyte count) were assessed (p < 0.05). Alloplasty showed faster operation (48.4 ± 1.5 vs. 59.6 ± 2.6 min), less pain (day 1: 4.5 ± 0.5 vs. 5.7 ± 0.6; day 2: 1.1 ± 0.2 vs. 2.4 ± 0.3; day 5: 0.5 ± 0.1 vs. 1.2 ± 0.2), earlier walking (7.2 ± 2.1 vs. 21.4 ± 3.6 h), fewer complications (8.4% vs. 28.8%), and reduced hospitalization (3.6 ± 0.9 vs. 5.1 ± 1.2 days; all p < 0.05). Autoplasty showed higher inflammatory markers (C-reactive protein 32.5 ± 6.8 vs. 21.3 ± 5.4 mg/L; neutrophil-to-lymphocyte ratio 5.8 ± 1.2 vs. 3.9 ± 0.9; interleukin-6 48.7 ± 10.2 vs. 29.4 ± 8.6 pg/mL; tumor necrosis factor-alpha 26.5 ± 7.3 vs. 17.2 ± 5.8 pg/mL; all significant). Operative time was correlated with pain (r = 0.64; p < 0.01) and complications (r = 0.48; p < 0.05). Tension-free alloplasty improved recovery and reduced immune activation; however, non-randomization, single-center design, and limited follow-up constrain long-term inferences of the study.

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Acne vulgaris is a chronic inflammatory skin disease in which a defect in the immune barrier function is a major extent of the pathological etiology. The aim of this randomized controlled trial was to assess the restorative benefits of supramolecular salicylic acid (SSA) with intense pulsed light (IPL) photon rejuvenation and its effects on the immune barrier function of the skin in acne patients. Moderate-to-severe acne was assigned to each patient, with three groups being treated for 12 weeks with either: The primary outcome was transepidermal water loss (TEWL) (continuous variable); secondary outcomes were stratum corneum hydration, sebum secretion, skin pH, pro- and anti-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10, TGF-β), Treg/Th17 cell ratio, microbiome Shannon diversity index, Global Acne Grading System (GAGS) score, lesion counts, and the Dermatology Life Quality Index (DLQI). The SSA+IPL group showed significant improvements compared to both monotherapy groups in all outcomes (all corrected p < 0.001). TEWL decreased by 47.0% (Cohen's d = 2.14; 95% CI: 1.67–2.61), stratum corneum hydration increased by 67.0%, and sebum secretion declined by 45.7%. Fifty-six to 58% reduction in pro-inflammatory cytokines was achieved, whereas IL-10 and TGF-β levels increased by 167.8% and 130.8% respectively. The ratio Treg/Th17 was raised by 331.3% and Shannon diversity index was raised by 52.1%. This multiple regression revealed that the Treg/Th17 ratio reestablishment, reduction of sebum and upregulation of IL-10 are independent factors of clinical efficacy (adjusted R² = 0.763). The combination of SSA and IPL therapy can have a systemic effect on the regeneration of skin immune barrier function by overlapping mechanisms and deserves further testing in larger trials.

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Obesity is a global health and economic burden that affects disadvantaged groups and increases healthcare use. It involves adipocyte hypertrophy/hypoxia, adipokine imbalance, immune cell recruitment, pro-inflammatory polarization, signaling activation, systemic inflammation, oxidative stress, insulin resistance, and a higher cardiometabolic risk. This review synthesizes bariatric surgery as an immunometabolic intervention, integrating mechanistic, clinical, and translational findings. A literature search of PubMed/MEDLINE, Scopus, and Web of Science (through 2025), supplemented by Google Scholar, included peer-reviewed human and animal studies on metabolic or immunological mechanisms; technical surgical reports and non-peer-reviewed sources were excluded. Bariatric surgery consistently achieves broader metabolic and immunomodulatory, sustained weight loss and improved glycemic control and comorbidity profiles. Diabetes improvements partially preceded major weight loss via enhanced enteroinsular signaling, altered bile acid pathways, and microbiome remodeling. Surgery reduces systemic inflammation, reprograms cytokines, improves immune cell phenotypes, and lowers oxidative stress, leading to antioxidant status recovery. Comparative evidence indicates an efficacy–risk gradient: laparoscopic adjustable gastric banding is least effective; laparoscopic sleeve gastrectomy offers intermediate benefits with favorable safety; Roux-en-Y gastric bypass is widely supported with strong outcomes and manageable risks; and biliopancreatic diversion with duodenal switch yields maximal benefit but higher adverse-event and malabsorption burden. Bariatric surgery is an immunometabolic intervention that induces immune and metabolic remodeling, disrupting the obesity–inflammation–insulin resistance cycle via multi-system remodeling.

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Global organ shortages have intensified interest in donation after circulatory death (DCD). However, DCD kidneys are affected by warm ischemia, which amplifies ischemia-reperfusion injury via a reactive oxygen species-damage-associated molecular pattern-cytokine-endothelial cascade, increasing the risk of microvascular dysfunction and delayed graft function. This study developed an objective postmortem ex vivo model to compare asystolic early donors/rapid death (AED; warm ischemia ≤30 min) and asystolic extended/delayed donors (ASED; 60–120 min) using integrated morphofunctional, biochemical, and immuno-inflammatory indicators during hypothermic perfusion. In an ex vivo design, 145 DCD renal allografts (71 AED, 74 ASED) underwent standardized hypothermic rehabilitation, with evaluations at 30, 60, and 120 min. Oxidative stress was quantified by lipid peroxidation and antioxidant capacity, in addition to histopathology (tubular, endothelial, podocyte, nuclear injury) and composite indices for cytokine activation, endothelial injury, and immune activation. A multicriteria scoring algorithm was used to categorize rehabilitation effectiveness, and group differences were assessed using comparative tests. These findings support a dynamic, multicriteria viability framework, indicating that ASED kidneys are at a higher risk yet potentially salvageable under comprehensive perfusion rehabilitation, warranting prospective transplantation-linked validation. Lipid peroxidation increased over time, rising more in the ASED group, whereas glutathione showed limited compensatory change. The ASED kidneys demonstrated greater tubular degeneration, endothelial swelling, podocyte injury, and nuclear alterations, with higher oxidative, inflammatory, and immune activation scores. Despite the higher biological burden, positive integrated outcomes remained frequent (AED 89.2% vs. ASED 84.5%; RR: 0.982; OR: 1.07–1.16), and morphology-function correlations were strong (AED r = 1.0; ASED r = 0.9). These findings support a dynamic, multicriteria viability framework, indicating that ASED kidneys are at a higher risk yet potentially salvageable under comprehensive perfusion rehabilitation, warranting prospective transplantation-linked validation.

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