Search Results (6,109)

Background/Objectives: IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide; it is characterized by a complex pathophysiology involving several inflammatory pathways. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may be critical in this process. This study aimed to investigate the role of this pathway in IgAN and examine related tissue inflammatory markers. Methods: We analyzed 63 biopsy-confirmed patients with IgAN and performed immunohistochemical analysis on renal samples. A panel of antibodies targeting the JAK/STAT pathway, including JAK2, JAK3, p-STAT, STAT3, and MAPK/ERK, was used for this analysis. Six kidney tumor border samples were used as controls. Additionally, CD68 staining was used to evaluate tissue inflammation in the kidney biopsies. Results: Patients with IgAN showed a significantly higher cellular density of JAK3 staining at the glomerular level compared to controls, indicating JAK3 activation (p < 0.0002). Nevertheless, the correlation between JAK3 positivity in glomeruli and clinical parameters such as the initial and final estimated glomerular filtration rate (eGFR) and proteinuria was not statistically significant. Identical results were obtained with CD68+ macrophage counts in the glomerular compartment, which did not show any correlation with clinical parameters, while CD68+ tubulointerstitial staining demonstrated a significant correlation with both initial (p = 0.002) and final eGFRs (p = 0.0014), proteinuria (p = 0.010), and interstitial fibrosis (p < 0.001), as well as with renal disease progression (p = 0.005). Conclusions: Activation of the JAK/STAT pathway was observed in patients with IgAN relative to controls, notwithstanding the inability to assess the full pathway due to technical limitations. Macrophage CD68 staining in the tubulointerstitial area increased and was associated with clinical and laboratory parameters such as eGFR and proteinuria. Additionally, MEST-C histological parameters, such as segmental glomerulosclerosis (S0/S1), tubular atrophy/interstitial fibrosis (T0/T1/T2), and crescents (C0/C1/C2), were associated with a higher number of CD68+ cells. Full article

Snakebite envenoming remains a critical public health issue, and the molecular variability of venoms limits the cross-species efficacy of conventional antivenoms. Here, we conducted a comparative proteomic analysis of Bitis arietans venom to identify conserved peptide regions derived from enzymatic toxins and evaluate their potential relevance for complementary immunotherapeutic applications. Enzyme-enriched venom fractions were isolated through sequential affinity and ion-exchange chromatography and were subsequently characterized using fluorogenic FRET substrates and inhibitor assays. LC–MS/MS analysis identified 1099 proteins and revealed 36 conserved peptides within snake venom metalloproteinases (SVMPs), serine proteases (SVSPs), and phospholipase A₂ (PLA₂), particularly located near catalytic residues and structurally essential motifs such as the HExxHxxGxxH zinc-binding site in SVMPs, the His-Asp-Ser catalytic triad in SVSPs, and the Ca²⁺-binding loop in PLA₂, across Viperidae venoms. These conserved regions were also observed in homologous toxin isoforms from additional Viperidae genera, supporting the evolutionary conservation of key functional domains. While sequence conservation alone does not guarantee neutralization capacity, the identified regions represent strong candidates for structural epitope mapping and targeted antibody development. This study provides a peptide-level framework for advancing complementary antibody-based therapies designed to broaden cross-species toxin recognition, reduce antivenom dosage requirements, and improve clinical outcomes in snakebite envenoming. Full article

Background: Experimental autoimmune thyroiditis is an important animal model for studying Hashimoto’s thyroiditis. Our aim was to develop the model using CBA/J-DR3 mice expressing human HLA-DR3, which is associated with autoimmune thyroiditis in humans, to better simulate human autoimmune thyroiditis. Such a humanized model can be used to test specific antigen therapies for autoimmune thyroiditis. Methods: CBA/J-DR3 mice were produced by back-crossing B6-DR3 mice to the CBA/J background. Female CBA/J-DR3 mice were immunized with human thyroglobulin (Tg) in complete Freund’s adjuvant on days 0 and 7. On day 21, mice were sacrificed, blood collected, spleen and thyroid harvested for analysis. Splenocytes were analyzed for T cell responses to Tg and its major T-cell epitope in human autoimmune thyroiditis, Tg.2098. Serum anti-thyroglobulin antibodies were measured by ELISA, and thyroid-stimulating hormone was measured using the Luminex assay. Thyroid histology and immunohistochemistry were examined. Results: Immunized CBA/J-DR3 mice showed significant T cell proliferation in response to Tg (stimulation index 3.4 ± 4.5) and Tg.2098 (1.5 ± 0.7). Anti-thyroglobulin antibody levels were elevated in immunized mice when compared to control mice (2.05 ± 0.75 vs. 0.15 ± 0.06, p < 0.0001). T cells demonstrated higher reactivity to thyroid antigens by enhanced production of pro-inflammatory cytokines. Thyroid immunohistochemistry revealed mild CD3-positive T-cell infiltration. Conclusions: This novel humanized CBA/J-DR3 mouse model of Hashimoto’s thyroiditis demonstrates key features of human autoimmune thyroiditis. The HLA-DR3 background and the immune response to Tg and Tg.2098 enhance translational relevance, making this a valuable model for studying thyroid disease pathogenesis and testing targeted immune-modifying therapies. Full article

