Immunological Factors Research Articles

Histologic and immunologic factors associated with response to immune checkpoint inhibitors in advanced sarcoma.

To characterize factors associated with response to immune checkpoint inhibitors (ICIs) in advanced sarcoma. This is a retrospective study with a cohort of 216 patients with advanced sarcoma treated with ICIs between 2016-2023 at Stanford Health Care. Overall survival (OS), progression free survival (PFS), objective response rates per RECIST criteria (ORR), and reason for ICI discontinuation were analyzed across histologic subtypes, ICI regimens, tumor mutational burden (TMB), and PD-L1 expression. The overall ORR in the cohort was 16.7%. The histologic subtypes with the highest ORR were Kaposi sarcoma (KS, 66.7%), alveolar soft part sarcoma (ASPS, 50%), angiosarcoma (AS, 33.3%), myxofibrosarcoma (MFS, 28.6%), and undifferentiated pleomorphic sarcoma (UPS, 27.8%). The subtypes with the lowest ORR were osteosarcoma (0%), synovial sarcoma (SS, 0%), and liposarcoma (LPS, 3.7%). The subtypes with the highest median PFS were KS (median not reached, NR), ASPS (NR), MFS (27.4 months), and UPS (11.3 months). The ORR for sarcomas with PD-L1 ≥ 1% was 27.8% (p=0.02), while the ORR for sarcomas with TMB ≥ 10 mutations per megabase of DNA (mut/MB) was 28.6% (p=0.20). ORR and PFS were highly variable across sarcoma histologic subtype. In this large analysis, KS, ASPS, AS, MFS, and UPS demonstrated the highest ORR and longest PFS while osteosarcoma, SS, and LPS had the lowest ORR and shortest PFS. PD-L1 expression was also associated with increased ORR. Our findings provide further insight into understanding the sarcoma histologic and immunologic factors that correspond with response to ICIs.

Maximal mouth opening is a simple method to evaluate the treatment outcome of temporomandibular joint arthritis in patients with juvenile idiopathic arthritis.

Temporomandibular joint (TMJ) arthritis is a common finding in juvenile idiopathic arthritis (JIA) patients. TMJ arthritis can cause significant disturbances in TMJ function and growth without treatment. Our aim was to evaluate the effectiveness of medical treatments used to manage TMJ arthritis and how to evaluate the outcome of the treatment. Furthermore, this study aimed to ascertain the prevalence of TMJ arthritis in JIA patients and investigate the potential impact of specific factors. Between 2015 and 2019, a total of 194 JIA patients who received treatment at the Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Finland were included in the study. We retrospectively screened the patient records and imaging studies to find out how many patients had TMJ arthritis and what medication was used to treat it. Maximal incisal mouth opening (MIO) increased significantly with patients whose TMJ arthritis was successfully treated with intra-articular corticosteroid injection (IACI). Almost all patients with TMJ arthritis were treated with an IACI at some point during their treatment. Overall, 99 patients (51%) had been diagnosed with TMJ arthritis. No statistical difference was found between the prevalence of TMJ arthritis and different JIA subtypes, JIA onset time, gender, or immunological factors. MIO is an easy way to evaluate the treatment outcome and possible disease activation of TMJ arthritis. The prevalence of TMJ arthritis is high among JIA patients. In our study, we could not find any parameters that predict TMJ arthritis, and despite systemic medication, TMJ arthritis might occur.

Clinical progress in the development of CAR T cells to treat malignant glioma.

