Search Results (618)

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

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

The precipitation of cryoglobulins, serum immunoglobulins, below 37 °C defines the clinical cryoglobulinemic syndrome, a systemic vasculitis usually characterized by purpura, weakness, and arthralgia. In most cases, this condition is associated with chronic infection by the hepatitis C virus (HCV) and can evolve into B-cell dysregulation and malignancies. The current literature on non-HCV-associated cryoglobulinemia is very limited, and little is known about the immunological and serological profile of affected patients. The cryoglobulinemic syndrome not associated with HCV infection is often found concomitantly with other infections, autoimmune diseases, and B-cell lymphoproliferative disorders. The cryoprecipitation of fibrinogen has been described as a rare disorder, perhaps underestimated and not fully understood, causing thrombotic occlusion and ischemia in different rheumatic disorders. Cold temperature plays a pathogenetic role in autoimmune hemolytic anemias, in which the presence of cold agglutinins produced by B cells at the lymphoplasmacytic cell stage may promote agglutination of red blood cells in the coldest parts of the circulation, even at mild room temperatures, undergoing hemolysis. Laboratory methods for the detection and quantification of cryoproteins are downright critical, and their concurrent detection is pivotal for the diagnosis. In this review, we summarize the clinical involvement of cryoglobulins, cryofibrinogen, and cold agglutinins in non-HCV autoimmune diseases, underlining the crucial steps of the most employed analytic methods. Full article

Chronic inflammatory response syndrome (CIRS) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are debilitating multisystem illnesses that share overlapping symptoms and molecular patterns, including immune dysregulation, mitochondrial impairment, and vascular dysfunction. This review provides a chronological synthesis of biomarker development in CIRS, tracing its evolution from early functional tests such as visual contrast sensitivity (VCS) to advanced transcriptomic profiling. Drawing on peer-reviewed studies spanning two decades, we examine the layered integration of neuroendocrine, immunologic, metabolic, and genomic markers that collectively support a multisystem model of innate immune activation specific to environmentally acquired illness. Particular focus is given to the Gene Expression: Inflammation Explained (GENIE) platform’s use of transcriptomics to classify disease stages and distinguish CIRS from other fatiguing conditions. While ME/CFS research continues to explore overlapping pathophysiologic features, it has yet to establish a unified diagnostic model with validated biomarkers or exposure-linked mechanisms. As a result, many patients labeled with ME/CFS may, in fact, represent unrecognized CIRS cases. This review underscores the importance of structured biomarker timelines in improving differential diagnosis and guiding treatment in complex chronic illness and highlights the reproducibility of the CIRS framework in contrast to the diagnostic ambiguity surrounding ME/CFS. Full article

Background/Objective: Early-onset neonatal sepsis (EOS), defined as infection occurring within the first 72 h after birth, remains a major contributor to neonatal morbidity and mortality worldwide. Although advances in perinatal care have improved overall outcomes, the diagnosis of EOS continues to be challenging. Clinical presentations are often nonspecific, laboratory confirmation is often delayed, and immune responses vary considerably among neonates. Expanding our understanding of the molecular mechanisms underlying EOS is essential in enhancing early detection, refining risk stratification, and guiding therapeutic strategies. This systematic review aims to synthesize the available information on the molecular pathways involved in EOS, focusing on pathogen-induced inflammation, systemic immune responses, sterile inflammatory processes, interactions between infectious and non-infectious pathways, as well as emerging molecular diagnostic approaches. Methods: A comprehensive review of original research articles and reviews published between January 2015 and January 2025 was conducted; studies were included based on their focus on human neonates and their analysis of molecular or immunological mechanisms relevant to EOS pathogenesis, immune dysregulation, or novel diagnostic strategies. Results: Pathogen-driven inflammation typically involves the activation of Toll-like receptors (TLRs), the recruitment of neutrophils, and the release of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, particularly in response to vertical transmission of organisms like Escherichia coli and Streptococcus agalactiae. Systemic inflammatory responses are marked by cytokine dysregulation, contributing to multi-organ dysfunction. Sterile inflammation, often initiated by hypoxia–reperfusion injury or intrauterine stress, amplifies susceptibility to sepsis. Interactions between immune, metabolic, and endothelial pathways further exacerbate tissue injury. Recent advances, including transcriptomic profiling, microRNA-based biomarkers, and immune checkpoint studies, offer promising strategies for earlier diagnosis and individualized therapeutic options. Conclusions: EOS arises from a complex interplay of infectious and sterile inflammatory mechanisms. A deeper molecular understanding holds promise for advancing correct diagnostics and targeted therapies, aiming to improve neonatal outcomes. Full article

