Search Results (8,071)

Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy would be important. Methods: We evaluated the clinical efficacy of tumor resection (TR) after chemotherapy or anti-PD-1 therapy in patients with unresectable advanced or recurrent G/GEJ cancer and analyzed the immune status of tumor microenvironment (TME) by immunohistochemistry using their surgically resected specimens. Results: Patients treated with TR after anti-PD-1 therapy had significantly longer survival compared to those treated with chemotherapy and anti-PD-1 therapy alone. Expression of human leukocyte antigen (HLA) class I and major histocompatibility complex (MHC) class II on tumor cells was markedly downregulated after anti-PD-1 therapy compared to chemotherapy. Furthermore, the downregulation of HLA class I may be associated with the activation of transforming growth factor-β signaling pathway in the TME. Conclusions: Immune escape from cytotoxic T lymphocytes may be induced in the TME in patients with unresectable advanced or recurrent G/GEJ cancer after anti-PD-1 therapy due to the downregulation of HLA class I and MHC class II expression on tumor cells. TR may be a promising treatment strategy for these patients when TR is feasible after anti-PD-1 therapy. Full article

This study examined the distribution and disease associations of non-HLA-B*27 HLA-B alleles in Romanian spondyloarthritis (SpA) patients, aiming to address the underrepresentation of Eastern European populations in immunogenetic research. Methods: We analyzed 263 HLA-B*27-negative patients from Northeastern Romania fulfilling ASAS criteria. HLA-B genotyping was performed at two-digit resolution, and allele distributions were compared with two Romanian HLA-B*27-negative control groups (n = 335 and n = 1705 cases), using chi-square testing and logistic regression. Compared to controls, HLA-B*47 (p = 0.0007) and HLA-B*54 (p = 0.0013) were significantly enriched, while HLA-B*40 was underrepresented (p = 0.0287). Notably, HLA-B*54 was observed exclusively in axial SpA. Within the cohort, both HLA-B*13 and HLA-B*57 alleles were associated with psoriasis, while HLA-B*37 and HLA-B*41 alleles were clustered within the reactive arthritis group. The HLA-B*35 and HLA-B*18 alleles were the most frequently observed alleles across most clinical phenotypes. When comparing the frequency of HLA-B associations, the most common genotypes among SpA patients were B*08-B*18, B*13-B*35, and B*35-B*51. Notably, B*08-B*18 was more frequent in patients with radiographic sacroiliitis grade ≥ 2, while B*35-B*51 was more frequent in those with confirmed systemic inflammation, as indicated by elevated CRP or ESR levels. Analysis of peptide-binding patterns revealed a cluster of risk alleles, HLA-B*08, B*18, B*35, B*40, and B*54, sharing similar features, distinct from the canonical profile of B*27. These findings highlight the contribution of non-B*27 HLA-B alleles to SpA susceptibility in an Eastern European population and support the notion that HLA-B*27-negative SpA may represent a distinct clinical and immunological entity, driven by alternative pathogenic mechanisms. They also emphasize the importance of population-specific immunogenetic profiling and support expanding genetic characterization in HLA-B*27-negative patients. Full article

Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative agents of endometriosis, and highlight implications in the general population and clinical work. A thorough review of experimental, epidemiologic, and mechanistic research studies was conducted to explain the association between EDCs and endometriosis. Among the primary EDCs under investigation are polychlorinated biphenyls, dioxins, phthalates, and bisphenol A (BPA). Despite methodological heterogeneity and some discrepancies, epidemiologic evidence supports a positive association between some increased levels of BPA, phthalates, and dioxins in urine or in blood, and endometriosis. Experiments support some effect of EDCs on endometrial cells and causing endometriosis. EDCs function as xenoestrogens, alter immune function, induce oxidative stress, and disrupt progesterone signaling. Epigenetic reprogramming may play a role in mediating EDC-induced endometriosis. Endocrine, immunological, and epigenetic pathways link EDCs and endometriosis. Prevention techniques require deeper comprehension of those factors. Causal linkages and possible treatment targets should be based on longitudinal studies and multi-omics techniques. Restriction of EDCs could be beneficial for endometriosis prevalence limitation. Full article