Chimeric antigen receptor (CAR) T cell therapy is an exciting modality of immunotherapy that has revolutionized the treatment of hematologic malignancies. However, translating this success to malignant gliomas such as glioblastoma (GBM) and diffuse midline glioma (DMG) remains a formidable challenge due to multiple biologic, anatomic, and immunologic factors. Despite these hurdles, a number of clinical trials deployed over the last decade have increased optimism for the potential of CAR T cell therapy in glioma treatment. We highlight historical and ongoing clinical trials of CAR T cell therapy in glioma, with a focus on key tumor-associated antigens such as IL-13Rα2, HER2, EGFR, EGFRvIII, EphA2, GD2, and B7-H3. Early studies established proof-of-concept for antigen-specific CAR T cell targeting, yet immune evasion mechanisms such as antigen downregulation and limited CAR T cell persistence remain significant obstacles. Recent approaches, including multiantigen targeting, alternative cell sources, and innovations in delivery routes offer promising strategies to overcome these challenges. The rapid evolution of investigational CAR T cell therapies portends great potential for the future of glioma treatment. Future studies will need to refine antigen targeting strategies, optimize CAR T cell persistence, and integrate combinatorial approaches to fully harness the therapeutic potential of this modality and improve the therapeutic window against brain tumors.

The N6-methyladenosine RNA epigenetic modification modulates the amplification of coxsackievirus B1 in human pancreatic beta cells

Type 1 diabetes (T1D) is characterized by a prolonged autoimmune attack resulting in the massive loss of insulin-producing beta cells. The initiation and progression of T1D depends on a complex interaction between genetic, immunological and environmental factors. Epidemiological, experimental and clinical evidence suggest a link between viral infections, particularly Coxsackievirus type B (CVB), and T1D development. Specifically, infections by the CVB serotype 1 (CVB1) contribute to the triggering of autoimmunity against beta cells in genetically predisposed individuals, and prolonged and probably non-lytic infections by CVB are associated with the development of T1D. However, the molecular mechanisms underlying CVB1 replication and establishing persistent infections in human pancreatic beta cells remain poorly understood. Here we show that the N6-methyladenosine (m6A) RNA epigenetic modification machinery regulates CVB1 amplification in the human beta cells. Using small interfering RNA (siRNA) targeting m6A writers and erasers, we observed that downregulation of m6A writers increases CVB1 amplification, while the downregulation of m6A erasers decreases it. Notably, the inhibition of Fat Mass and Obesity-associated protein (FTO), a key m6A eraser, reduced by 95% the production of infectious CVB1 in both human insulin-producing EndoC-βH1 cells and in induced pluripotent stem cell (iPSC)-derived islets. The FTO inhibitor reduced CVB1 expression within 6 h post-infection, suggesting a direct regulation of the CVB1 genome by m6A modification. Furthermore, in the absence of viral replication, FTO inhibition also decreased the translation of the incoming CVB1 genome, indicating that m6A plays a critical role in the initial stages of viral RNA translation. In addition, modulation of the m6A machinery affected the type I interferon response after poly-IC transfection, a mimic of RNA virus replication, but did not affect the cellular antiviral response in CVB1-infected cells. Altogether, these observations suggest that m6A directly affects CVB1 production. Our study provides the first evidence that the m6A epigenetic modification machinery controls CVB amplification in human pancreatic beta cells. This suggests that the m6A machinery is a potential target to control CVB infection in T1D and raises the possibility of an epigenetic control in the establishment of persistent CVB infections observed in the pancreas in individuals with type 1 diabetes.

Impact of Low-Dose Prednisolone on Pregnancy Viability in Women with Recurrent Pregnancy Loss of Unexplained Etiology