Chronic arthritis following arthritogenic alphavirus infections presents symptoms resembling autoimmune rheumatic diseases, raising questions about the underlying mechanisms, including molecular mimicry and autoantibody production. This systematic review evaluated evidence supporting molecular mimicry and the potential role of autoantibodies as predictive biomarkers in alphavirus-induced chronic arthritis. A comprehensive search of PubMed, Scopus and Web of Science was conducted following PRISMA 2020 guidelines and PECO framework. Thirteen studies met the inclusion criteria: four computational studies assessing peptide homology between viral and human proteins, and nine clinical studies evaluating autoantibodies in chronic post-alphavirus arthritis. Computational analyses identified conserved alphavirus peptides with sequence and structural similarity to human proteins implicated in autoimmunity, supporting the hypothesis of molecular mimicry. However, most lacked experimental validation. Clinical studies showed variable detection of autoantibodies, rheumatoid factors, anti-cyclic citrullinated peptide, and antinuclear antibodies in chronic patients, though seropositivity rates were inconsistent and generally low. Only one study reported a significant association between autoantibody levels and disease chronicity. The findings suggest a potential autoimmune component in post-alphavirus arthritis driven by molecular mimicry, though current evidence remains inconclusive due to methodological heterogeneity and limited validation. Autoantibodies may contribute to pathogenesis but are not reliable predictors of chronicity. Future longitudinal studies with standardized assays and validation of computational findings in human models are needed. Full article

Introduction: Cholera remains a major public health threat in endemic settings, and oral cholera vaccine (Shanchol™) campaigns are increasingly used amid constrained global supply. However, practical decisions on revaccination require clearer, setting-specific estimates of how rapidly vaccine-induced vibriocidal antibodies peak and wane. Methods: We conducted a prospective cohort kinetics analysis in Lukanga Swamps (Central Province, Zambia), enrolling adults (18–65 years) stratified by prior Shanchol™ exposure (0, 1, or 2 previous doses). All participants received two Shanchol™ doses 14 days apart, with serum collected at baseline and days 14, 28, 60, and 90 (end of follow-up). Ogawa and Inaba vibriocidal titres were measured using a complement-based assay and analysed on the log10 scale. Serotype-specific mixed-effects models with natural cubic splines for time (knots: 14, 28, 60 days) assessed trajectories by prior-dose strata, adjusting for age, sex, and HIV status. Peak timing and post-peak half-life were derived from model-based predictions with participant-level bootstrap CIs (1000 replications). Results: The analysis included 225 participants: 68 (30.2%) with zero prior doses, 89 (39.6%) with one, and 68 (30.2%) with two; median age was 33 years (IQR 25–49), 56.4% were female, and 19.2% were HIV-positive. Modelled titres for both serotypes rose steeply after vaccination, peaking around day 36–37 across prior-dose strata. Ogawa titres reached half of peak by about day 73–78, corresponding to post-peak half-lives of 37–41 days; Inaba declined more slowly with half-lives of 42–46 days. Confidence intervals overlapped across prior-dose strata, indicating minimal differences by vaccination history. Conclusions: In this cholera-endemic adult population, Shanchol™ induced vibriocidal responses that peaked at ~5 weeks and waned over the following 5–7 weeks, with broadly similar kinetics regardless of prior vaccination and slightly slower decay for Inaba than Ogawa. These parameters can inform booster timing in hotspot settings. Full article

