Search Results (153)

Primary and secondary immunodeficiencies comprise a wide array of illnesses marked by immune system abnormalities, resulting in heightened vulnerability to infections, autoimmunity, and cancers. Notwithstanding progress in diagnostic instruments and an enhanced comprehension of the underlying pathophysiology, delayed diagnosis and underreporting persist as considerable obstacles. The implementation of artificial intelligence into clinical practice has surfaced as a viable method to enhance early detection, risk assessment, and management of immunodeficiencies. Recent advancements illustrate how artificial intelligence-driven models, such as predictive algorithms, electronic phenotyping, and automated flow cytometry analysis, might enable early diagnosis, minimize diagnostic delays, and enhance personalized treatment methods. Furthermore, artificial intelligence-driven immunopeptidomics and phenotypic categorization are enhancing vaccine development and biomarker identification. Successful implementation necessitates overcoming problems associated with data standardization, model validation, and ethical issues. Future advancements will necessitate a multidisciplinary partnership among physicians, data scientists, and governments to effectively use the revolutionary capabilities of artificial intelligence, therefore ushering in an age of precision medicine in immunodeficiencies. Full article

Background/Objectives: COVID-19 has been associated with a wide range of immune responses, including the production of autoantibodies, particularly in severe cases. This study investigates the IgG autoantibody responses in patients with varying severities of COVID-19 infection and compares these responses with vaccinated individuals. Methods: We utilized proteomic profiling to analyze autoantibody reactivity against a broad spectrum of proteins expressed in lymphoid and myeloid cell subsets in serum samples from severe and moderate COVID-19 patients, as well as vaccinated individuals who received the inactivated CoronaVac (Sinovac) vaccine. Results: Our findings indicate a marked increase in the diversity and number of IgG autoantibodies targeting intracellular and membrane-associated proteins in severe COVID-19 cases, compared to those with moderate cases of the disease. The autoantibody response in severe cases was found to primarily target proteins involved in immune cell activation, signaling, and differentiation, suggesting potential pathways of immune dysregulation and autoimmunity. In contrast, vaccinated individuals did not exhibit similar autoantibody reactivity, pointing to a more controlled immune response post-vaccination. Notably, no significant autoimmune responses were detected in the vaccinated cohort, suggesting that the inactivated vaccine does not induce autoreactive IgG. These findings align with the established safety profile of COVID-19 vaccines, especially in comparison to the heightened immune dysregulation observed in severe COVID-19 patients. The absence of a significant autoantibody response in vaccinated individuals supports the notion that vaccines, while inducing robust immune activation, do not typically trigger autoimmunity in healthy individuals. Conclusions: Our study underscores the importance of distinguishing between the immune responses triggered by infection and vaccination and highlights the need for the continued monitoring of autoimmune responses in severe COVID-19 cases. Future research should focus on the long-term persistence and clinical relevance of these autoantibodies, particularly in individuals with pre-existing autoimmune conditions or genetic predispositions. Full article

Rotavirus (RV) is the most common cause of severe acute gastroenteritis (AGE) in children under five years of age. This review summarizes current knowledge on RV infections, with a particular focus on viral structure, pathophysiological mechanisms, and age-dependent clinical presentation. Special attention is given to systemic manifestations, including central nervous system involvement, autoimmune responses such as type 1 diabetes and celiac disease, and rare associations with biliary atresia. The mechanisms of RV-induced diarrhea and vomiting are discussed in detail. Clinical severity scoring systems—such as the Vesikari and Clark scales—and dehydration assessment tools—the Clinical Dehydration Scale (CDS) and the Dehydration: Assessing Kids Accurately (DHAKA) score—are compared. The review highlights differences in disease course between children under and over five years, emphasizing that RV is not limited to early childhood. A major section addresses the global effectiveness of vaccination programs, their role in reducing disease burden, coverage challenges, and decreased efficacy in low-income countries. Particular focus is placed on high-risk groups, including preterm and immunocompromised infants. Full article