Recurrent pregnancy loss (RPL) of unexplained etiology presents a significant challenge in reproductive medicine, often leaving affected women with limited treatment options. Emerging evidence suggests that immunological factors may play a role in unexplained RPL, and corticosteroids like low-dose prednisolone could improve pregnancy outcomes by modulating immune responses. This retrospective cohort study examined the impact of low-dose prednisolone on pregnancy viability in women with a history of unexplained RPL. Medical records from reproductive health clinics were analyzed to compare outcomes between women receiving low-dose prednisolone (≤10 mg daily) and those not receiving any immunosuppressive treatment. Results demonstrated a statistically significant increase in pregnancy viability rates (68% in the prednisolone group vs. 45% in the non-treatment group, p < 0.05) and a decrease in miscarriage rates (30% vs. 55%, p < 0.01) among women using prednisolone. Furthermore, no significant differences in adverse maternal or fetal outcomes were observed, supporting the safety profile of low-dose prednisolone. The findings suggest that low-dose prednisolone may effectively improve pregnancy viability by modulating immune activity without substantial risks. However, further randomized controlled trials are needed to confirm these results and explore specific immunological pathways. This study underscores the potential of low-dose prednisolone as a promising treatment for unexplained RPL, offering new hope for affected women and paving the way for more targeted therapies in reproductive medicine. Keywords: Recurrent Pregnancy Loss, Low-Dose Prednisolone, Unexplained Pregnancy Loss, Immunomodulation, Pregnancy Viability, Miscarriage Reduction, Reproductive Immunology

Holstein × Montbéliarde-sired F1 generation crossbred female calves have an increased cellular immune response potential compared with purebred Holsteins

It is well known that crossbreds show many advantages over purebreds in improving calf health traits, but the immunological factors responsible for this heterosis remain largely unclear. The objective of this study was to compare the cellular immune responses and antibodies of Holstein (HO) and Montbéliarde-sired × Holstein (MH) F1 generation female calves, and investigate the effects of crossbreeding on the immunity. Fifty three-month-old healthy female calves (25 HO, 25 MH) were selected meticulously in a farm with the same criteria. Subsequently, complete blood count, flow cytometric analysis of T cell subsets and intracellular IFN-γ production, as well as indirect ELISA analysis of antibodies were performed in order to determine the immune profiles of the two groups of calves. We found that MH calves had higher percentage and number of CD4+ and CD8+ T cells than HO calves in the peripheral blood (p < 0.05), with higher MFI of CD44 on CD4+ and CD8+ T cells (p < 0.05). When stimulated by PMA and Ionomycin, the CD4+ and CD8+ T cells from MH calves secreted more IFN-γ than that of HO calves (p < 0.01). These results suggested that some immunological traits have been improved in MH calves, which may be an important cause of heterosis in crossbred animals.

Atopic Dermatitis: A Review of Diagnosis and Treatment

Atopic dermatitis, more commonly known as atopic eczema, is a chronic, relapsing inflammatory skin disorder characterized by dry skin, localized erythematous rash, and intense pruritus. The clinical manifestations are variable and age dependent. As one of the most common skin disorders globally, atopic dermatitis poses a significant clinical and economic burden on affected patients. Individual treatment strategies are imperative in improving patient outcomes and reducing these burdens. Recent advances in understanding the genetic, immunologic, and environmental factors influencing atopic dermatitis have opened avenues for novel treatment modalities. This article highlights the clinical presentation, pathophysiology, diagnosis criteria, as well as current recommendations on treatment of atopic dermatitis.

