Elevated Antibody Levels Research Articles

Warthin-like Papillary Thyroid Carcinoma: A Case Report and Review of the Literature.

Warthin-like subtype of papillary thyroid carcinoma (WLPTC) is a rare subtype of papillary thyroid carcinoma. This PTC subtype shows some pattern resemblance to Warthin tumors of the salivary gland, which confers its name but is a not genetically similar to salivary Warthin tumor, with the most frequent genetic change in WLPTC being BRAF p.V600E, the most frequent genetic driver of PTC. Warthin-like subtype of papillary thyroid carcinoma is found to have a favorable prognosis. We report a 44-year-old woman who presented with anterior neck swelling and elevated levels of antithyroid peroxidase antibodies. Fine-needle aspiration cytology showed features of papillary thyroid carcinoma and lymphocytic thyroiditis. On histopathological examination, thyroid follicular cells have oncocytic cytoplasm with infiltration of the tumor and fibrovascular cores by a dense lymphoplasmacytic infiltrate. Numerous multinucleated giant cells in the tumor are a notable feature. The final diagnosis is Warthin-like papillary thyroid carcinoma arising in association with chronic lymphocytic (Hashimoto) thyroiditis. Along with this case report, we perform a literature review of WLPTC between 2010 and 2024.

Irradiated whole cell Chlamydia vaccine confers significant protection in a murine genital tract challenge model.

Chlamydia trachomatis infections are the most common bacterial STIs globally and can lead to serious morbidity if untreated. Development of a killed, whole-cell vaccine has been stymied by coincident epitope destruction during inactivation. Here, we present a prototype Chlamydia vaccine composed of elementary bodies (EBs) from the related mouse pathogen, Chlamydia muridarum (Cm). EBs inactivated by gamma rays (Ir-Cm) in the presence of the antioxidant Mn2+-Decapeptide (DEHGTAVMLK) Phosphate (MDP) are protected from epitope damage but not DNA damage. Cm EBs gamma-inactivated with MDP retain their structure and provide significant protection in a murine genital tract infection model. Mice vaccinated with Ir-Cm (+MDP) exhibited elevated levels of Cm-specific IgG and IgA antibodies, reduced bacterial burdens, accelerated clearance, and distinctive cytokine responses compared to unvaccinated controls and animals vaccinated with EBs irradiated without MDP. Preserving EB epitopes with MDP during gamma inactivation offers the potential for a polyvalent, whole-cell vaccine against C. trachomatis.

Increased levels of antibodies to synaptopodin and annexin 1 in patients with primary podocytopathies.

Circulating anti-podocyte antibodies have been proposed as potential factors contributing to increased permeability in primary podocytopathies, such as Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS). The aim of the study was to to assess the levels of antibodies targeting synaptopodin and annexin 1 in the blood serum of patients diagnosed with nephrotic syndrome, with the aim of evaluating their potential utility in diagnosing primary podocytopathies and predicting therapeutic response. The study included a total of 72 patients diagnosed with nephrotic syndrome, alongside 21 healthy subjects for comparison. Among the patients, 38 were diagnosed with FSGS, 12 with MCD, and 22 with MN. The levels of anti-synaptopodin and anti-annexin-1 antibodies were quantified using Enzyme-Linked Immunosorbent Assay. The levels of antibodies to annexin 1 and anti-synaptopodin in the blood were found to be higher in patients diagnosed with MCD and FSGS compared to those with MN and healthy individuals. The elevated levels of antibodies to annexin 1 and synaptopodin showed area under the curve values of 0.826 (95% CI 0.732-0.923) and 0.827 (95% CI 0.741-0.879), respectively. However, a model incorporating both antibodies demonstrated higher sensitivity (80.9%) and specificity (81.3%) with an AUC of 0.859 (95% CI 0.760-0.957). Notably, serum levels of annexin 1 and anti-synaptopodin antibodies did not predict the response to prednisolone and/or CNI therapy. Levels of antibodies targeting synaptopodin and annexin 1 were notably elevated in patients diagnosed with MCD and FSGS compared to those with MN and healthy controls. A panel comprising both antibodies demonstrated moderate to high sensitivity and specificity for diagnosis MCD or FSGS.

CpG-adjuvanted virus-like particle vaccine induces protective immunity against Leishmania donovani infection.