Background: Understanding immune response is essential for preparing for public health crises. COVID-19 vaccination provides robust immunity against SARS-CoV-2, but immunocompromised populations may have weaker immune responses. We assessed SARS-CoV-2 spike (trimer) total IgG/IgM/IgA (total Ig) to investigate immune response to COVID-19 vaccination in people living with HIV (PLWH), considering CD4⁺ T cell count, viral load, substance use, and comorbidities. Methods: This cross-sectional study was conducted in Miami, Florida, between May 2021 and December 2021 as part of the NIH Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) initiative (3U01DA040381-05S1) and the Miami Adult Studies on HIV (MASH) cohort (U01DA040381). Blood samples were collected and SARS-CoV-2 spike (trimer) total Ig was quantified. HIV serostatus, viral load, CD4⁺ T cell count, and COVID-19 vaccinations were abstracted from medical records. Substance use (tobacco, alcohol, and drug use [marijuana, cocaine, heroin, fentanyl, methamphetamine, amphetamine, hallucinogens, ecstasy, or misuse of prescription drugs]), and comorbidities (hypertension, diabetes, autoimmune disease, obesity, chronic kidney disease, and substance use disorders) were assessed via validated questionnaires. Drug use was confirmed via urine toxicology. Multivariable linear regression was conducted. Results: Median age (n = 1317) was 57.8 years, 49.8% were male, 50% were Black non-Hispanic, 66.2% had received ≥1 dose of a COVID-19 vaccine, and 29.6% were PLWH (71.3% virally suppressed and median CD4⁺ T cell count > 500 cells/µL). PLWH, compared to people without HIV, were more likely to have received ≥1 dose of a COVID-19 vaccine (76.2% vs. 62.0%, p < 0.001) and present with substance use (77.2% vs. 42.9%, p < 0.001) and comorbidities (72.8% vs. 48.2%, p < 0.001). Vaccinated PLWH, compared to unvaccinated PLWH, had higher CD4⁺ T cell counts (577.5 vs. 517.5, p = 0.011) and were more likely to be virally suppressed (76.4% vs. 54.8%, p < 0.001). A lower CD4⁺ T cell count (<200 vs. ≥500, β = −0.400, p = 0.033) and higher HIV viral load (≥200–<5000 vs. <200, β = −0.275, p < 0.001) were associated with lower spike (trimer) total Ig titers, indicating a diminished response to COVID-19 vaccination. Conclusions: A lower CD4⁺ T cell count and higher HIV viremia were linked to reduced SARS-CoV-2 immunogenicity in racial/ethnic minority PLWH, a population underrepresented in vaccine clinical trials. HIV care providers should target efforts to maintain viral suppression to avoid diminished responses to COVID-19 vaccination. Full article

The oral delivery of DNA/RNA nanoparticles represents a transformative approach in immunotherapy and vaccine development. These nanoparticles enable targeted immune modulation by delivering genetic material to specific cells in the gut-associated immune system, triggering both mucosal and systemic immune responses. Unlike parenteral administration, the oral route offers a unique immunological environment that supports both tolerance and activation, depending on the formulation design. This review explores the underlying mechanisms of immune modulation by DNA/RNA nanoparticles, their design and delivery strategies, and recent advances in their application. Emphasis is placed on strategies to overcome physiological barriers such as acidic pH, enzymatic degradation, mucus entrapment, and epithelial tight junctions. Special attention is given to the role of gut-associated lymphoid tissue in mediating immune responses and the therapeutic potential of these systems in oral vaccine platforms, food allergies, autoimmune diseases, and chronic inflammation. Despite challenges, recent advances in nanoparticle formulation support the translation of these technologies into clinical applications for both therapeutic immunomodulation and vaccination. Full article

Background/Objectives: Concerns about the occurrence of autoimmune diseases are one of the main reasons influencing the uptake of the human papillomavirus (HPV) vaccine. Limited evidence exists regarding the relationship between HPV vaccination and the risk of Hashimoto’s thyroiditis (HT). Therefore, the purpose of this study was to examine the association between HPV vaccination and the risk of HT development in American women. Methods: Using the National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2012, we conducted a cross-sectional study of 2717 women aged 18–59 with comprehensive data on relevant HPV vaccination status, HPV DNA vaginal swab results, and thyroid function. The relationship between HPV vaccination and the risk of HT development was explored by weighted logistic regression, while the association between HPV vaccination and thyroid peroxidase antibodies (TPOAb)/thyroglobulin antibodies (TGAb) levels was analyzed by weighted linear regression. Results: In the fully adjusted model, HPV vaccination was associated with an 87% decrease in the risk of developing HT (OR 0.13; 95% CI 0.02, 0.76). Furthermore, weighted linear regression demonstrated significant negative associations between HPV vaccination and TPOAb levels (−22.27 (−34.86, −9.68), p = 0.001) and TGAb levels (−7.53 (−14.88, −0.18), p = 0.045). HPV vaccination was significantly negatively correlated with the risk of HT development and TPOAb/TGAb levels. Conclusions: We advocate for adherence to vaccination guidelines, which could confer dual protective benefits against HPV and potentially reduce the risk of HT development. Full article

