Immunological Mechanisms Research Articles

Safety and efficacy of tofacitinib in 97 alopecia areata patients.

Alopecia areata (AA) is a recurrent immune-mediated disorder causing hair loss without any scarring being present. It affects hairs on the head or other parts of the body and can occur at any age and in both genders. It seems that AA is associated with a higher rate of psychological disorders resulting from hair loss and the esthetic and social repercussions of it. Common treatments like corticosteroids do not work for every patient and recent treatment options focusing on the immunologic mechanisms like tofacitinib have shown some promising results. It's a retrospective study on patients with AA, AT, AU taking oral tofacitinib as a treatment for at least 6 months. Scalp hair loss was assessed before treatment and at each visit using the Severity of Alopecia Tool (SALT) score. Of 97 cases, 69.1% demonstrated over 50% SALT score improvement, with 44.3% having 90% or more decrease in SALT score. Patients who suffered from patchy AA were more responsive compared to patients with AT and AU subtypes and had a greater percent change in SALT score. Tofacitinib was tolerated quite well and no significant adverse events were reported. Tofacitinib should be taken into consideration as an efficacious treatment option for patients with AA, AT and AU.

Advanced Immunomodulatory Biomaterials for Therapeutic Applications.

The multifaceted biological defense system modulating complex immune responses against pathogens and foreign materials plays a critical role in tissue homeostasis and disease progression. Recently developed biomaterials that could specifically regulate immune responses, nanoparticles, graphene, and functional hydrogels have contributed to the advancement of tissue engineering as well as disease treatment. The interaction between innate and adaptive immunity, collectively determining immune responses, can be regulated by mechanobiological recognition and adaptation of immune cells to the extracellular microenvironment. Therefore, applying immunomodulation to tissue regeneration and cancer therapy involves manipulating the properties of biomaterials by tailoring their composition in the context of the immune system. In this review, we provide a comprehensive overview of how the physicochemical attributes of biomaterials determine immune responses, focusing on the physical properties that influence innate and adaptive immunity. This review also underscores the critical aspect of biomaterial-based immune engineering for the development of novel therapeutics and emphasizes the importance of understanding the biomaterials-mediated immunological mechanisms and their role in modulating the immune system. This article is protected by copyright. All rights reserved.

The Importance of HHLA2 in Solid Tumors—A Review of the Literature

Cancer immunotherapy is a rapidly developing field of medicine that aims to use the host’s immune mechanisms to inhibit and eliminate cancer cells. Antibodies targeting CTLA-4, PD-1, and its ligand PD-L1 are used in various cancer therapies. However, the most thoroughly researched pathway targeting PD-1/PD-L1 has many limitations, and multiple malignancies resist its effects. Human endogenous retrovirus-H Long repeat-associating 2 (HHLA2, known as B7H5/B7H7/B7y) is the youngest known molecule from the B7 family. HHLA2/TMIGD2/KIRD3DL3 is one of the critical pathways in modulating the immune response. Recent studies have demonstrated that HHLA2 has a double effect in modulating the immune system. The connection of HHLA2 with TMIGD2 induces T cell growth and cytokine production via an AKT-dependent signaling cascade. On the other hand, the binding of HHLA2 and KIR3DL3 leads to the inhibition of T cells and mediates tumor resistance against NK cells. This review aimed to summarize novel information about HHLA2, focusing on immunological mechanisms and clinical features of the HHLA2/KIR3DL3/TMIGD2 pathway in the context of potential strategies for malignancy treatment.

The Potential Impact of the Gut Microbiota on Neonatal Brain Development and Adverse Health Outcomes

Over the past decade, microbiome research has significantly expanded in both scope and volume, leading to the development of new models and treatments targeting the gut–brain axis to mitigate the effects of various disorders. Related research suggests that interventions during the critical period from birth to three years old may yield the greatest benefits. Investigating the substantial link between the gut and brain during this crucial developmental phase raises fundamental issues about the role of microorganisms in human health and brain development. This underscores the importance of focusing on the prevention rather than the treatment of neurodevelopmental and neuropsychiatric disorders. The present review examines the gut microbiota from birth to age 3, with a particular focus on its potential relationship with neurodevelopment. This review emphasizes the immunological mechanisms underlying this relationship. Additionally, the study investigates the impact of the microbiome on cognitive development and neurobehavioral issues such as anxiety and autism. Importantly, it highlights the need to integrate mechanistic studies of animal models with epidemiological research across diverse cultures to better understand the role of a healthy microbiome in early life and the implications of dysbiosis. Furthermore, this review summarizes factors contributing to the transmission of gut microbiome-targeted therapies and their effects on neurodevelopment. Recent studies on environmental toxins known to impact neurodevelopment are also reviewed, exploring whether the microbiota may mitigate or modulate these effects.