Prognostic Immunological Factors of Lymphogenic Metastasis in Colon Cancer

Введение. Корректная оценка стадии и прогноза является основой успешного лечения любой опухоли. Цель — оценить роль ряда иммунологических параметров локального иммунитета при раке ободочной кишки (РОК) в зависимости от распространенности процесса и на основании полученных данных разработать комплексную модель для определения вероятности лимфогенного метастазирования опухоли. Материалы и методы. В работу включено 50 пациентов РОК: c поражением лимфатических узлов (N+) — 27 пациентов (54 %), без поражения (N0) — 23 пациента (46 %). Из ткани опухоли, перитуморальной зоны (1–3 см от опухоли), линии резекции (~10 см от опухоли) была получена клеточная суспензия для выявления основных субпопуляций лимфоцитов, а также определения экспрессии TLRs (2, 3, 4) на CD45+(лимфоцитах), CD45-EpCAM+ (эпителиальные клетки). Статистический анализ результатов исследования проводился с помощью программы STATISTICA 13.3. Результаты. В тканях опухоли у пациентов с N0 увеличено количество T-лимфоцитов, натуральных киллеров (NK). В перитуморальной зоне при N0 отмечено более низкое содержание CD19+, а при N+ — двойных позитивных лимфоцитов (ДП), NK (p &lt; 0,05). Для тканей опухолей группы N0, в отличие от N+, характерно уменьшение количества опухолевых клеток, экспрессирующих TLR3. В перитуморальной зоне обеих групп отмечено разнонаправленное изменение количества клеток, которые экспрессируют TLR2: уменьшение — при N0, увеличение — при N+(p &lt; 0,05). При анализе относительного количества лимфоцитов во фрагментах тканей первичных опухолей пациентов с N0 отмечено уменьшение относительного количества клеток, экспрессирующих TLR2, и увеличение экспрессирующих TLR3,4, а для пациентов N+ отмечено увеличение количества клеток, которые экспрессируют TLR4 в 2,5 раз (p &lt; 0,05). С помощью метода логистической регрессии была разработана комплексная модель для определения вероятности лимфогенного метастазирования РОК. Индивидуальные значения пациентов подставляются в математическую модель и рассчитывается вероятность N+ (диагностическая чувствительность — 89,1 %, специфичность — 88,2 %). Выводы. Предложенная модель позволит прогнозировать распространенность процесса на предоперационном этапе у больных РОК, а также может стать одним из методов уточняющей диагностики в стадировании процесса.

Biodevelopmental Correlates of Sexual Orientation in Men: Evidence from a Polish Sample.

Biological mechanisms proposed to play a role in the development of sexual orientation in men include hormonal, genetic, and immunological factors. The posited roles of these factors are not mutually exclusive; instead, they may be at play to different degrees in different individuals. Direct measurement of these influences is challenging; thus, researchers rely on putative markers. We collected data on five well-established markers in a sample of gay and heterosexual men. We then (1) compared the levels of those markers in gay and straight men, (2) identified latent profiles based on those markers, and (3) compared the proportions of gay and straight men within the profiles. Gay men reported less gender conformity in childhood, a higher proportion of older brothers, were more right-handed, had more non-heterosexual relatives, and had more feminized digit ratios. Of the six identified profiles, the most numerous, containing a significantly higher proportion of straight men, had masculine digit ratios, masculine behavior in childhood, and was the most right-handed. Proportions of gay and straight men did not differ in the profile with the most feminine digit ratio, the profile associated with the highest proportion of older brothers, and the profile associated with left-handedness. Two remaining profiles, associated with familiality, and the most feminine childhood gender behaviors, consisted predominantly of gay men. The study suggests that further investigations of differences within sexual orientation categories are warranted.

Comprehensive treatment efficacy assessment of chronic recurrent aphthous stomatitis in patients with urogenital infections

Background: Infectious-allergic, neurogenic, occupational, immunological, and crossover factors play a significant role in the etiopathogenesis of chronic recurrent aphthous stomatitis (CRAS). Moreover, CRAS is associated with chronic kidney disease (CKD) and viral infections of the oral cavity secondary to urogenital pathologies. Aim: To assess the efficacy of comprehensive diagnosis and treatment of CRAS in patients with urogenital infections. Materials and methods: The study included 120 patients with CRAS aged 18–70 years. Of these, 80 had CRAS secondary to CKD with infectious complications: treatment group 1 (TG1, n=40) and reference group (RG, n=40). Forty patients with CRAS had no urogenital infections: treatment group 2 (TG2). The treatment protocol in the study groups included antihistamines, sedatives, immunomodulators, and multivitamins. Topical treatment included Eludril solution (irrigation, mouth wash, etc.), as well as ginger and myrrh extracts. The conditional control group (CCG) included 20 apparently healthy subjects. Results: The study found that regional lymphadenitis, Mikulicz’s aphthae, swollen oral mucosa, severe dental caries, and a high periodontal disease index were more common in patients with CRAS secondary to CKD; patients with more prolonged and severe CRAS had the worst results. Immunodeficiency and abnormal blood chemistry findings associated with CKD were identified as the primary pathogenetic factors for recurrent infection in CRAS. Conclusion: Patients with CRAS secondary to CKD may develop chronic inflammation caused by opportunistic pathogens in the oral cavity, resulting in local immunodeficiency, which is largely determined by the site and severity of inflammation.