Background: HPV vaccination reduces the risk of anogenital warts, high-grade cervical intraepithelial neoplasia (CIN2+), and cervical cancer. To enhance immunogenicity, HPV vaccines include adjuvants such as toll-like receptor agonists, which may theoretically trigger autoimmune responses. However, existing data on this risk remain conflicting. This systematic review and meta-analysis assess the association between HPV vaccination and autoimmune disease onset in post-licensure controlled studies. Methods: A comprehensive literature search was conducted in Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library from inception to June 2024, following PRISMA guidelines. The study protocol was registered in PROSPERO (CRD42024606834). Results: A total of 356 studies were identified, including cross-reference reviews. Fourteen met inclusion criteria for qualitative and quantitative analysis, encompassing 8,088,838 patients, of whom 2,041,865 received the HPV vaccine. Conclusions: This meta-analysis found no significant association between HPV vaccination and autoimmune disease development. However, further large-scale observational studies are needed, particularly among male recipients, as current evidence is predominantly based on female populations. Future research should also evaluate risks for specific autoimmune disorders to refine the vaccine’s safety profile. Full article

Background: The Safety and Immunogenicity of COVID-19 Vaccines in Systemic Autoimmune-Mediated Inflammatory Diseases (SUCCEED) study was created to better understand COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Knowing the frequency of COVID-19 breakthrough infections is important, particularly in IMID. Our objective was to assess these events in IMID. Methods: We prospectively studied IMID participants who had received ≥three COVID-19 vaccine doses. Individuals provided saliva samples monthly (September 2022 to August 2023). These were evaluated by polymerase chain reaction (PCR) for SARS-CoV-2. We also assessed antibodies against SARS-CoV-2 (anti-spike, SmT1, receptor binding domain, RBD, and nucleocapsid, NP) based on dried blood spots. Multivariable general estimating equation regression produced odd ratios (OR) for PCR SARS-CoV-2 positivity, related to demographics, immunosuppressives, and antibody levels. Results: Diagnoses included rheumatoid arthritis RA (N = 161, 44% of the total), systemic lupus, psoriatic arthritis, spondylarthritis, vasculitis, systemic sclerosis, and inflammatory bowel disease. Of the 366 participants, most were taking immunosuppressive medication. Of 1266 saliva samples, 56 (5.1%) were positive for SARS-CoV-2 on PCR. Higher anti-SmT1 antibodies were inversely associated with SARS-CoV-2 detection on PCR (adjusted OR 0.66, 95% confidence interval 0.45–0.97). Antibodies to SmT1, RBD, and NP were correlated and thus could not be included in a single model, but when anti-RBD was used in place of anti-SmT1, the results were similar. No other factor (including prior COVID-19 infection) was clearly associated with SARS-CoV-2 detection. Conclusions: This is the first study of SARS-CoV-2 in a large prospective cohort of triple (or more) vaccinated individuals with IMIDs. Anti-SmT1 antibodies appeared to be protective against later SARS-CoV-2 positivity, although recent past infection was not clearly related. This suggests the importance of maintaining robust vaccine-induced immunity through vaccination in IMID. Full article

Preventive medicine has proven its long-term effectiveness and economic feasibility. Over the last century, vaccination has saved more lives than any other medical technology. At present, preventative measures against most infectious diseases are successfully used worldwide; in addition, vaccination platforms against oncological and even autoimmune diseases are being actively developed. At the same time, the development of medicine led to an increase in both life expectancy and the proportion of age-associated diseases, which pose a heavy socio-economic burden. In this context, the development of vaccine-based approaches for the prevention or treatment of age-related diseases opens up broad prospects for extending the period of active longevity and has high economic potential. It is well known that the development of age-related diseases is associated with the accumulation of senescent cells in various organs and tissues. It has been demonstrated that the elimination of such cells leads to the restoration of functions, rejuvenation, and extension of the lives of experimental animals. However, the development of vaccines against senescent cells is complicated by their antigenic heterogeneity and the lack of a unique marker. In addition, senescent cells are the body’s own cells, which may be the reason for their low immunogenicity. This mini-review discusses the mechanisms of central and peripheral tolerance that may influence the formation of an anti-senescent immune response and be responsible for the accumulation of senescent cells with age. Full article