Endometriosis is a chronic gynecological pathology marked by the aberrant proliferation of tissue analogous to the endometrial lining outside the uterine cavity. This disorder frequently engenders persistent pelvic discomfort, infertility, and an extensive array of additional manifestations, including menorrhagia, dyspareunia, and gastrointestinal anomalies. Affecting an estimated 10% of women within the reproductive age demographic globally, endometriosis continues to present as a multifaceted and formidable challenge. The precise etiology remains elusive, leading to extended diagnostic intervals and personalized, often inadequate, therapeutic approaches. The intrinsic heterogeneity of endometriosis, evident in its varied phenotypes and clinical manifestations, further complicates both precise diagnosis and efficacious treatment. Conventional management hinges on hormonal interventions, which may not be appropriate for women desiring conception or for those experiencing substantial adverse effects. While surgical procedures are accessible, they do not provide a conclusive resolution, and the probability of recurrence remains high. Progress in diagnostic methodologies, such as non-invasive biomarker analyses, combined with an expanding understanding of the molecular and immunological frameworks that underpin the condition, presents promising prospects for the development of more targeted and individualized non-hormonal treatment modalities in the near future. Full article

Autistic traits—such as social communication deficits, cognitive rigidity, and repetitive behaviors—are increasingly recognized in individuals with schizophrenia, particularly in early-onset cases and subtypes with predominant negative symptoms. This overlap has prompted investigations into shared pathophysiological mechanisms. One emerging area of focus is the role of neuroinflammation in schizophrenia, which may contribute to the manifestation of autistic features. Immunological research indicates the presence of chronic low-grade inflammation, microglial activation, and disruption of the blood–brain barrier in schizophrenia. In particular, an imbalance in T-helper (Th) cell responses—specifically a shift toward Th2 dominance or concurrent Th1/Th2 activation—may lead to dysregulated cytokine production and disturbances in neural function. These findings highlight the importance of exploring immunological pathways as a basis for specific symptom profiles. Additionally, current efforts aim to identify reliable inflammatory biomarkers in schizophrenia that could support diagnosis, predict disease course, and guide treatment. Evaluating neuroinflammatory markers in patients with autistic features may provide novel insight into schizophrenia subtypes and help tailor immunomodulatory therapies. This review explores the expression of autistic traits in schizophrenia and examines the role of neuroinflammation and Th1/Th2 imbalance as potential mechanisms and biomarkers. Full article

Background/Objectives: Microhematuria is common in patients with infective endocarditis (IE). The present study aims to assess whether the addition of microhematuria in the 2023 Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) minor immunological criteria could enhance its diagnostic performance. Methods: This retrospective study was conducted at the Lausanne University Hospital, Switzerland (2014–2024). All patients with suspected IE and urinalysis within 24 h from presentation were included. The Endocarditis Team classified episodes as IE or non-IE. Microhematuria was defined as >5 red blood cells per high power field (HPF). Results: Among 801 episodes with suspected IE, 263 (33%) were diagnosed with IE. Microhematuria (>5/HPF) was present in 462 (58%) episodes, with no difference between episodes with and without confirmed IE (61% versus 56%; p = 0.223). Based on the 2023 ISCVID-Duke, minor immunological criteria were present in 42 episodes (5%). By adding microhematuria, 473 (59%) episodes met the minor immunological criteria. Sensitivity of the clinical criteria of the 2023 ISCVID-Duke version without and with hematuria was calculated at 75% (69–80%) and 86% (81–90%), respectively. Specificity was at 52% (48–57%) and 40% (36–45%), respectively. Among episodes with suspected IE, microhematuria was associated with female sex, enterococcal bacteremia, sepsis or septic shock, acute kidney injury, non-cerebral embolic events, and bone and joint infection. Conclusions: Microhematuria was frequent among patients with suspected IE, but it was not associated with the diagnosis of IE. The addition of microhematuria in the 2023 ISCVID-Duke minor immunological criteria did not enhance the overall performance of the criteria. Full article