Abstract PO1-02-01: T Cell Receptor Sequencing to Monitor Pelareorep-Induced Expansion of Tumor Infiltrating Lymphocytes

Abstract Background: Tumor infiltrating lymphocytes (TILs) represent a major immunological tumor control mechanism that is associated with better prognosis in breast cancer. We have previously reported the effect of pelareorep (pela), an intravenously delivered, non-engineered oncolytic reovirus, on a composite measurement of TILs and tumor cellularity (CelTIL) from the AWARE-1 window-of-opportunity study in patients with early breast cancer (eBC). These results showed treatment increased in CelTIL scores especially in the atezolizumab group. To confirm and extend these findings we applied T cell receptor sequencing of matched tumor tissue and whole blood pre and post-treatment from the AWARE-1 study to further explore the effects of pela therapy on TILs. Methods: Newly diagnosed HR+/HER2- eBC patients were enrolled into two cohorts: Cohort 1: pela + letrozole (n=10); and Cohort 2: pela + letrozole + atezolizumab (n=10). Pela was administered on days 1, 2 and 8, 9, and atezolizumab was given on day 3. Tumor biopsies (FFPE samples) collected pre-treatment (~D-23) and on day ~21 when tumors were surgically removed. T cell fraction analysis and T cell receptor sequencing were performed by Adaptive Biotechnology (Seattle, Washington) Immunoseq protocol. Results: As was shown for the CelTIL scores, an increase in the tumor T cell fraction, a direct measurement of TILs, was observed at 1-month post-treatment in both cohorts with a mean percent increase of 21% for Cohort 1 and 67% for Cohort 2. Through TCR-sequencing of tumor tissue, we identified TIL clones and tracked their differential abundance in tumor tissue and blood post-treatment. The results of this analysis at Day 21 showed a mean post-treatment expansion of 10 tumor specific clones in the blood for Cohort 1, and a mean post-treatment increase of 40 tumor specific clones for Cohort 2. Conclusions: These results confirm the previously reported CelTIL results from AWARE-1 on pela-induced increases in TILs and demonstrate the expansion of these clones in both tumor and blood as a consequence of pela therapy for HR+/HER2- breast cancer. Citation Format: Richard Trauger, Houra Loghmani, Matt Coffey, Fernando Salvador, Joaquín Gavilá, Luis Manso, Tomás Pascual, Aleix Prat, Thomas Heineman. T Cell Receptor Sequencing to Monitor Pelareorep-Induced Expansion of Tumor Infiltrating Lymphocytes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-01.

Spatiotemporal modulation of immune microenvironment via composite hydrogel brakes for diabetic wound healing

Uncontrolled programmed polarization of macrophages plays an important role in chronic diabetic wound healing. Therefore, correcting programmed macrophage polarization while inducing new tissue remodelling through materials and preventing scar formation is desirable. Herein, a composite hydrogel brake that enables spatiotemporal regulation of the immune microenvironment was constructed to promote skin tissue regeneration. The system was based on thiolated hyaluronic acid to reshape the programmed polarization of macrophages, methacrylate gelatin as a mechanical support, and poly (L-lactic acid) nanoparticles loaded with TGF-β receptor antagonists to inhibit scar formation. Notably, the composite hydrogel acts as a double brake: in the early stage, self-induced M2-type polarization is achieved with the help of thiols; the TNF and NLRP signalling pathways are downregulated; and the immune microenvironment is regulated. During tissue remodeling, the long-term biological effect of TGF-β secretion by M2-type macrophages is interrupted by the slow release of antagonists, which inhibits excessive collagen deposition and prevents scar formation. The dual effect of restraint on reprogramming macrophage polarization and inhibiting scar formation was further confirmed in a diabetic rat skin defect model. Therefore, based on the immunological mechanism, a composite hydrogel brake was specifically designed to regulate the immune microenvironment, induce new tissue remodelling, and provide a promising clinical strategy for treating chronic diabetic wounds.