Macrophages are undoubtedly one of the most widely studied cells of the immune system, among other reasons, because they are involved in a wide variety of biological processes. Deregulation of their activity is observed in a number of different disorders, including autoimmune diseases. At the same time, mammalian target of rapamycin (mTOR) is attracting increasing research attention because the pathways dependent on this kinase are activated by a variety of signals, including cytokines and proinflammatory mediators, mediate essential processes for cell survival and metabolism, and can be regulated epigenetically via microRNAs. Therefore, our narrative review aimed to summarize and discuss recent advances in the knowledge of the activation of mTOR signaling in macrophages, with a special focus on autoimmune disorders and the possibility of mTOR control by microRNAs. The summarized research observations allowed us to conclude that the effects of activity and/or inhibition of individual mTOR complexes in macrophages are largely context dependent, and therefore, these broad immunological contexts and other specific conditions should always be taken into account when attempting to modulate these pathways for therapeutic purposes. Full article

Background: HIV-associated neurocognitive disorders (HANDs) continue to be a significant concern, despite the advancements in prognosis achieved through Combination Antiretroviral Therapy (cART). Neuropsychological assessment, recommended by international guidelines for HANDs diagnosis, can be resource-intensive. Brief screening tools, like the International HIV Dementia Scale (IHDS) and the Montreal Cognitive Assessment (MoCA), are crucial in facilitating initial evaluations. This study aims to assess the Italian IHDS (IHDS-IT) and evaluate its sensitivity and specificity in detecting cognitive impairment in HIV patients. Methods: This cross-sectional study involved 294 patients aged ≥30 years, evaluated at the Immunology Unit of the University of Cagliari. Cognitive function was assessed using the MoCA and IHDS. Laboratory parameters, such as CD4 nadir, current CD4 count, and HIV-RNA levels, were also collected. Statistical analyses included Spearman’s correlation, Receiver Operating Characteristic analysis, and the Youden J statistic to identify the optimal IHDS-IT cut-off for cognitive impairment detection. Results: The IHDS and MoCA scores showed a moderate positive correlation (Spearman’s rho = 0.411, p < 0.0001). ROC analysis identified an IHDS-IT cut-off of ≤9, yielding an Area Under the Curve (AUC) of 0.76, sensitivity of 71.7%, and specificity of 67.2%. At this threshold, 73.1% of patients with MoCA scores below 23 also presented abnormal IHDS scores, highlighting the complementary utility of both cognitive assessment instruments. Conclusions: The IHDS-IT exhibited fair diagnostic accuracy for intercepting cognitive impairment, with a lower optimal cut-off than previously reported. The observed differences may reflect this study cohort’s demographic and clinical characteristics, including advanced age and long-lasting HIV infection. Further, longitudinal studies are necessary to validate these findings and to confirm the proposed IHDS cut-off over extended periods. Full article

The prostate gland, a male accessory reproductive organ, is regulated by hormonal inputs and autonomic innervation from the major pelvic ganglion. This study examined the effects of major pelvic ganglion denervation on prostate histology, immune cell infiltration, and systemic levels of prolactin, testosterone, and cytokines in rats. Male Wistar rats (300–350 g) were divided into groups receiving bilateral axotomy of the hypogastric nerve, the pelvic nerve, or both, alongside with a sham-operated control. After 15 days, the animals were killed, and prostate tissue was dissociated in DMEM medium containing DNase I and collagenase. The dissociated cells were stained with fluorochrome-conjugated antibodies, and cell characterization was performed using a flow cytometer. Hematoxylin and eosin (H&E) staining was used to analyze histological characteristics, while testosterone, prolactin, and interleukin levels were measured via ELISA. Histological analysis revealed inflammatory atypical hypertrophy e hiperplasia. Immunological assessments demonstrated increased leukocytes, T lymphocytes (CD4⁺ and CD8⁺), B lymphocytes, and macrophages following double nerve axotomy. Serum analyses showed elevated pro-inflammatory cytokines IL-1β, IL-6, and IFN-γ, as well as anti-inflammatory IL-10, in denervated animals. Hormonal assessments revealed significant increases in serum prolactin and testosterone levels after double axotomy. Loss of neural control may promote pathological prostate changes via inflammation and hormonal dysregulation, offering insights into neuroimmune and neuroendocrine mechanisms underlying prostate pathologies. Full article