Background: ExPEC9V is a 9-valent vaccine candidate designed to prevent invasive Escherichia coli disease, a life-threatening condition occurring when extraintestinal pathogenic E. coli (ExPEC) invade sterile sites. We evaluated immunogenicity and safety when ExPEC9V was co-administered with high-dose (HD) quadrivalent seasonal influenza vaccine. Methods: This Phase 3, double-blind, placebo-controlled study (NCT06134804) randomized 959 adults (≥65 years) to receive co-administration of ExPEC9V and HD quadrivalent seasonal influenza vaccine (CoAd) or each vaccine alone, 29 days apart (Control). Co-primary objectives were non-inferiority of co-administration versus separate administration following predefined criteria based on influenza strain-specific hemagglutination inhibition (HAI) antibody titers and ExPEC9V O-serotype binding antibody levels (multiplex electrochemiluminescence-based immunoassay), 29 days post vaccination. Reactogenicity and safety were assessed. Results: Co-administration of ExPEC9V with HD influenza vaccine demonstrated non-inferiority (upper bound of 2-sided 95% confidence interval [CI] < 1.5 for HAI geometric mean ratio [Control/CoAd]) for all influenza strains. Non-inferiority for ExPEC9V O-serotype antibody levels was not demonstrated (upper bound 95% CI > 1.5). One of nine serotypes met the non-inferiority criterion; eight did not, with four narrowly failing to meet the non-inferiority criterion. ExPEC9V immunogenicity was similar regardless of urinary tract infection history. ExPEC9V was safe and well tolerated, with no serious adverse events related to ExPEC9V. Reactogenicity rate was higher with co-administration. Conclusions: Co-administration of ExPEC9V with HD influenza vaccine met non-inferiority criteria of humoral immune responses for influenza antigens, but not for ExPEC9V O-serotype antigens. ExPEC9V, administered alone or with HD influenza vaccine, was safe and well tolerated, with an acceptable reactogenicity profile. Full article

Background: The human leukocyte antigen (HLA) is crucial for antigen presentation and vaccine efficacy. This study examined the association between HLA polymorphisms and the immune response to hepatitis B vaccination in children with acute lymphoblastic leukemia (ALL). Methods: 101 pediatric ALL patients at Shanghai Children's Medical Center affiliated with Shanghai Jiaotong University School of Medicine who tested negative for hepatitis B surface antibody (anti-HBs) and were not infected with hepatitis B received three doses of the hepatitis B vaccine. Anti-HBs titers were measured before and after vaccination. Participants were divided into high- and low-response groups based on post-vaccination anti-HBs titers. Sequence-specific primer polymerase chain reaction (PCR-SSP) was used to genotype HLA-A, -B, -Cw, -DRB1, and -DQB1 alleles. Results: Pre-vaccination anti-HBs titers were 3.38 ± 2.97 mIU/mL, and the post-vaccination seroconversion rate was 100% with mean titers of 429.61 ± 303.13 mIU/mL (p < 0.001). Following immunization, the low-response group (11.88%) had an anti-HBs titer of 56.47 ± 28.38 mIU/mL, while the high-response group (88.12%) had an anti-HBs titer of 479.93 ± 287.70 mIU/mL. There were significant differences in allele frequencies of B*3501 and Cw*0303 between the two response groups (p < 0.05). Binary logistic regression analysis showed that the B*3501 allele was negatively correlated with the anti-HBs response level (p < 0.05). Conclusions: HLA-B*3501 may be associated with lower antibody response levels in children with ALL who completed the full hepatitis B vaccination series. All these children demonstrated protection against the hepatitis B virus (HBV). We will subsequently validate the association between HLA-B*3501 and the level of hepatitis B vaccine immune response in children with ALL through expanding the sample size or conducting a multicenter study. Full article

The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by profound immune dysregulation where interleukins play a central role in determining disease severity and response to interventions. This review summarizes the role of interleukins in the immunopathogenesis of COVID-19, with particular emphasis on differences observed across major SARS-CoV-2 variants. Pro-inflammatory interleukins like IL-1β, IL-6, IL-2, IL-17 and IL-18 are critically involved in cytokine storm, hyperinflammation, and acute respiratory distress syndrome, whereas anti-inflammatory cytokines like IL-10 contribute to immune regulation and resolution of inflammation. Elevated levels of IL-1α, IL-1β, IL-4, IL-8, IL-9, IL-16, IL-18 have been documented in the Delta variant as compared with the Omicron variant, with IL-6 being the most frequent interleukin reported to be increased across all SARS-CoV-2 variants relative to the ancestral Wuhan strain. Elevated IL-2, IL-4, IL-6, and IL-10 levels have been associated with Omicron sub-variants. The review encompasses interleukin-based therapeutic strategies, where several IL-1 and IL-6 inhibitors were studied across clinical trials, but only tocilizumab has shown some promise against severe COVID-19. IL-2, IL-6, IL-15 and IL-21 levels were positively correlated with IgG and neutralizing antibody activity after vaccination with longevity of post-vaccination immunity being determined by IL-2 and IL-7. Full article