Berberine alleviates diabetic retinopathy by regulating the Th17/Treg ratio

BackgroundDiabetic retinopathy (DR) stands as a prominent complication of diabetes. Berberine (BBR) has reported to be effective to ameliorate the retinal damage of DR. Studying the potential immunological mechanisms of BBR on the streptozotocin (STZ) induced DR mouse model will explain the therapeutic mechanisms of BBR and provide theoretical basis for the clinical application of this drug. MethodsC57BL/6J mice were induced into a diabetic state using a 50 mg/(kg·d) dose of STZ over a 5-day period. Subsequently, they were subjected to a high-fat diet (HFD) for one month. Following a 5-week treatment with 100 mg/(kg·d) BBR, the concentrations of inflammatory factors in the mice's peripheral blood were determined using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin staining was employed to scrutinize pathological changes in the mice's retinas, while flow cytometry assessed the proportions of T-lymphocyte subsets and the activation status of dendritic cells (DCs) in the spleen and lymph nodes. CD4+T cells and DC2.4 cell lines were utilized to investigate the direct and indirect effects of BBR on T cells under high glucose conditions in vitro. ResultsFollowing 5 weeks of BBR treatment in the streptozotocin (STZ) mouse model of DR, we observed alleviation of retinal lesions and a down-regulation in the secretion of inflammatory cytokines, namely TNF-α, IL-1β, and IL-6, in the serum of these mice. And in the spleen and lymph nodes of these mice, BBR inhibited the proportion of Th17 cells and promoted the proportion of Treg cells, thereby down-regulating the Th17/Treg ratio. Additionally, in vitro experiments, BBR directly inhibited the expression of the transcription factor RORγt and promoted the expression of the transcription factor Foxp3 in T cells, resulting in a down-regulation of the Th17/Treg ratio. Furthermore, BBR indirectly modulated the Th17/Treg ratio by suppressing the secretion of TNF-α, IL-1β, and IL-6 by DCs and enhancing the secretion of indoleamine 2,3-dioxygenase (IDO) and transforming growth factor-beta (TGF-β) by DCs. This dual action inhibited Th17 cell differentiation while promoting Treg cells. ConclusionOur findings indicate that BBR regulate T cell subpopulation differentiation, reducing the Th17/Treg ratio by directly or indirectly pathway. This represents a potential therapeutic avenue of BBR for improving diabetic retinopathy.

Maternal-fetal immunity and recurrent spontaneous abortion.

Recurrent Spontaneous Abortion (RSA) is a common pregnancy complication, that has multifactorial causes, and currently, 40%-50% of cases remain unexplained, referred to as Unexplained RSA (URSA). Due to the elusive etiology and mechanisms, clinical management is exceedingly challenging. In recent years, with the progress in reproductive immunology, a growing body of evidence suggests a relationship between URSA and maternal-fetal immunology, offering hope for the development of tailored treatment strategies. This article provides an immunological perspective on the pathogenesis, diagnosis, and treatment of RSA. On one hand, it comprehensively reviews the immunological mechanisms underlying RSA, including abnormalities in maternal-fetal interface immune tolerance, maternal-fetal interface immune cell function, gut microbiota-mediated immune dysregulation, and vaginal microbiota-mediated immune anomalies. On the other hand, it presents the diagnosis and existing treatment modalities for RSA. This article offers a clear knowledge framework for understanding RSA from an immunological standpoint. In conclusion, while the "layers of the veil" regarding immunological factors in RSA are gradually being unveiled, our current research may only scratch the surface. In terms of immunological etiology, effective diagnostic tools for RSA are currently lacking, and the efficacy and safety of immunotherapies, primarily based on lymphocyte immunotherapy and intravenous immunoglobulin, remain contentious.

Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.

While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied. Patients with GABABR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples. A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (p = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up (p = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs. Nonparaneoplastic GABABR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABABR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.

Immune response of BALB/c mice infected with two strains of Corynebacterium pseudotuberculosis

This work evaluated aspects of the immune response of BALB/c mice infected with Corynebacterium pseudotuberculosis (T1 and C57). The fifteen BALB/c mice were euthanized after 70 days of infection and morphologically evaluated, also analyzing the innate and adaptive immune responses. The C57 strain induced more pronounced morphological changes than the T1 strain. There was an increase in CD4+ and CD8+ T cells identified during infection with the C57 strain. Cytokines of the inflammatory profile IL-1α and IL-6 and regulatory IL-13 and IL-10 presented significant differences. Cytokines IL-2, IL-4, INF-γ, IL-22, IL-21, and IL-27 did not differ significantly between groups. The obtained results contribute to a better understanding of the type of response and the immunological mechanisms involved during infection with different strains of C. pseudotuberculosis.