Background/Objectives: Osteopontin (OPN) is a 34 kDa protein that is extensively phosphorylated and rich in aspartic acid, produced by a single-copy gene, and altered by post-translational processes. In several diseases, OPN has been discovered to play a direct role in immunological and inflammatory responses. It is also important in kidney stone disease, preeclampsia, cardiovascular disease, endometriosis, and cancer, among other pathological conditions. It is a crucial extracellular matrix molecule involved in oncology, due to its ability to bridge the gap between inflammation and carcinogenesis. Methods: Our systematic review has as PICO “Does Osteopontin have possible etiological and prognostic correlations in patients affected by endometrial carcinoma?” Based on online data collected from PubMed, Scholar, Embase, Scopus, and other sources, a preliminary analysis was conducted. A keyword search for “Osteopontin” AND “tumors”, “endometrial cancer”, and other related terms was used to identify the publications. The relevance of scientific research was used to select articles in English. Results: For our systematic review, the citation search yielded nine articles on the topic. At the endometrial level, OPN plays a role in a variety of biological processes, including angiogenesis, metastasis, altered tissue remodeling, immunological responses, cell adhesion, and migration. Conclusions: With established direct correlations and a potential role in the assessment of the diagnosis and prognosis of the disease, OPN participates in endometrial cancer, drawing more and more attention from researchers. Full article

Background: Herpes zoster (HZ), resulting from the reactivation of latent varicella-zoster virus, has been increasingly observed in individuals following COVID-19. Given the shared immunological disturbances between the two conditions, this study aimed to investigate whether HZ following COVID-19 is associated with an elevated risk of renal, infectious, and autoimmune complications. Methods: This retrospective cohort study utilized data from the TriNetX global federated health network, encompassing over 9 million adults diagnosed with COVID-19 between January 2020 and January 2022. Patients who developed HZ within one year following COVID-19 diagnosis were compared to 1:1 propensity score-matched controls without HZ. Time-to-event analyses over a three-year follow-up period were conducted to estimate the risks of major adverse kidney events (MAKE; defined as acute kidney injury, dialysis dependence, or severely reduced kidney function with eGFR <30 mL/min/1.73 m²), sepsis, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), using Kaplan–Meier survival curves and Cox proportional hazards models. Results: HZ following COVID-19 was significantly associated with increased risks of all four outcomes: MAKE (HR 1.940, 95% CI: 1.866–2.017), sepsis (HR 2.362, 95% CI: 2.250–2.479), SLE (HR 2.667, 95% CI: 2.254–3.156), and RA (HR 2.484, 95% CI: 2.267–2.730). Subgroup analyses identified older age, diabetes, impaired renal function, and elevated inflammatory markers as key risk-enhancing factors. Conclusions: HZ following COVID-19 may serve as a clinical indicator of systemic immune dysregulation and is independently associated with increased long-term risks of renal, infectious, and autoimmune sequelae. Enhanced monitoring of this high-risk population is warranted. Full article

Systemic autoimmune rheumatic diseases (SARDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SS), are traditionally characterized by chronic inflammation and immune-mediated damage to joints and other tissues. However, many patients also experience symptoms such as widespread pain, persistent fatigue, cognitive dysfunction, and autonomic disturbances that cannot be attributed directly or entirely to peripheral inflammation or structural pathology. These conditions suggest the involvement of interactions between the nervous and immune systems, which probably include both peripheral and central components. This review summarizes the current knowledge of neurological and neuroimmune mechanisms that may contribute to these symptoms in SARDs. Glial cell activation and neuroinflammation within the central nervous system (CNS), small-fiber neuropathy (SFN) affecting peripheral nociceptive pathways, central pain sensitization, and autonomic nervous system dysfunction will be discussed. In addition, the role of molecular mediators, including cytokines, neuropeptides, and microRNAs, that could potentially modulate neuroimmune signaling will be highlighted. Integrating findings from pathology, immunology, and neuroscience, this review seeks to provide a useful framework for understanding neuroimmune dysregulation in SARDs. It also highlights the clinical relevance of these mechanisms and summarizes new directions for diagnosis and treatment. Full article