Background/Objectives: Interleukin-17A (IL-17A) is a key pathogenic cytokine in autoimmune arthropathies. Current monoclonal antibody inhibitors targeting the IL-17/IL-17RA axis demonstrate clinical efficacy but face significant limitations, including immunogenicity, the loss of therapeutic response, and cold-chain storage. Our study evaluated oligonucleotide aptamers targeting IL-17A and its receptor as an alternative to monoclonal antibodies to suppress an IL-17A-induced inflammatory response in cell models relevant to immunoinflammatory rheumatic diseases. Methods: We examined three aptamers: 2′-F-RNA aptamers Apt21-2 and Apt3-4 specific to IL-17A and DNA aptamer RA10-6 targeting the receptor of IL-17A. Their ability to suppress IL-17A functional activity was assessed in peripheral blood mononuclear cells (PBMCs) from healthy donors and personalized fibroblast-like synoviocytes (FLSs) from patients with axial spondyloarthritis (axSpA) and rheumatoid arthritis (RA). Inhibition was measured by quantifying IL-6 and MMP-13 secretion using ELISA and flow cytometry, using secukinumab as a reference control. Results: In PBMC, all aptamers suppressed IL-17A-stimulated IL-6 secretion and cell proliferation in a concentration-dependent manner (17–200 nM), with a 65–85% efficacy, comparable to that of secukinumab. In axSpA-derived FLS, we observed time-dependent efficacy: At 4 h, all three aptamers suppressed IL-6 to the same extent as secukinumab; at 24 h, RA10-6 maintained high efficacy while Apt21-2 and Apt3-4 showed reduced activity. A combination of receptor-targeting RA10-6 with anti-IL-17A aptamers resulted in synergistic IL-6 suppression. All aptamers reduced MMP-13 to basal levels. RA-derived FLS showed diminished responses to all inhibitors. Conclusions: Aptamers demonstrate high specificity and sustained efficacy in suppressing IL-17A signaling for an in vitro model of spondyloarthritis, with superior performance over antibodies. Disease-dependent differential efficacy in RA FLS reflects heterogeneity consistent with limited clinical anti-IL-17 efficacy in RA. These findings show the strong potential of the studied aptamers as an alternative to monoclonal antibodies for IL-17-associated inflammatory arthropathies, particularly spondyloarthritis. Full article

Micronutrient status is recognized to influence host susceptibility to viral infections, yet its impact on Zika virus (ZIKV) pathogenesis remains incompletely understood. We investigated the effects of dietary selenium and combined selenium plus vitamin E deficiency on ZIKV infection outcomes in a type I interferon α/β receptor knockout (Ifnar1^−/−) murine model. Mice maintained on deficient diets exhibited significantly lower neutralizing antibody titers and reduced levels of key antiviral cytokines (IFN-γ, TNF-α, IFN-α, IFN-β, IL-12p70, CCL5) compared to controls. Correspondingly, higher viral RNA loads were detected in the brains of double-deficient mice, which also experienced greater weight loss and increased mortality. Deep sequencing revealed no major differences in overall viral genome diversity across diet groups; however, specific mutations, including V330L and D67E in the E gene, and V360I in the NS3 gene, were enriched or detected in nutritionally deficient animals. These findings suggest that antioxidant micronutrient deficiency impairs both humoral and cellular immune responses to ZIKV, potentially facilitating enhanced neuroinvasion. While the functional consequences of the identified mutations warrant further investigation, our results underscore the importance of adequate micronutrient intake for optimal antiviral defense. Further studies are needed to clarify the epidemiological significance of these observations. Full article