Visceral leishmaniasis (VL) poses a significant public health challenge due to the lack of an approved human vaccine. We attempted to enhance the efficacy of virus-like particle vaccines expressing the Leishmania donovani promastigote surface antigen (LdPSA-VLP) by adjuvanting with CpG oligodeoxynucleotide (CpG-ODN). Here, adjuvanted vaccine-induced immune responses and their efficacies in mice challenged with mCherry-expressing L. donovani promastigotes were evaluated. Adjuvanted LdPSA-VLP vaccination significantly elevated parasite-specific IgG, IgG1, IgG2a, and IgG2b serum antibody levels. Additionally, vaccinated mice exhibited enhanced germinal center B cells and splenic T cell activities, compared to unimmunized mice. Importantly, adjuvanted LdPSA-VLPs reduced the levels of inflammatory cytokines IFN-γ and IL-6 in visceral organs, leading to decreased total parasite burden and protection against L. donovani challenge. Our findings indicate that CpG-ODN enhanced the protection conferred by LdPSA-VLPs, offering a promising step toward effective VL vaccine development.

Isolation and pathogenicity of a fowl adenovirus 8b (FAdV-8b) strain in Cherry Valley ducks

ABSTRACT Inclusion body hepatitis (IBH) is an economically important viral disease primarily affecting the poultry industry. In this study, we isolated a strain of FAdV-8b (strain SDYT) from naturally infected ducks and the hexon and fiber gene sequences were analysed by polymerase chain reaction (PCR) amplification. In order to study the pathogenicity of FAdV-8b in Cherry Valley ducks, we inoculated 10- and 20-day-old ducks with 0.3 ml of FAdV-4 virus (TCID50 of 105.5/0.1 ml) either orally or intramuscularly. Clinical signs, gross lesions and histopathological changes, cytokines, viral load and antibody levels were observed and recorded within 15 days after infection. Pathomorphological investigations revealed that ducks in the experimental group exhibited hepatitis. Histopathology showed multiple organ damage, including serious liver and kidney lesions. Furthermore, elevated levels of inflammatory cytokines and antibodies were noticed, due to the infection and innate immune response. At a later stage of infection, immunosuppression occurred, resulting in decreased levels of cytokines. Determination of viral load showed that the virus was present in several organs, with the highest viral DNA load found in the liver, followed by the kidney. Compared to birds infected orally, the intramuscular group exhibited the highest viral load. In summary, this study increases our understanding of the pathogenicity of FAdV-8b in ducks and establishes a model that will inform antiviral drug testing and vaccine evaluation for IBH, thereby preventing and reducing the spread of IBH in the poultry industry. RESEARCH HIGHLIGHTS A strain (SDYT) of fowl adenovirus 8b (FAdV-8b) was successfully isolated from ducks. Cherry Valley ducks were successfully infected with FAdV-8b. Different routes of infection can lead to duck mortality, more pronounced when birds are injected intramuscularly. FAdV-8b (SDYT) was distributed in various tissues and organs of ducks, causing different degrees of lesions.

Challenges and Considerations in Selecting Animal Models for Evaluating a Live, Cold-Chain-Free, Dual-Use Vaccine (MyChol) for Diarrhoeal Diseases: A Comprehensive Review.

Diarrhoeal diseases are the second leading cause of death for children under 5 years old in 69 low- and middle-income countries, with an annual economic burden of US$ 4 billion and over 525,000 lives lost. Cholera and enterotoxigenic Escherichia coli (ETEC) traveller's diarrhoea are major diarrhoeal diseases caused by Vibrio cholerae (O1 and O139 serogroups) and ETEC, which have similar pathogeneses and can co-infect. There is no exclusive vaccine for ETEC, but cholera vaccines containing the cholera toxin B (CT-B) component offer short-term cross-protection. However, licensed oral cholera vaccines are expensive due to cold-chain supplies and the need for multiple doses. A cost-effective, dual-protection, live, cold-chain-free vaccine is, therefore, required for vaccination campaigns in low-resource settings, and MyChol - a prototype cold-chain-free live attenuated cholera vaccine, targeting V. cholerae O139 and ETEC H10407 - was developed in this context. The vaccine was evaluated in three animal models (Sprague Dawley [SD] rats, BALB/c mice and New Zealand white rabbits) for safety, colonisation capacity, reactogenicity and immunogenicity against challenge strains. In suckling mice, MyChol displayed high colonisation potential compared to unformulated VCUSM14P (the vaccine candidate) and wild-type O139. In the acute toxicity assessment, the SD rats with the highest MyChol dose (1 × 107 colony-forming unit [CFU]/kg) demonstrated no adverse effects or mortality. Mice vaccinated with MyChol exhibited elevated antibody levels, including anti-CT, anti-heat-labile enterotoxin (LT), anti-CT-B and anti-LT-B. Anti-CT antibodies neutralised LT toxin in ETEC H10407 in challenge studies and cross-protected against ETEC H10407 in both mice and rabbits, preventing weight loss and diarrhoea. Ileal loop experiments in rabbits and BALB/c mice showed no reactogenicity. This review, based on our previous research, therefore provides valuable insights into improving the selection of animal models to advance preclinical evaluations of diarrhoeal vaccines.