Chronic low-grade inflammation is a hallmark of both metabolic and neurodegenerative diseases. In recent years, several studies have highlighted the pivotal role of systemic metabolic dysfunction, particularly insulin resistance, in shaping neuroinflammatory processes and contributing to impaired cognitive performance. Among metabolic disorders, type 2 diabetes mellitus has emerged as a major risk factor for the development of age-related neurodegenerative conditions, suggesting a complex and bidirectional crosstalk between peripheral metabolic imbalance and central nervous system function. This review aims to explore the cellular and molecular mechanisms underlying the interaction between metabolic dysregulation and brain inflammation. By integrating current findings from endocrinology, immunology, and neuroscience, this work provides a comprehensive overview of how chronic metabolic inflammation may contribute to the onset and progression of neurodegenerative conditions. This interdisciplinary approach could offer novel insights into potential therapeutic strategies targeting both metabolic and neuroinflammatory pathways. Full article

Oncology physiotherapists frequently provide care for patients experiencing severe immunosuppression. Exercise immunology, the science that studies the effects of exercise on the immune system, is a rapidly evolving field with direct relevance to oncology physiotherapists. Understanding oncology physiotherapists’ perspectives on the subject of immune functioning is essential to explore its possible integration into clinical reasoning. This study aimed to assess the perspectives of oncology physiotherapists concerning immune functioning in oncology physiotherapy. For this qualitative research, semi-structured interviews were performed with Dutch oncology physiotherapists. Results were analyzed via inductive thematic analysis, followed by a validation step with participants. Fifteen interviews were performed. Participants’ ages ranged from 30 to 63 years. Emerging themes were (1) the construct ‘immune functioning’ (definition, and associations with this construct in oncology physiotherapy), (2) characteristics related to decreased immune functioning (in oncology physiotherapy), (3) negative and positive influences on immune functioning (in oncology physiotherapy), (4) tailored physiotherapy treatment, (5) treatment outcomes in oncology physiotherapy, (6) the oncology physiotherapist within cancer care, and (7) measurement and interpretation of immune functioning. In conclusion, oncology physiotherapists play an important role in the personalized and comprehensive care of patients with cancer. They are eager to learn more about immune functioning with the goal of better informing patients about the health effects of exercise and to tailor their training better. Future exercise-immunology research should clarify the effects of different exercise modalities on immune functioning, and how physiotherapists could evaluate these effects. Full article

Multiple sclerosis (MS) and allergic diseases, traditionally considered immunologically opposing entities, may share pathogenic mechanisms rooted in immune dysregulation. While MS is predominantly mediated by Th1 and Th17 responses and allergies by Th2 responses, emerging evidence suggests overlapping immunological pathways, including the involvement of histamine, regulatory T cells, and innate lymphoid cells. This review synthesizes current knowledge on the epidemiological and immunopathological associations between MS and allergies. Epidemiological studies have yielded inconsistent results, with some suggesting a protective role for respiratory and food allergies against MS onset, while others find no significant correlation. Clinical studies indicate that food allergies in adults may be associated with increased MS inflammatory activity, whereas childhood atopy might exert a protective effect. In addition, we review hypersensitivity reactions to disease-modifying treatments for MS, detailing their immunological mechanisms, clinical presentation, and management, including desensitization protocols where applicable. Finally, we explore how treatments for allergic diseases—such as clemastine, allergen immunotherapy, montelukast, and omalizumab—may modulate MS pathophysiology, offering potential therapeutic synergies. Understanding the interplay between allergic and autoimmune processes is critical for optimizing care and developing innovative treatment approaches in MS. Full article