The immunopathogenesis of sarcoidosis

Sarcoidosis is a granulomatous multiorgan disease, thought to result from exposure to yet unidentified antigens in genetically susceptible individuals. The exaggerated inflammatory response that leads to granuloma formation is highly complex and involves the innate and adaptive immune system. Consecutive immunological studies using advanced technology have increased our understanding of aberrantly activated immune cells, mediators and pathways that influence the formation, maintenance and resolution of granulomas. Over the years, it has become increasingly clear that disease immunopathogenesis can only be understood if the clinical heterogeneity of sarcoidosis is taken into consideration, along with the distribution of immune cells in peripheral blood and involved organs. Most studies offer an immunological snapshot during disease course, while the cellular composition of both the circulation and tissue microenvironment may change over time. Despite these challenges, novel insights on the role of the immune system are continuously published, thus bringing the field forward.This review highlights current knowledge on the innate and adaptive immune responses involved in sarcoidosis pathogenesis, as well as the pathways involved in non-resolving disease and fibrosis development. Additionally, we describe proposed immunological mechanisms responsible for drug-induced sarcoid like reactions. Although many aspects of disease immunopathogenesis remain to be unraveled, the identification of crucial immune reactions in sarcoidosis may help identify new treatment targets. We therefore also discuss potential therapies and future strategies based on the latest immunological findings.

Peripheral Neuropathy and Muscle Disorders as Immune-Related Adverse Events

Neurological immune-related adverse events (irAEs) associated with cancer treatment with immune checkpoint inhibitors (ICI) present diverse clinical characteristics. Neurological irAEs affect the peripheral nervous system and muscles more than they affect the central nervous system. Among the various subsets of peripheral neuropathies, polyradiculoneuropathy, which includes Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy, stands out as the most severe form, leading to significant muscle weakness. ICIs can induce dysautonomia, including autoimmune autonomic ganglionopathy. Autonomic neuropathy represents a neurological irAE. Neurological irAEs of neuromuscular junctions include myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS). Diagnosing MG or myositis independently can be challenging when they occur as irAEs. Myocarditis is sometimes observed as an irAE in patients with MG and can cause both severe heart failure and lethal arrhythmias, resulting in fatal outcomes. Anti-Kv1.4 antibodies are biomarkers of the severe form of MG and myocarditis. The administration of ICI in patients with small cell lung cancer increases the risk of LEMS. The distinction between LEMS is an irAE or a manifestation of paraneoplastic neurological syndrome is unclear as both conditions share common immunological mechanisms.

Blood Group Variations in COVID-19 Convalescent Plasma and Regular Blood Donors: A Comparative Analysis in the Serbian Population

This research explores the association between ABO blood groups and susceptibility to SARS-CoV-2 infection, analyzing Convalescent COVID-19 plasma (CCP) donors (n = 500) and healthy whole blood donors (BDs) (n = 9678) during the pandemic (1 May 2020 to 30 April 2021). A comparison is made with pre-pandemic BDs (n = 11,892) from 1 May 2018 to 30 April 2019. Significant differences in blood group distribution are observed, with blood group A individuals being three times more likely to be CCP donors. Conversely, blood groups B, O, and AB are less associated with CCP donation. Notably, blood group O is more prevalent among regular BDs, suggesting potential resistance to SARS-CoV-2 infection. This study underscores variations in blood group distribution during the pandemic compared to pre-pandemic periods. The findings support previous research indicating a link between blood group antigens and viral susceptibility, including SARS-CoV-2. Understanding these associations has implications for public health strategies, with potential for predicting COVID-19 outcomes and transmission patterns. Further research is crucial to explore molecular and immunological mechanisms, providing valuable insights for targeted preventive strategies and personalized healthcare in managing the impact of COVID-19.

Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies. In this narrative review, we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease, immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following. We focused on the anti-gliadin antibodies, antibodies to different isoforms of tissue transglutaminase (TG) (anti-TG2, 3, and 6 antibodies), anti-glycine receptor antibodies, anti-glutamine acid decarboxylase antibodies, anti-deamidated gliadin peptides antibodies, etc. Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction, presented as different neurological disorders. We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

A Bibliometric Analysis of Literature on the Impact of Rheumatoid Arthritis on Oral Health (1987-2024).