12387 Late New-onset Graves' Orbitopathy: 14 Years Post-radioactive Iodine Treatment Of Graves' Disease: Case Report

Abstract Disclosure: F.F. Altaleb: None. K. Alaybaa: None. N. Aljohani: None. Introduction: Graves' orbitopathy (GO) is an autoimmune condition affecting the orbit and retro-ocular tissues, often accompanied by hyperthyroidism associated with Graves' disease, but it is rarely observed in euthyroid or hypothyroid individuals. Radioactive iodine (RAI) therapy for Graves' disease and smoking are recognized risk factors for GO development and progression. Individuals who smoke and undergo RAI treatment are significantly more likely to experience ocular lesions and worsening of GO compared to non-smokers. The exacerbation of GO post RAI therapy is attributed to elevated levels of TSH receptor antibodies, which may persist for up to a year post-treatment. Our case presents a rare occurrence of severe new-onset GO manifesting 14 years after achieving prolonged euthyroid status and successful RAI treatment for Graves' disease, accompanied by persistent TSH receptor antibody positivity that is unlikely to be suppressed by long term levothyroxine therapy. Clinical case: A 55-year-old male who’s a smoker and previously diagnosed with Grave’s hyperthyroidism, received treatment with RAI ablation therapy 14 years ago. At the time of diagnosis, there were no symptoms or signs of GO, and no history of thyroid eye disease was detected. Following the RAI treatment, he developed hypothyroidism and was promptly started on a daily dosage of 100 mcg of levothyroxine.Upon ocular examination: Visual acuity: 20/30 in both eyes. Significant restriction in extraocular muscle movements, with reported diplopia and pain. Bilateral lid retraction, proptosis, right conjunctival chemosis, and injection of the bulbar conjunctiva and caruncle, as well as lagophthalmos, were evident. No relative afferent pupillary defect observed. Color vision: 3/15 in the right eye, 15/15 in the left eye. Intraocular pressure: 22 mmHg (right eye), 16 mmHg (left eye). Optic discs unremarkable. Proptosis measurements: 26 mm (right eye), 23 mm (left eye). Ophthalmopathy clinical activity score: 7.Our laboratory analysis indicated normal thyroid function test However, the TSH receptor antibody and TPO antibody returned positive.We initiated treatment with IV methylprednisolone at a dosage of 500 Mg weekly for a duration of 4 weeks. Additionally, we introduced local measures, along with selenium supplementation. Within a week of initiating treatment, the conjunctival chemosis resolved, and there was improvement in ocular movement, resulting in mild to moderate restriction in all directions of gaze. Conclusion: This case illustrates the unexpected development of GO in a patient who had been euthyroid and effectively cured of Grave's disease for a span of 14 years following RAI treatment. The presence of TSH receptor antibodies, which are likely unresponsive to suppression by levothyroxine, as well as smoking cigarette might have contributed to the late new onset of the disease. Presentation: 6/3/2024

Recurrent tick bites induce high IgG1 antibody responses to α-Gal in sensitized and non-sensitized forestry employees in Luxembourg.