The aquaporin 0 (AQP0)/major intrinsic protein of eye lens (MIP) cDNA was cloned and sequenced. Initial studies of the tissue distribution of mRNA expression proved to be incorrect. Subsequent experiments showed that AQP0 mRNA is expressed strongly in the eye with moderately strong expression in the kidneys and some expression was seen in the brain and muscle tissue, and very low expression in the esophagus/fundic stomach. Another set of PCR reactions with five times the amount of cDNA additionally showed mRNA/cDNA expression in the liver, rectal gland, and a very low level in the intestine. Sporadic expression of different pieces of AQP0 cDNA was seen in various experiments in gill and pyloric stomach. A custom polyclonal antibody was produced against a region near the C-terminal end of the AQP0 protein sequence. The antibody gave a band of around the correct size (for the AQP0 protein) on the Western blot, which also showed a few other higher-molecular-weight bands. The antibody was also used in immunohistochemistry, and in the kidney, it showed staining in the proximal II (PII), intermediate segment I (IS I), and late distal tubule (LDT) parts of the sinus zone region of nephrons as well as some staining in the bundle zone tubule segments, suggesting a role for AQP0 as a water channel. In the rectal gland, the antibody showed weak apical membrane staining in a few secretory tubules near the duct, but also somewhat stronger staining in cells appearing to connect various secretory tubules, suggesting a role in cell–cell adhesion. In the spiral valve intestine side wall and valve flap, after signal amplification, weak antibody staining was seen in the apical and lateral membranes of epithelial cells adjacent to the luminal surface. There was also some staining in the intestinal muscle. In the rectum/colon, staining was seen in a layer of cells underlying the epithelium and in some muscle layers. In the gill, there was very weak staining in secondary lamellae epithelial cells and in connective tissue surrounding blood vessels and blood sinuses. The low level of transcript expression in the rectal gland, gill, and intestinal tissues suggests caution in the interpretation of the immunohistochemical staining in these tissues. Full article

Triple-negative breast cancer (TNBC) is an aggressive and clinically challenging subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. This molecular phenotype narrows the availability of targeted therapies and contributes to high rates of early relapse, therapeutic resistance, and poor clinical outcomes. Mounting evidence pinpoints the tumor microenvironment (TME) as a central driver of TNBC progression, immune evasion, and resistance to treatment. The TME encompasses a complex and dynamic network of immune and stromal cells, extracellular matrix components, and soluble mediators that collectively shape tumor behavior and influence therapeutic response. Notably, TNBC often displays an immunologically active microenvironment, marked by high levels of tumor-infiltrating lymphocytes and immune checkpoint expression, opening a window for immune-based therapeutic strategies. This narrative review summarizes current knowledge on the cellular, molecular, and structural features of the TNBC tumor microenvironment, with particular focus on immunosuppressive mechanisms mediated by tumor-associated macrophages, myeloid-derived suppressor cells, cancer-associated fibroblasts, and dysfunctional T cells. We describe the clinical development and therapeutic impact of monoclonal antibodies, including immune checkpoint inhibitors and antibody–drug conjugates. Additionally, we discuss strategies aimed at modulating the TME to enhance monoclonal antibody efficacy, including immune cell reprogramming, extracellular matrix remodeling, cytokine/chemokine blockade, and combination treatment strategies. Finally, we highlight the role of biomarker-driven patient stratification and personalized therapeutic strategies, addressing current challenges and future directions in TME-targeted drug development. Together, these insights underscore the potential of integrating immune modulation and monoclonal antibody-based therapies to improve outcomes for TNBC patients. Full article

Background/Objectives: We aimed to determine safe and immunogenic RSVpreF vaccine dose levels for further clinical development in 2–<18 year olds. Methods: The phase 1, age-descending, open-label Picasso trial evaluated different RSVpreF dose levels in respiratory syncytial virus (RSV)-seropositive 2–<5 year olds and 5–<18 year olds who were either healthy or had chronic medical conditions with increased RSV illness risk. Participants received a single dose of RSVpreF (60 µg or 120 µg dose level). The primary objective was to describe safety and tolerability at each dose level and age group, including frequencies of reactogenicity and adverse events (AEs). The secondary objective was to describe RSV neutralizing antibody responses at each dose level and age group 1 month after vaccination. Results: Overall, 127 participants received RSVpreF 60 µg (2–<5 year olds, n = 20; 5–<18 year olds, n = 35) or 120 µg (n = 24 and n = 48, respectively); 54% were male and 69% were White. Local reactions and systemic events were reported in 17–20% and 33–45% of 2–<5 year olds, respectively, and 49–56% and 52–60% of 5–<18 year olds; most were mild or moderate in severity. AEs were reported in 13–15% of 2–<5 year olds and 8–14% of 5–<18 year olds. No AEs leading to withdrawal or vaccine-related serious AEs were reported. RSV-A and RSV-B neutralizing titer geometric mean fold rises from before to 1 month after vaccination with RSVpreF 60 and 120 µg, which were 17.7–20.6 and 42.8–39.8, respectively, in 2–<5 year olds, and 19.0–23.5 and 20.3–20.3, respectively, in 5–<18 year olds. Conclusions: RSVpreF was safe, well tolerated, and elicited immune responses in RSV-seropositive 2–<18-year-old participants, supporting further clinical development in this pediatric population, including those with chronic conditions. Full article