Attitudes and Perception of Nursing Mothers towards Exclusive Breastfeeding in the Federal Capital Territory (FCT)

Breastfeeding is one of the oldest practices known to mankind because the breastmilk contains the essential fats, proteins, carbohydrates, and immunological factors needed for infants to thrive. This study assessed the attitude and perception of nursing mothers towards exclusive breastfeeding. An evaluation was conducted to assess the attitude and perception using a qualitative research method which involved 401 nursing mothers in the Federal Capital Territory (FCT) who were selected randomly to answer questionnaires regarding their knowledge and practice of exclusive breastfeeding. The data was analysed using the chi-square test. The result was presented using frequency tables and charts, the chi-square was used to test for hypotheses between variables. 344 of 401 respondents (85.7%) have a good understanding of exclusive breastfeeding. 280 of 401 respondents (69.8%) practice exclusive breastfeeding, 167 of 401 respondents (41.64%) were informed about exclusive breastfeeding from healthcare practitioners and 121 of 401 respondents (30.17%) heard about it from family members. From this study, we derived that the level of education, marital status, income level and religious beliefs have no significant effect on exclusive breastfeeding. This study highlighted that majority of the respondents have knowledge of exclusive breastfeeding and practice it. It is necessary to provide lactation services especially to new mothers during the antenatal and postnatal care, fathers should be made aware of the benefits of exclusive breastfeeding and the importance of supporting the nursing mothers by feeding them healthy meals which would help nourish both the mother and infant. Exclusive breastfeeding is recommended for the first six months of a child’s life.

Temporal genomic analysis of homogeneous tumor models reveals key regulators of immune evasion in melanoma

Abstract Low intra-tumor heterogeneity (ITH) correlates with increased patient survival and immunotherapy response. However, even highly homogeneous tumors are variably aggressive, and the immunological factors impacting aggressiveness remain understudied. Here, we analyzed the mechanisms underlying immune escape in murine tumors with low ITH. We used immunophenotyping and single-cell RNA sequencing to compare the temporal growth of in-vivo transplanted, genetically similar rejected vs. non-rejected single-cell clones. Non-rejected clones showed high infiltration of tumor-associated macrophages (TAMs), lower T-cell infiltration, and increased T-cell exhaustion compared to rejected clones. Comparative analysis of rejection-associated gene expression programs, combined with in-vivo CRISPR knockout screens of candidate regulators, identified Mif (macrophage migration inhibitory factor) as a major contributor to immune rejection. Mif knockout resulted in smaller tumors and reduced TAM infiltration. These results were validated in melanoma patient data. Overall, our homogeneous tumor system can uncover factors regulating growth variability and identifies Mif as critical in aggressive melanoma.

From immune response to mental health: neutrophils in schizophrenia

Schizophrenia is a multifaceted psychiatric disorder with a complex etiology that includes genetic, environmental, and immunological factors. Emerging research has increasingly focused on the role of the immune system, particularly neutrophils, in the pathogenesis of schizophrenia. Neutrophils, the most abundant type of white blood cells, are crucial in the body’s defense mechanisms against infections and in the regulation of inflammation. This review explores the evolving evidence that implicates neutrophils in schizophrenia, highlighting their potential contribution to the disorder’s onset and progression through mechanisms such as neuroinflammation and oxidative stress. Recent studies have demonstrated elevated neutrophil counts and neutrophil-to-lymphocyte ratios (NLR) in individuals with schizophrenia, correlating with the severity of psychotic symptoms and cognitive impairments. Furthermore, genetic and molecular analyses have revealed abnormalities in neutrophil function and immune-related gene expression in schizophrenia patients. These findings suggest that neutrophil dysfunction and the resulting chronic inflammation could play a significant role in the disorder’s pathophysiology, affecting neuronal function and contributing to the clinical manifestations of schizophrenia. Neutrophil-related biomarkers, such as NLR, could aid in the diagnosis and monitoring of disease progression. Additionally, targeting neutrophil activity and associated inflammatory pathways presents a promising avenue for developing new therapeutic interventions. This review underscores the need for further research to elucidate the precise mechanisms by which neutrophils influence schizophrenia and to explore potential treatments that could improve outcomes for patients.

