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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