Background/Objectives: Actinobacteria are one of the largest bacterial phyla. These microbes produce bioactive compounds, such as antifungals, antibiotics, immunological modulators, and anti-tumor agents. Studies on actinobacteria isolated from the Brazilian Savannah biome (Cerrado) are scarce and mostly address metagenomics or the search for hydrolytic enzyme-producing microbes. Solanum lycocarpum (lobeira) is a tree widely employed in regional gastronomy and pharmacopeia in Central Brazil. Methods: In this work, 60 actinobacteria isolates were purified from the rhizosphere of S. lycocarpum. Eight Streptomyces spp. isolates were selected for in vitro antifungal activity against Cryptococcus neoformans H99, the C. neoformans 89-610 fluconazole-tolerant strain, C. gattii NIH198, Candida albicans, C. glabrata, and C. parapsilosis. The ability of the aqueous extracts of the isolates to induce the in vitro secretion of tumor necrosis factor (TNF-α), nitric oxide (NO), interleukin-6 (IL-6), and IL-10 by murine macrophages was also evaluated. Results: All extracts showed antifungal activity against at least two yeast species. Streptomyces spp. LAP11, LDB2, and LDB17 inhibited C. neoformans growth by 40–93%. Most extracts (except LAP2) also inhibited C. gattii. None inhibited C. albicans, but all inhibited C. glabrata (40–90%). Streptomyces sp. LAP8 extract increased nitric oxide production by approximately 347-fold in murine macrophages, while LDB11 extract suppressed LPS-induced TNF-α production by 70% and simultaneously increased IL-10 secretion, suggesting immunosuppressive potential. Conclusions: The results revealed that Cerrado actinobacteria-derived aqueous extracts are potential sources of antifungal and immunomodulatory biocompounds. Full article

Chronic nasopharyngeal and otic disorders in children represent a significant clinical challenge due to their multifactorial etiology, variable presentation, and frequent resistance to standard therapies. Although often approached from a symptomatic or anatomical perspective, these conditions are deeply rooted in histological and molecular alterations that sustain inflammation, impair mucosal function, and promote recurrence. This narrative review synthesizes the current knowledge on the normal histology of the nasopharynx, Eustachian tube, and middle ear, and explores key pathophysiological mechanisms, including epithelial remodeling, immune cell infiltration, cytokine imbalance, and tissue fibrosis. Special emphasis is placed on the role of immunohistochemistry in defining inflammatory phenotypes, barrier dysfunction, and remodeling pathways. The presence of biofilm, epithelial plasticity, and dysregulated cytokine signaling are also discussed as contributors to disease chronicity. These findings have direct implications for diagnosis, therapeutic stratification, and postoperative monitoring. By integrating histological, immunological, and molecular data, clinicians can better characterize disease subtypes, anticipate treatment outcomes, and move toward a more personalized and biologically informed model of pediatric ENT care. Full article

Secukinumab (SEC) is a recombinant, fully human monoclonal antibody that is selective for interleukin-17A (IL-17A). SEC may increase the risk of developing infections such as oral herpes and oral candidiasis. The aim of this case report and literature review was to describe chronic hyperplastic candidiasis (CHC) in a patient with psoriasis (PsO) and psoriatic arthritis (PsA) treated with SEC. CHC is a rare and atypical clinical entity. A definitive diagnosis requires biopsy of the oral mucosa for histopathological diagnosis (PHD). The differential diagnosis includes hairy tongue, hairy leukoplakia, oral lichen planus (OLP), oral lichenoid reaction (OLR), leukoplakia, frictional keratosis, morsication, oral psoriasis, syphilis, and oral lesions associated with coronavirus disease (COVID-19). In addition to the usual factors (xerostomia, smoking, antibiotics, vitamin deficiency, immunosuppression, comorbidities), the new biological therapies/immunotherapies are a predisposing factor for oral candidiasis. The therapeutic approach must be multidisciplinary and in consultation with a clinical immunologist. Dentists and specialists (oral medicine, dermatologists, rheumatologists) must be familiar with the oral adverse events of the new biological therapies. Simultaneous monitoring of patients by clinical immunology and oral medicine specialists is crucial for timely diagnosis and therapeutic intervention to avoid possible adverse events and improve quality of life (QoL). Full article