Background and Objectives: Pediatric Sjögren’s syndrome is a rare autoimmune disease with a heterogeneous clinical expression and limited pediatric-specific diagnostic criteria. Ocular involvement often represents an early manifestation, yet it may go unrecognized in children due to poor symptom reporting and the underuse of objective diagnostic tools. This retrospective study evaluated six pediatric patients with Sjögren’s syndrome, integrating systemic and ocular findings with a focus on early immunological and clinical markers. Materials and Methods: All patients underwent ophthalmological assessments, including tear break-up time, Schirmer’s test, and slit-lamp examination. Results: Tear break-up time values consistently indicated tear film instability (mean RE 7.4 ± 2.5 s; LE 7.7 ± 2.3 s), while Schirmer’s test showed greater variability. Slit-lamp examination revealed inhomogeneous tear films in all patients and blepharitis in 66.7%, consistent with Meibomian gland dysfunction. Systemic features included arthralgia, Raynaud’s phenomenon, fatigue, and frequent seropositivity for ANA and anti-SSA/Ro antibodies. Minor salivary gland biopsy confirmed lymphoepithelial sialadenitis in all cases. Conclusions: These findings highlight the importance of combining laboratory and clinical markers with ophthalmological parameters to support an early diagnosis of Sjögren’s syndrome in pediatric patients. Integrating TBUT and slit-lamp evaluation with serological and histopathological data may enhance diagnostic accuracy and guide timely, targeted intervention to prevent long-term complications. Full article

Background/Objectives: Coeliac disease is an immune-mediated disorder of the gastrointestinal tract that may result in significant nutritional deficiencies. Effective management requires strict, lifelong adherence to a gluten-free diet. Both underdiagnosis and unnecessary dietary restrictions can adversely affect patients’ health and quality of life. To assess adherence to the current recommendations for the laboratory diagnosis of coeliac disease and promote evidence-based practices while reducing inter-laboratory variability, the Spanish Group on Autoimmunity of the Spanish Society of Immunology conducted a nationwide survey. Methods: A thirty-item survey was distributed to fifty autoimmune laboratories across Spain. Data were collected through a structured Excel-based questionnaire comprising multiple-choice items, which was distributed via email to the participating laboratories. It explored practices related to the diagnosis of coeliac disease in the general population and among at-risk groups as well as approaches to patient follow-up and demand management. Results: Thirty-five laboratories completed the electronic questionnaire. For the serological screening of coeliac disease, all the respondents reported using IgA anti-tissue transglutaminase (tTG-IgA) antibody testing together with total IgA measurement to assess IgA competence. However, consistent use of anti-endomysial antibody testing and HLA genotyping and adherence to pre-analytical recommendations for accurate interpretation of results were not uniform across centres. Conclusions: At the time these data were collected (the third trimester of 2021), the 2020 ESPGHAN guidelines for the diagnosis of coeliac disease in the paediatric population had not yet been fully implemented in most of the laboratories surveyed. For diagnosing adults, most laboratories adhered to local and European guidelines. Full article

Infective endocarditis (IE) during pregnancy, while uncommon, is associated with substantial maternal and fetal morbidity and mortality due to the complex physiological adaptations of pregnancy. Hemodynamic alterations, including increased cardiac output and changes in vascular resistance, combined with immunological modulation, predispose pregnant individuals to increased risk of infection and associated complications. Predominant pathogens implicated in pregnancy-associated IE are Staphylococcus aureus, Streptococcus viridans, and Enterococcus faecalis, with S. aureus infections frequently leading to poorer clinical outcomes. Diagnosis remains challenging due to commonly atypical presentation and relies on microbiological identification via blood cultures in conjunction with imaging modalities such as transthoracic echocardiography. IE in pregnancy is associated with increased maternal mortality rates (5–17%) and adverse fetal outcomes, including preterm birth, intrauterine growth restriction (IUGR), and fetal loss. Management necessitates careful selection of antimicrobial therapy to ensure efficacy while minimizing fetal toxicity, especially in settings of increased antimicrobial resistance. Anticoagulation and surgical interventions must be judiciously considered, with surgical timing individualized based on the severity of heart failure and coordinated multidisciplinary care. In conclusion, IE during pregnancy constitutes a significant clinical challenge, underscoring the need for enhanced diagnostic strategies, optimized therapeutic protocols, and the development of pregnancy-specific management guidelines to improve maternal and fetal outcomes. Full article