The α-Gal syndrome (AGS) is characterized by the presence of specific IgE-antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal). Sensitization to α-Gal has been associated with tick bites and individuals exposed to ticks have an elevated risk of sensitization. The aim of this study was to analyze IgG and IgE antibody responses to α-Gal in a high-risk cohort of forestry employees (FE) in Luxembourg. Questionnaires and serum samples of FE from Luxembourg (n=219) were retrospectively analyzed. α-Gal specific IgE was quantified by ImmunoCAP, α-Gal specific IgG and subclasses IgG1-4 were determined by ELISA. Additionally, sera from population-based controls (n=150) and two groups of food-allergic patients, patients with AGS (n=45) and fish-allergic patients (n=22) were assessed for IgG antibody responses to α-Gal and cod extract. Twenty-one percent of FE was sensitized to α-Gal (sIgE≥0.1kUA/L). Both sensitized and non-sensitized FE exhibited high levels of α-Gal specific IgG, IgG1 and IgG3 compared with controls, indicating a stimulation of IgG responses by recurrent tick bites, independent of the sensitization status. AGS patients had the highest levels of IgG1 and IgG2 antibodies, whereas the profile of fish-allergic patients was similar to the profile of the controls for which anti-α-Gal responses were dominated by IgG2 antibodies. α-Gal sIgG4 levels were either very low or undetectable in all groups. Our study provides evidence for a continuous stimulation of α-Gal related immune responses by repeated tick bites, translating into highly elevated levels of IgG1 antibodies directed against α-Gal.

Application of immunoinformatics to develop a novel and effective multiepitope chimeric vaccine against Variovorax durovernensis

Bloodstream infections pose a significant public health challenge caused by resistant bacteria such as Variovorax durovernensis, a recently reported Gram-negative bacterium, worsening the burden on healthcare systems. The design of a vaccine using chimeric peptides derived from a representative V. durovernensis strain holds significant promise for preventing disease onset. The current study aimed to employ reverse vaccinology (RV) approaches such as the retrieval of V. durovernensis proteomics data, removal of redundant proteins by CD-HIT, filtering of non-homologous proteins to humans and essential proteins, identification of outer membrane (OM) proteins by CELLO and PSORTb. Following these steps immunoinformatic approaches were applied, such as epitope prediction by IEDB, vaccine design using linkers and adjuvant andanalysis of antigenicity, allergenicity, safety and stability. Among the 4208 nonredundant proteins, an OmpA family protein (A0A940EKP4) was designated a potential candidate for the development of a multiepitope vaccine construct. Upon analysis of OM protein, six immunodominant (B cell) epitopes were found on the basis of the chimeric construct following the prediction of CTL stands cytotoxic T lymphocyte and HTL stands helper T lymphocyte epitopes. To ensure comprehensive population coverage globally, the CTL and HTL coverage rates were 58.18% and 46.56%, respectively, and 77.23% overall. By utilizing EAAAK, GPGPG, and AAY linkers, Cholera toxin B subunit adjuvants, and appropriate epitopes were smoothly incorporated into a chimeric vaccine effectively triggering both adaptive and innate immune responses. For example, the administered antigen showed a peak in counts on the fifthday post injection and then gradually declined until the fifteenth day. Elevated levels of several antibodies (IgG + IgM > 700,000; IgM > 600,000; IgG1 + IgG2; IgG1 > 500,000) were observed as decreased in the antigen concentration. Molecular dynamics simulations carried out via iMODS revealed strong correlations between residue pairs, highlighting the stability of the docked complex. The designed vaccine has promising potential in eliciting specific immunogenic responses, thereby facilitating future research for vaccine development against V. durovernensis.

Clinicopathological Features of CCDC6-RET and NCOA4-RET Fusions in Thyroid Cancer: A Single-Center Retrospective Cohort Study in a Chinese Population.