Background/Objectives: While ART effectively suppresses HIV viremia, many PLWH exhibit persistent immune dysfunction. This study aimed to assess immune recovery and immune exhaustion (PD-1/PD-L1 expression) in newly diagnosed versus long-term ART-treated individuals. Methods: We analyzed 79 PLWH: 52 newly diagnosed individuals (12-month follow-up) and 27 long-term-treated patients (Ukrainian refugees). Flow cytometry was used to evaluate CD4+ and CD8+ counts, the CD4+/CD8+ ratio, and PD-1/PD-L1 expression on CD3+, CD4+, and CD19+ lymphocytes. ART regimen and HIV subtype were included as covariates in linear regression models. Results: At 12 months, CD4+ counts were similar between groups (median 596.5 vs. 621 cells/μL, p = 0.22), but newly diagnosed patients had higher CD8+ counts (872 vs. 620 cells/μL, p = 0.028) and a lower CD4+/CD8+ ratio (0.57 vs. 1.05, p = 0.0027). Immune exhaustion markers were significantly elevated in newly diagnosed individuals: CD4+ PD-1+ T cells (24.4% vs. 3.85%, p = 0.0002) and CD3+ PD-1+ T cells (27.3% vs. 12.35%, p < 0.0001). Linear regression confirmed group membership independently predicted higher CD3+ (β = +21.92, p < 0.001), CD4+ (β = +28.87, p < 0.0001), and CD19+ (β = +8.73, p = 0.002) percentages. Lipid parameters and SCORE2 did not differ significantly. Conclusions: Despite virologic suppression and CD4+ recovery, immune exhaustion markers remain elevated in newly diagnosed PLWH, suggesting incomplete immune normalization. Traditional parameters (CD4+ count and CD4+/CD8+ ratio) may not fully capture immune status, warranting broader immunologic profiling in HIV care. Full article

Influenza B viruses, divided into B/Victoria and B/Yamagata lineages, have not had B/Yamagata isolates after 2020. A study evaluated immunity to influenza B surface antigens hemagglutinin (HA) and neuraminidase (NA) in 138 patient sera from 2023 and 23 pairs of sera from 2018 to 2019 vaccine recipients. The phylogenetic tree of the influenza B virus, based on HA and NA genes, shows that the Yamagata lineage evolves gradually, while the Victoria lineage exhibits rapid mutations with short branches. In 2023, mean levels of antibodies to HA and NA of B/Yamagata virus were higher than to B/Victoria, despite no cases of B/Yamagata lineage isolation after 2020. The titers of antibodies to NA of B/Yamagata statistically significantly differed among individuals born before and after 1988. Among patients examined in 2018–2019, neuraminidase-inhibiting (NI) antibody titers before vaccination were higher to B/Yamagata than to B/Victoria, and NI antibodies to B/Victoria and B/Yamagata positively correlated with neutralizing antibodies to B/Victoria virus before and after vaccination. Immunity to B/Yamagata virus was stronger in 2023, despite no isolation since 2020, probably due to the presence of cross-reactive antibodies from B/Victoria infections or vaccinations. Antibodies to NA of B/Victoria and B/Yamagata in 2023 correlated significantly in patients born before 1988, potentially supporting the concept of ‘antigenic sin’ phenomenon for influenza B viruses. The fact that NI antibody titers to B/Victoria and B/Yamagata correlated with neutralizing antibody titers to B/Victoria may suggest broad cross-protection. Studying influenza B virus NA antigenic properties helps understand the evolution and antigenic competition of HA and NA. Full article

Allergic contact dermatitis (ACD) is an immunologic reaction to a dermal chemical exposure that, once triggered in an individual, will result in an allergic response following subsequent encounters with the allergen. Air Force epidemiological consultations have indicated that aircraft structural maintenance workers may experience ACD at elevated rates compared to other occupations. We aimed to better understand the utility of non-animal testing methods in characterizing the sensitization potential of chemicals used during Air Force operations by evaluating the skin sensitization hazard of Air Force-relevant chemicals using new approach methodologies (NAMs) in a case study. We also evaluated the use of NAM data to develop preliminary candidate surface guidelines (PCSGs, maximum concentrations of chemicals on workplace surfaces to prevent induction of dermal sensitization) for chemicals identified as sensitizers. NAMs for assessing skin sensitization, including in silico models and experimental assays, were leveraged into an integrated approach to predict sensitization hazard for 19 chemicals. Local lymph node assay effective concentration values were predicted from NAM assay data via previously published quantitative models. The derived values were used to calculate PCSGs, which can be used to compare the presence of these chemicals on work surfaces to better understand the risk of Airmen developing ACD from occupational exposures. Full article