Background: Emerging evidence suggests that SARS-CoV-2 infection and vaccines may trigger autoimmune responses in predisposed individuals. Idiopathic inflammatory myopathies (IIMs) are diseases with diverse clinical manifestations, often associated with myositis autoantibodies (MAs). Diagnosing IIM is challenging due to limitations in classification criteria and diagnostic assays. This study aimed to describe the incidence of IIM following SARS-CoV-2 infection or vaccination and compare rates between exposures. Methods: A multicenter observational study was conducted with 788 patients from 11 Spanish referral centers. A total of 1209 autoantibodies including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs), were analyzed using line blot immunoassay (LIA). Results: The study identified distinct patterns in aminoacyl-tRNA synthetase (ARS) antibody frequencies compared to pre-pandemic periods. Anti-PL-7 was the most prevalent ARS antibody (14.85%), while anti-Jo-1 was less frequent (7.23%). Anti-MDA5, commonly linked to SARS-CoV-2 infection, was detected in 11.68%. ANA positivity was observed in 60.66%, suggesting an autoimmune background. The most frequent diagnoses were anti-synthetase syndrome (ASSD) or IIM-non-ASSD (21.31%), followed by other systemic autoimmune diseases (SAIDs) (13.57%). Among the cohort, 91.13% received at least one dose of a messenger RNA (mRNA) COVID-19 vaccine, with a median of three doses per patient. Patients with prior SARS-CoV-2 infection or heterologous vaccination showed a higher frequency of multiple autoantibody positivity (p < 0.05), reflecting distinct immune signatures. Conclusions: This study provides valuable insights into the autoimmune risks and phenotypes associated with SARS-CoV-2 infection and vaccination, establishing a basis for further research on IIM and its link to MSAs and MAAs. Full article

The COVID-19 pandemic has encouraged the rapid development and licensing of vaccines against SARS-CoV-2. Currently, numerous vaccines are available on a global scale and are based on different mechanisms of action, including mRNA technology, viral vectors, inactive viruses, and subunit particles. Mass vaccination conducted worldwide has highlighted the potential development of side effects, including ones with skin involvement. This review synthesizes data from 62 manuscripts, reporting a total of 142 cases of autoimmune blistering skin diseases (AIBDs) following COVID-19 vaccination, comprising 59 cases of pemphigus and 83 cases of bullous pemphigoid. Among the 83 bullous pemphigoid cases, 78 were BP, with additional cases including 2 oral mucous membrane pemphigoid, 1 pemphigoid gestationis, 1 anti-p200 BP, and 1 dyshidrosiform BP. The mean age of affected individuals was 72 ± 12.7 years, with an average symptom onset of 11 ± 10.8 days post-vaccination. Notably, 59% of cases followed vaccination with BNT162b2 (Pfizer-BioNTech), 51.8% were new diagnoses, and 45.8% occurred after the second dose. The purpose of our review is to analyze the cases of pemphigus and bullous pemphigoid associated with COVID-19 vaccination and to investigate the pathogenetic mechanisms underlying the new development or flare-up of these diseases in association with vaccination. Our results show that the association between COVID-19 vaccines and AIBDs is a possible event. Full article

Celiac disease (CD) is an autoimmune disorder caused by gluten intake in genetically predisposed individuals. This article provides an overview of the available data on the risks of infectious diseases and the mechanisms involved in CD, including a detailed analysis of vaccine efficacy, immunogenicity, and safety. The published articles were retrieved from the PubMed database using the terms “celiac disease”, “efficacy”, “hyposplenism”, “immune response”, “infections”, “immunization”, “immunogenicity”, “safety”, “vaccination”, and “vaccine”. CD can be associated with several autoimmune diseases, including selective immunoglobulin A deficiency (SIgAD), altered mucosal permeability, and hyposplenism. These conditions entail an increased risk of infections, which can be prevented by targeted vaccinations, although specific recommendations on immunization practices for subjects with CD have not been released. Regarding vaccinations, the immune response to the Hepatitis B virus (HBV) vaccine can be impaired in patients with CD; therefore, proposed strategies to elicit and maintain protective specific antibody titers are summarized. For patients with conditions that put them at risk of infections, vaccinations against Pneumococcus and other encapsulated bacteria should be recommended. Based on the available evidence, the Rotavirus vaccine offered to children could be useful in preventing CD in at-risk subjects. Overall, except for the HBV vaccine, vaccine efficacy in patients with CD is comparable to that in the general population, and no safety concerns have arisen. Full article