Background: The rearranged during transfection (RET) proto-oncogene fusion is common in papillary thyroid cancer (PTC), varying across ethnic groups. However, comprehensive comparisons of RET fusion types are limited. This study aims to identify predominant RET fusions and analyze their clinicopathological characteristics in a cohort of Chinese thyroid cancer cases. Methods: This single-center retrospective cohort study analyzed thyroid cancer data, utilizing next-generation sequencing on formalin-fixed, paraffin-embedded tissue samples. Detailed clinicopathological data of thyroid cancer cases with RET fusions were collected. Results: Among 2300 thyroid cancer cases, RET fusions were exclusively found in PTC or differentiated high-grade thyroid carcinoma (DHGTC) cases (2234 cases), absent in other types (66 cases). Of the 2234 PTC or DHGTC cases, 113 (5.06%) exhibited RET fusions, including 100 primary cases. Coiled-coil domain containing 6 (CCDC6)-RET fusions predominated (78.0%, 78/100), with nuclear receptor coactivator 4 (NCOA4)-RET fusions representing 22.0% (22/100). NCOA4-RET fusions were more prevalent in patients aged 45 years and older (54.5% vs. 28.2%, p = 0.021) and DHGTC cases (p < 0.05) and associated with higher rates of lymph node metastases (90.9% vs. 67.9%, p = 0.032). CCDC6-RET fusion exhibited a higher prevalence of Hashimoto's thyroiditis (HT) (67.9% vs. 22.7%, p < 0.001) and elevated thyroglobulin antibody levels (14.11 [1.86-174.32] IU/mL vs. 2.01 [1.14-15.41] IU/mL, p = 0.018). Moreover, CCDC6-RET fusion predominantly occurred in classical PTC (56.4%, 44/78) and infiltrative follicular PTC (17.9%, 14/78), whereas NCOA4-RET fusion was more frequent in classical PTC (36.4%, 8/22), solid PTC (27.3%, 6/22), and DHGTC (27.3%, 6/22). RET fusions with compound mutations were associated with older age (≥45 years) and bilateral thyroid involvement. Follow-up data showed a higher recurrence rate in the RET fusion group compared with the BRAFV600E mutation group (5.0% vs. 0.0%, p = 0.018). Although the NCOA4-RET group showed a numerically higher recurrence rate compared with CCDC6-RET (9.1% vs. 3.8%), this difference was not statistically significant (p = 0.559). Conclusions: RET fusions are specific to PTC or DHGTC cases among Chinese thyroid cancer cases. CCDC6-RET and NCOA4-RET fusions exhibited distinct clinicopathological features, with NCOA4-RET being more aggressive.

Clinical values of preoperative red blood cell distribution width and platelet parameters in patients with papillary thyroid carcinoma.

The prevalence of thyroid carcinoma is increasing, and papillary thyroid carcinoma (PTC) is the most frequent subtype. More and more attention is being concentrated on the association between inflammation indicators and malignant tumors. The aim of the present study was to analyze whether the preoperative red blood cell distribution width (RDW) and platelet parameters, including mean platelet volume (MPV) and platelet distribution width (PDW), can be applied to distinguish between patients with PTC or papillary thyroid microcarcinoma (PTMC) and healthy controls, and to explore the associations with clinicopathological characteristics. The study retrospectively compared the RDW, MPV and PDW values of 780 patients with PTC or PTMC against a healthy control group. Receiver operating characteristic (ROC) curves were conducted to determine diagnostic accuracy. Furthermore, the clinicopathological features of the patients with PTC or PTMC were compared between higher and lower platelet parameter groups based on the RDW, MPV and PDW values. Significantly higher preoperative RDW, MPV and PDW values were found in patients with PTC or PTMC compared with those of the healthy group. ROC curve analysis showed that the area under the curve (AUC) plus 95% confidence interval (95% CI) values of RDW, MPV and PDW were 0.808 (0.780-0.835), 0.771 (0.743-0.799) and 0.711 (0.681-0.742), respectively. When RDW and MPV were combined together, the AUC (95% CI) value was enhanced to 0.858 (0.835-0.881) for the patients with PTC. For the patients with PTMC, RDW, MPV and PDW had AUC (95% CI) values of 0.812 (0.783-0.840), 0.779 (0.749-0.808) and 0.718 (0.685-0.751), respectively. When RDW and MPV were combined together, the AUC (95% CI) value was enhanced to 0.858 (0.835-0.881). A higher RDW was significantly associated with being female, deeper tumor infiltration, and normal FT3 and FT4 levels. A higher PDW was significantly associated with elevated thyrotropin receptor antibody levels. In conclusion, as convenient and available inflammation indicators, RDW, PDW and MPV have diagnostic ability and can distinguish between patients with PTC or PTMC and healthy controls. In addition, the combined application of RDW and MPV can improve the diagnostic power. The values of RDW and MPV were associated with clinicopathological characteristics. To the best of our knowledge, this is the first study to prove the usefulness of preoperative RDW combined with MPV in diagnosing patients with PTC or PTMC.

Research Progress in the Treatment of IgG4-related Diseases in Chinese and Western Medicine

IgG4-related diseases (IgG4-RD) is a group of diseases characterized by abnormally elevated levels of IgG4 antibodies and infiltration of IgG4+ plasma cells. Currently, Western medicine mainly uses hormones, immunosuppressants, and biologically targeted therapies for treatment. Traditional Chinese medicine mainly uses dialectic therapy to treat the disease. The syndrome types are mostly Yin deficiency of the liver and kidney, phlegm and blood stasis, Yang deficiency of the spleen and kidney, and damp-heat of the liver and gallbladder. This article provides a review of the research progress in epidemiology, clinical manifestations, diagnosis, and treatment of IgG4-related diseases in Chinese and Western medicine.