This bibliometric analysis investigates the research landscape concerning the impact of rheumatoid arthritis (RA) on oral health through a comprehensive literature review. The study includes all English-language articles retrieved from the PubMed database, focusing on the relationship between RA and various aspects of oral health without any filter. The analysis of 261 publications revealed fluctuations in publication patterns from 1987 to 2024, with notable surges and declines in research activity. Collaborative networks among authors and institutions were identified, highlighting key contributors and prolific institutions such as Karolinska Institutet. The themes prevalent in the research included demographics, oral microbiota, biomarkers, treatment outcomes, and molecular mechanisms. Trend topic and thematic evolution analyses elucidated shifts in research focus from traditional concerns to emerging areas such as oral microbiology and immunological mechanisms. Key findings underscored the need for more clinical trials to comprehend the impact of RA on oral health, enhanced interdisciplinary collaboration, exploration of emerging areas, and longitudinal studies. This analysis provides valuable insights into the evolving research landscape, informing future investigations and interventions to improve oral health outcomes in individuals with RA.

Gut bacterium Burkholderia cepacia (BsNLG8) and immune gene Defensin A contribute to the resistance against Nicotine-induced stress in Nilaparvata lugens (Stål)

Nicotine, a naturally occurring alkaloid found in tobacco, is a potent neurotoxin extensively used to control Nilaparvata lugens (Stål), a destructive insect pest of rice crops. The insect gut harbors a wide array of resident microorganisms that profoundly influence several biological processes, including host immunity. Maintaining an optimal gut microbiota and immune homeostasis requires a complex network of reciprocal regulatory interactions. However, the underlying molecular mechanisms driving these symbiotic exchanges, particularly between specific gut microbe and immunity, remain largely unknown in insects. Our previous investigations identified and isolated a nicotine-degrading Burkholderia cepacia strain (BsNLG8) with antifungal properties. Building on those findings, we found that nicotine intake significantly increased the abundance of a symbiotic bacteria BsNLG8, induced a stronger bacteriostatic effect in hemolymph, and enhanced the nicotine tolerance of N. lugens. Additionally, nicotine-induced antimicrobial peptides (AMPs) exhibited significant antibacterial effects against Staphylococcus aureus. We adopted RNA-seq to explore the underlying immunological mechanisms in nicotine-stressed N. lugens. Bioinformatic analyses identified numerous differentially expressed immune genes, including recognition/immune activation (GRPs and Toll) and AMPs (i.e., Defensin, Lugensin, lysozyme). Temporal expression profiling (12, 24, and 48 hours) of immune genes revealed pattern recognition proteins and immune effectors as primary responders to nicotine-induced stress. Defensin A, a broad-spectrum immunomodulatory cationic peptide, exhibited significantly high expression. RNA interference-mediated silencing of Defensin A reduced the survival, enhanced nicotine sensitivity of N. lugens to nicotine, and decreased the abundance of BsNLG8. The reintroduction of BsNLG8 improved the expression of immune genes, aiding nicotine resistance of N. lugens. Our findings indicate a potential reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine stress. Moreover, this study offers novel and valuable insights for future research into enhancing nicotine-based pest management programs and developing alternative biocontrol methods involving the implication of insect symbionts.

Targeted treatments for immune dysregulation in inborn errors of immunity

Primary immune regulatory disorders (PIRDs) constitute a subset of inborn errors of immunity and are characterized by lymphoproliferation, autoimmunity, malignancy, and infection. Unlike classical primary immune deficiencies, initial symptoms of PIRDs can manifest as autoimmunity such as cytopenias or enteropathy, which can often prove resistant to conventional treatments and occur years prior to the onset of infectious complications. Raising awareness about PIRDs among specialists and adopting a multidisciplinary approach is crucial for early diagnosis, intervention, and potential prevention of severe organ damage. Significant progress has been made in identifying several PIRDs, which has contributed to a more comprehensive comprehension of their underlying immunological mechanisms. This knowledge has paved the way for targeted therapies focusing on specific molecules, which tend to offer superior disease control compared to traditional immunosuppressants. This review, informed by the latest literature, explores prevalent PIRDs, detailing their clinical manifestations and recent advancements in treatment modalities.