Background: Myocarditis is a serious disease that has drawn increasing attention due to its association with COVID-19 and vaccination. This study investigates the epidemiology of myocarditis beyond the COVID-19 pandemic, including its incidence and outcomes over time. Methods: We analyzed the population-wide retrospective data from the Admitted-Patient-Data-Collection database of patients admitted to hospitals in New South Wales (NSW), Australia, with a diagnosis of myocarditis from 2001 to 2022. The incidence of myocarditis, changing classification of myocarditis over time, and complications of myocarditis over time were all calculated. Results: There were 4071 patients diagnosed with their first episode of myocarditis, with a median age of 42 years old, and 66% were male. The incidence of myocarditis in NSW has tripled over 20-years to 8.3 per-100,000-persons by 2022. Reactive myocarditis (i.e., myocarditis within 30-days of a respiratory or digestive illness) accounted for 38% of first presentations of myocarditis. Post COVID-19 myocarditis, a subset of reactive myocarditis, accounted for 42% of myocarditis admissions since the onset of the COVID-19 pandemic in Australia. Eight percent of patients had a background history of malignancy, and 6% had a history of autoimmune disease. In-hospital mortality was 4.5% during the entire study period but has been falling by 11% per year. During follow up, most readmissions for myocarditis occurred within 6-months; with 5.1% recurrence at 6-months compared to only 6.7% at 5-years. Conclusions: Myocarditis is an important condition with increasing incidence in Australia and with markedly changing characteristics in the pandemic and post pandemic era. Full article

Background/Objective: Biological females experience more autoimmune disease than males and more treatment-related adverse events (TRAEs) after immune checkpoint blockade therapy. However, little is known about sex-related differences in TRAEs after cancer vaccines. Methods: The Mel44 clinical trial (NCT00118274) enrolled 167 eligible patients with high-risk melanoma to treatment with either of two melanoma multipeptide vaccines. We hypothesized that females would experience higher rates and grades of TRAEs. TRAE rates and grades were compared between sexes, with adjustment for multiple comparisons, and with mixed-effects models. Results: Multiple sex-related differences in TRAE rate and grade were observed in unadjusted comparisons, but only hyperglycemia and hypopigmentation were significantly higher-grade by sex after correcting for multiple comparisons: they were increased in males. In mixed-effect models, vaccination strategy, but not patient sex, was independently associated with TRAE rates and grades. Conclusions: These data do not support our hypothesis that TRAEs would be increased in females. Vaccine safety was supported for both males and females. Full article

Narcolepsy type 1 (NT1) is an uncommon, persistent sleep disorder distinguished by significant daytime sleepiness, episodes of cataplexy, and irregularities in rapid eye movement sleep. The etiology of NT1 is linked to the destruction of hypothalamic neurons responsible for the synthesis of the wake-promoting neuropeptide known as hypothalamic orexin. The pathophysiological mechanisms underlying NT1 remain inadequately elucidated; however, a model that incorporates the interplay of genetic predisposition, environmental influences, immune system factors, and a deficiency in hypocretin (HCRT) provides a framework for elucidating the pathogenesis of NT1. The prevalence of NT1 has been observed to rise following influenza A (H1N1) pdm09 and the administration of the Pandemrix influenza vaccine. The strong association between narcolepsy and the HLA-DQB1*06:02 allele strongly indicates an autoimmune etiology for this condition. Increasing evidence suggests that T cells play a critical role in this autoimmune-mediated HCRT neuronal loss. Studies have identified specific T cell subsets, including CD4⁺ and CD8⁺ T cells, that target HCRT neurons, contributing to their destruction. Clarifying the pathogenesis of NT1 driven by autoimmune T cells is crucial for the development of effective therapeutic interventions for this disorder. This review examines the risk factors associated with the pathogenesis of NT1, explores the role of T cells within the immune system in the progression of NT1, and evaluates immune-mediated animal models alongside prospective immunotherapeutic strategies. Full article