A Case Report of Mixed Connective Tissue Disease Predominantly Manifesting as Systemic Sclerosis in a Middle-Aged Nepali Woman

Introduction: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disorder, first described in 1972, that presents with overlapping features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. The diagnosis of MCTD is complex and often delayed due to its varied clinical manifestations and the requirement of serological confirmation, particularly the presence of anti-U1 RNP antibodies. Despite its global prevalence, data on MCTD are limited, especially in the South Asian population.  Case Report: We present the case of a 42-year-old Nepali woman with a decade-long history of myalgia, muscle weakness, and joint pain, initially misdiagnosed as rheumatoid arthritis. Over time, she developed Raynaud phenomenon, dysphagia, and progressive muscle weakness, which prompted further investigation. Serological testing revealed elevated levels of anti-U1 RNP antibodies and a positive antinuclear antibody (ANA) titer, confirming the diagnosis of MCTD according to the Alarcón-Segovia criteria. The patient was successfully managed with a regimen of corticosteroids, hydroxychloroquine, and nifedipine, resulting in significant symptomatic improvement.  Discussion: This case underscores the diagnostic challenges associated with MCTD, a condition that may present with nonspecific symptoms and mimic other rheumatic diseases. The prolonged diagnostic journey of this patient highlights the need for heightened clinical suspicion and comprehensive serological testing in patients with overlapping connective tissue disease features. Furthermore, the case contributes to the limited body of literature on MCTD in the South Asian population, emphasizing the importance of early recognition and tailored management strategies to improve patient outcomes.  Conclusion: MCTD is a complex and under-recognized autoimmune disorder, particularly in the South Asian context. This case report highlights the importance of considering MCTD in the differential diagnosis of patients with multi-systemic involvement and underscores the role of serological testing in confirming the diagnosis. Early diagnosis and appropriate management are crucial in mitigating disease progression and improving the quality of life for patients with MCTD.

Right Ventricular Outflow Tract Mass as the Initial Presentation of Primary Antiphospholipid Syndrome

Abstract Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies and clinical manifestations, including thrombosis and pregnancy-related complications. While cardiac manifestations such as intracardiac thrombi, valvular disease, and intracardiac masses have been reported, the presentation of an intracardiac mass as the initial manifestation of primary APS (PAPS) is relatively uncommon. This case report describes a 40-year-old female patient who presented with an echogenic mass in the right ventricular outflow tract, subsequently diagnosed as a calcified amorphous tumor. Further investigation revealed elevated levels of anticardiolipin antibodies and beta-2 glycoprotein leading to the diagnosis of PAPS. The patient later developed digital ischemia, strengthening the suspicion of PAPS. This case highlights the importance of considering APS as a potential underlying cause for intracardiac masses, even in the absence of other typical manifestations. Early recognition and appropriate management, including anticoagulation and immunosuppressive therapy, are crucial to prevent further thrombotic complications and improve patient outcomes.

DENV Peptides Delivered as Spherical Nucleic Acid Constructs Enhance Antigen Presentation and Immunogenicity in vitro and in vivo.