Decreased exercise-induced natural killer cell redistribution in multiple sclerosis

BackgroundExercise may have beneficial effects in MS, remaining controversial its possible disease-modifying effects and which mechanisms might be involved. We evaluated whether exercise-induced lymphocyte redistribution differ in MS patients as compared to controls. MethodsExercise was assessed in 12 relapsing-remitting MS patients and 11 controls in a cycle ergometer, obtaining blood samples before exercise, at maximal exercise capacity (T1), and after resting (T2). Peripheral lymphocytes were evaluated by flow cytometry, assessing chemokine receptor expression to study cell trafficking properties. ResultsLymphocyte subsets in all cases increased after exercise and decreased at resting. However, total natural killer (NK) cells in patients as compared to controls had a lower exercise-induced redeployment at T1 (696 ± 581 cells/µL vs.1502 ± 641 cells/µL, p < 0.01). Evaluating NK cell subsets, CD56bright NK cells numbers decreased in peripheral blood in MS patients after resting (T2), contrasting with values remaining above baseline in healthy controls. NK cells mobilized after exercise at T1 in controls, as compared to patients, had a higher CX3CR1 expression (1402 ± 564/µL vs. 615 ± 548 cell//µL, p < 0.01). ConclusionExercise-induced redeployment of NK cells may be reduced in MS patients, as well as their migration capabilities, pointing to potential immunological mechanisms to be enhanced by exercise training programs.

Allergic Contact Dermatitis: Causes, Symptoms, and Specific Therapies

Objective: The present study aims to deepen understanding of Allergic Contact Dermatitis (ACD), exploring its etiology, immunological mechanisms, diagnostic methods, and updated therapeutic strategies to improve treatment and quality of life for patients.   Theoretical Framework: The research is grounded in studies of the immunological processes involved in ACD, with an emphasis on the sensitization of memory T lymphocytes, and the diversity of causative agents, ranging from chemicals to natural substances.   Method: A methodological approach that includes a systematic literature review and analysis of relevant case studies was adopted, with special attention to the use of the patch test as a diagnostic tool for identifying specific allergens.   Results and Discussion: The findings highlight the importance of accurate diagnosis and correct identification of allergens via patch test, which are essential for effective disease management. Therapeutic options discussed range from topical corticosteroids to antihistamines, adjusted according to the severity of clinical manifestations.   Research Implications: This study underscores the importance of a multidisciplinary and evidence-based management approach in addressing ACD, integrating the latest scientific advances into daily clinical practices.   Originality/Value: The original contribution of this article lies in the integrative analysis and detailed practical recommendations for the treatment of ACD, providing new perspectives for the medical literature and clinical treatment of this complex condition.

Discovery and validation of molecular patterns and immune characteristics in the peripheral blood of ischemic stroke patients.

Stroke is a disease with high morbidity, disability, and mortality. Immune factors play a crucial role in the occurrence of ischemic stroke (IS), but their exact mechanism is not clear. This study aims to identify possible immunological mechanisms by recognizing immune-related biomarkers and evaluating the infiltration pattern of immune cells. We downloaded datasets of IS patients from GEO, applied R language to discover differentially expressed genes, and elucidated their biological functions using GO, KEGG analysis, and GSEA analysis. The hub genes were then obtained using two machine learning algorithms (least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE)) and the immune cell infiltration pattern was revealed by CIBERSORT. Gene-drug target networks and mRNA-miRNA-lncRNA regulatory networks were constructed using Cytoscape. Finally, we used RT-qPCR to validate the hub genes and applied logistic regression methods to build diagnostic models validated with ROC curves. We screened 188 differentially expressed genes whose functional analysis was enriched to multiple immune-related pathways. Six hub genes (ANTXR2, BAZ2B, C5AR1, PDK4, PPIH, and STK3) were identified using LASSO and SVM-RFE. ANTXR2, BAZ2B, C5AR1, PDK4, and STK3 were positively correlated with neutrophils and gamma delta T cells, and negatively correlated with T follicular helper cells and CD8, while PPIH showed the exact opposite trend. Immune infiltration indicated increased activity of monocytes, macrophages M0, neutrophils, and mast cells, and decreased infiltration of T follicular helper cells and CD8 in the IS group. The ceRNA network consisted of 306 miRNA-mRNA interacting pairs and 285 miRNA-lncRNA interacting pairs. RT-qPCR results indicated that the expression levels of BAZ2B, C5AR1, PDK4, and STK3 were significantly increased in patients with IS. Finally, we developed a diagnostic model based on these four genes. The AUC value of the model was verified to be 0.999 in the training set and 0.940 in the validation set. Our research explored the immune-related gene expression modules and provided a specific basis for further study of immunomodulatory therapy of IS.