Arthritis in K/BxN mice is provoked by pathogenic autoantibodies to glucose-6-phosphate isomerase (G6PI), which is a ubiquitously expressed enzyme that is present in cells, in the circulation and on the articular cartilage. When G6PI autoantibodies (auto-Abs) deposit on the articular cartilage of K/BxN mice, arthritis ensues due to the activation of various components of the innate immune system. Recent studies have investigated the in vivo efficacy of recombinant fragment-crystallizable (Fc) protein-based therapeutics. Many of the recombinant Fc proteins that have been evaluated have been shown to have a protective effect in mouse models of arthritis, such as the K/BxN serum-transfer model. More recently, rFc-µTP-L309C, a recombinant human IgG1-Fc with an additional point mutation at position L309C fused to the human IgM tailpiece to form a hexamer, has been shown to ameliorate the arthritis in K/BxN mice. Additional studies have shown that rFc-µTP-L309C has multiple effects that work together to ameliorate the arthritis, including inhibition of neutrophil migration into the joint, inhibition of IL-1β production, downregulation of Th1 and Th17 cells and increases in T regulatory cells and synovial fluid IL-10. In this work, rFc-µTP-L309C was shown to effectively prevent arthritis in the K/BxN serum-transfer model, significantly downregulate inflammatory cytokines/chemokines and ameliorate the arthritis in the endogenous K/BxN model. This amelioration of the arthritis was mediated by a significant decrease in antibody levels. Interestingly, this effect seems to be independent of the neonatal Fc receptor (FcRn). rFc-µTP-L309C was shown to specifically inhibit G6PI autoantibody secretion from B-cells with a concomitant increase in TGFβ and decrease in B-cell activating factor (BAFF). These new findings suggest that rFc-µTP-L309C may provide a therapeutic benefit for other antibody-mediated autoimmune disease through its effects on B-cells. Full article

Kaposi’s Sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV) are oncogenic gammaherpesviruses with high prevalence in sub-Saharan Africa. Both viruses are typically acquired during childhood, establishing lifelong latency. While viral reactivation into the lytic cycle has been mainly studied in adult HIV-infected populations—and more recently in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection—the dynamics of KSHV and EBV infection in children remain poorly understood. Here, we characterize pediatric patients (n = 175; median age 4.6 years; IQR 2.0–8.3) presenting with inflammatory conditions during the COVID-19 pandemic in South Africa (from July 2020 to February 2024). Including a healthy, non-inflammatory control group, we found widespread exposure to SARS-CoV-2 (70.9% seropositivity), with 72.6% of the children being seropositive for EBV and 19.4% for KSHV. There were no significant differences in seroprevalence between children with inflammatory conditions and healthy controls for any of these viruses, although SARS-CoV-2 antibody titers were significantly higher in the inflammatory group, while EBV immune responses were lower in children presenting with inflammation. Among the KSHV-seropositive children, no active viremia was detected (as determined by the absence of viral DNA in the peripheral blood). In contrast, 34.4% of EBV-seropositive children had detectable EBV viral load, with a modestly higher proportion in the inflammatory group. However, EBV viral load levels were comparable between children diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C), Kawasaki Disease (KD), and other inflammatory conditions. Logistic regression analyses revealed that increasing age was significantly associated with higher risk of SARS-CoV-2 and EBV seropositivity, but not KSHV. Notably, the risk of EBV DNA detection in the peripheral blood decreased with age. In summary, this study suggests effective immunological control of gammaherpesvirus infections in HIV-negative paediatric patients, even in the presence of inflammatory conditions that might otherwise trigger viral reactivation. Full article