The global prevalence of Dengue virus (DENV) infection poses a significant health risk, urging the need for effective vaccinations. Peptide vaccines, known for their capacity to induce comprehensive immunity against multiple virus serotypes, offer promise due to their stability, safety, and design flexibility. Spherical nucleic acid (SNA), particularly those with gold nanoparticle cores, present an attractive avenue for enhancing peptide vaccine efficacy due to their modularity and immunomodulatory properties. The spherical nucleic acid-TBB (SNA-TBB), a novel nanovaccine construct, was fabricated through the co-functionalization process of SNA with epitope peptide, targeting all four serotypes of the DENV. This innovative approach aims to enhance immunogenicity and provide broad-spectrum protection against DENV infections. The physicochemical properties of SNA-TBB were characterized using dynamic light scattering, zeta potential measurement, and transmission electron microscopy. In vitro assessments included endocytosis studies, cytotoxicity evaluation, bone marrow-dendritic cells (BMDCs) maturation and activation analysis, cytokine detection, RNA sequencing, and transcript level analysis in BMDCs. In vivo immunization studies in mice involved evaluating IgG antibody titers, serum protection against DENV infection and safety assessment of nanovaccines. SNA-TBB demonstrated successful synthesis, enhanced endocytosis, and favorable physicochemical properties. In vitro assessments revealed no cytotoxicity and promoted BMDCs maturation. Cytokine analyses exhibited heightened IL-12p70, TNF-α, and IL-1β levels. Transcriptomic analysis highlighted genes linked to BMDCs maturation and immune responses. In vivo studies immunization with SNA-TBB resulted in elevated antigen-specific IgG antibody levels and conferred protection against DENV infection in neonatal mice. Evaluation of in vivo safety showed no signs of adverse effects in vital organs. The study demonstrates the successful development of SNA-TBB as a promising nanovaccine platform against DENV infection and highlights the potential of SNA-based peptide vaccines as a strategy for developing safe and effective antiviral immunotherapy.

Association Between Antibodies That Bind Epstein-Barr Virus (EBV) gp350 and gH/gL and Shedding of EBV in Saliva From Nasopharyngeal Carcinoma Multiplex Family Members in Taiwan.

Elevated levels of Epstein-Barr virus (EBV) gp350 and gH/gL antibodies have been associated with a lower risk of developing nasopharyngeal carcinoma (NPC), although the evidence remains inconclusive and unexplained. We conducted a longitudinal study within a high-risk Taiwanese cohort, analyzing total immunoglobulin against EBV-gp350 and -gH/gL in blood and EBV DNA shedding in saliva. Contrary to our hypothesis-that elevated levels of antibodies previously shown to be associated with a lower NPC risk should result in a decrease in EBV shedding in saliva-higher anti-gp350 antibodies at baseline were significantly associated with detectable EBV DNA in saliva at follow-up (odds ratio [OR], 1.99 [95% confidence interval {CI}, 1.03-3.97]; P = .04). Higher anti-EBV-gH/gL antibodies at baseline were not significantly associated with risk of detectable EBV DNA at follow-up (OR, 0.69 [95% CI, .35-1.32]; P = .26). These findings underscore the complexity of virus-host interactions and emphasize the need for further investigations into their role in EBV-associated diseases.

Anti-TCP1 Antibody Is a Potential Biomarker for Diagnosing Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease caused by autoantibodies. Serum samples from patients with SLE (n = 10) were compared with those from normal controls (NCs, n = 5) using 21K protein chip analysis to identify a biomarker for SLE, revealing 63 SLE-specific autoantibodies. The anti-chaperonin-containing t-complex polypeptide-1 (TCP1) antibody exhibited higher expression in patients with SLE than in NCs. To validate the specificity of the anti-TCP1 antibody in SLE, dot blot analysis was conducted using sera from patients with SLE (n = 100), rheumatoid arthritis (RA; n = 25), Behçet's disease (BD; n = 28), and systemic sclerosis (SSc; n = 30) and NCs (n = 50). The results confirmed the detection of anti-TCP1 antibodies in 79 of 100 patients with SLE, with substantially elevated expression compared to both NCs and patients with other autoimmune diseases. We performed an enzyme-linked immunosorbent assay to determine the relative amounts of anti-TCP1 antibodies; markedly elevated anti-TCP1 antibody levels were detected in the sera of patients with SLE (50.1 ± 17.3 arbitrary unit (AU), n = 251) compared to those in NCs (33.9 ± 9.3 AU), RA (35 ± 8.7 AU), BD (37.5 ± 11.6 AU), and SSc (43 ± 11.9 AU). These data suggest that the anti-TCP1 antibody is a potential diagnostic biomarker for SLE.

Sex differences and risk factors of self-reported suicide attempts in middle-aged Chinese Han patients with first-episode drug-naïve anxious depression: a large-scale cross-sectional study.

This study aims to investigate sex differences and risk factors for self-reported suicide attempts among Chinese Han middle-aged patients with first-episode drug-naïve (FEDN) anxious depression (AD). A total of 1796 patients with FEDN major depressive disorder were enrolled in this study, including 341 middle-aged patients with AD. We compared the prevalence, demographics, and clinical characteristics of suicide attempts between male and female patients with FEDN middle-aged AD. We also explored the risk factors for self-reported suicide attempts in this population using binary logistic regression analysis. The male/female ratio was 91/250 and the age of onset was 51.50 ± 4.13. Our results showed that there were no significant sex differences in the prevalence of self-reported suicide attempts in middle-aged patients with FEDN AD. However, we did find significant differences in several demographic and clinical characteristics between self-reported suicide attempters and non-suicide attempters. Moreover, severe anxiety, measured by the Hamilton Anxiety Rating Scale score, was identified as a risk factor for self-reported suicide attempts in female middle-aged AD patients. Additionally, elevated thyroid peroxidase antibody (TPOAb) levels were linked to self-reported suicide attempts in male AD patients. Our findings suggest that there are no significant sex differences in the prevalence of self-reported suicide attempts in this population, but there may be sex-specific risk factors for self-reported suicide attempts in middle-aged AD. Clinical psychiatrists need to pay attention to thyroid hormone levels in middle-aged anxious depression.

Bioinformatics-Driven mRNA-Based Vaccine Design for Controlling Tinea Cruris Induced by Trichophyton rubrum.

Tinea cruris, a dermatophyte fungal infection predominantly caused by Trichophyton rubrum and Epidermophyton floccosum, primarily affects the groin, pubic region, and adjacent thigh. Its recurrence is frequent, attributable to repeated fungal infections in susceptible individuals, especially those with onychomycosis or tinea pedis, which act as reservoirs for dermatophytes. Given the persistent nature of tinea cruris, vaccination emerges as a promising strategy for fungal infection management, offering targeted, durable protection against various fungal species. Vaccines stimulate both humoral and cell-mediated immunity and are administered prophylactically to prevent infections while minimizing the risk of antifungal resistance development. Developing fungal vaccines is challenging due to the thick fungal cell wall, similarities between fungal and human cells, antigenic variation, and evolutionary resemblance to animals, complicating non-toxic target identification and T-cell response variability. No prior research has shown an mRNA vaccine for T. rubrum. Hence, this study proposes a novel mRNA-based vaccine for tinea cruris, potentially offering long-term immunity and reducing reliance on antifungal medications. This study explores the complete proteome of T. rubrum, identifying potential protein candidates for vaccine development through reverse vaccinology. Immunogenic epitopes from these candidates were mapped and integrated into multitope vaccines and reverse translated to construct mRNA vaccines. Then, the mRNA was translated and computationally assessed for physicochemical, chemical, and immunological attributes. Notably, 1,3-beta-glucanosyltransferase, CFEM domain-containing protein, cell wall galactomannoprotein, and LysM domain-containing protein emerged as promising vaccine targets. Antigenic, immunogenic, non-toxic, and non-allergenic cytotoxic T lymphocyte, helper T lymphocyte, and B lymphocyte epitopes were selected and linked with appropriate linkers and Toll-like receptor (TLR) agonist adjuvants to formulate vaccine candidates targeting T. rubrum. The protein-based vaccines underwent reverse translation to construct the mRNA vaccines, which, after inoculation, were translated again by host ribosomes to work as potential components for triggering the immune response. After that, molecular docking, normal mode analysis, and molecular dynamic simulation confirmed strong binding affinities and stable complexes between vaccines and TLR receptors. Furthermore, immune simulations of vaccines with and without adjuvant demonstrated activation of immune responses, evidenced by elevated levels of IgG1, IgG2, IgM antibodies, cytokines, and interleukins. There was no significant change in antibody production between vaccines with and without adjuvants, but adjuvants are crucial for activating the innate immune response via TLRs. Although mRNA vaccines hold promise against fungal infections, further research is essential to assess their safety and efficacy. Experimental validation is crucial for evaluating their immunogenicity, effectiveness, and safety.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.1.351 variant inactivated vaccine candidate (B.1.351V) generated strong binding and neutralizing antibody responses in BALB/c mice against the B.1.351 virus and other SARS-CoV-2 variants after two doses within 28 days. Immunized K18-hACE2 mice also exhibited elevated levels of live virus-neutralizing antibodies against various SARS-CoV-2 viruses. Following infection with these viruses, K18-hACE2 mice displayed a stable body weight, a high survival rate, minimal virus copies in lung tissue, and no lung damage compared to the control group. These findings indicate that B.1.351V offered protection against infection with multiple SARS-CoV-2 variants in mice, providing insights for the development of a vaccine targeting SARS-CoV-2 VOCs for human use.