NCMP-22. CO-OCCURRENCE OF MULTIPLE SCLEROSIS AND HODGKIN LYMPHOMA. IS THERE A COMMON PATHOPHYSIOLOGY?

Abstract BACKGROUND Multiple sclerosis (MS) and Hodgkin lymphoma (HL) share common epidemiology, genetics and immunological factors. Both affect immune activation, cell proliferation and lymphocyte-mediated immunity. However, occurrence of these two distinct clinical conditions is rare. We present a case of a woman with transverse myelitis fulfilling criteria for MS with synchronous HL. CASE REPORT A 37-year-old woman presented to the emergency room with bilateral leg weakness, numbness and urinary retention. A contrasted MRI of the brain and thoracic spine showed non-specific, non-enhancing white-matter lesions in the brain, and patchy areas of peripheral contrast-enhancement with T2-hyperintensity in the thoracic cord. Treatment with steroid infusion resulted in mild improvements of leg weakness and numbness. Cerebrospinal fluid (CSF) demonstrated oligoclonal bands (OCB) and increased IgG index. Serum was positive for JCV antibody. Due to the atypical MRI findings, namely the peripheral nature of thoracic contrast-enhancement, we were concerned for other inflammatory or autoimmune etiologies. A computed tomography of the chest, abdomen and pelvis revealed a large mediastinal mass and enlarged lymph nodes. A biopsy revealed classic HL. Three-months later, a follow-up MRI brain showed worsening contrast-enhanced lesions. A repeat CSF study revealed normal OCBs and IgG index. CSF was negative for malignant cells and JC virus DNA. To rule out a rare possibility of central nervous system HL, a biopsy of an enhancing brain lesion was obtained, which showed focal gliosis and focal perivascular lymphocytic infiltrates. No malignant cells were observed. She was diagnosed with multiple sclerosis and started systemic chemotherapy (doxorubicin, bleomycin, dacarbazine and vinblastine) for HL. CONCLUSIONS We report a case of an atypical transverse myelitis with HL. Although familial genetic clustering has been described, other potential common risk-factors between MS and HL are Epstein-Barr Virus infection and immunologic overlap, particularly in the context of lymphocyte-mediated immunity.

Comprehensive Characterization of Anti-HLA and Non-HLA Antibodies in Patients on Kidney Transplant Waiting List and Evaluation of Their Impact on Alloimmunization Risk and Dialysis Treatment.

Alloimmunization remains a major obstacle to successful kidney transplantation, mainly due to the formation of anti-HLA antibodies. In recent years, non-HLA antibodies have emerged as additional immunologic factors that can potentially contribute to graft rejection. The aim of this study was to investigate the prevalence and specificity of both anti-HLA and non-HLA antibodies in patients with end-stage renal disease on a waiting list for kidney transplantation. Serum samples from 74 patients were analyzed using complement-dependent cytotoxicity and solid-phase assays. IgG anti-HLA antibodies were identified in 43.2% of participants, while IgG non-HLA antibodies were detected in 91.9%. The most frequent non-HLA antibodies included anti-ENO1 (28.4%), anti-FIBR1 (23.0%) and anti-PRKCZ (23.0%). A significant difference was found between the number of distinct IgG anti-HLA and IgG non-HLA antibody specificities. However, no significant correlation was found between the number of IgG non-HLA antibody specificities and previous alloimmunization events or dialysis treatments. These results suggest that non-HLA antibodies, although often overlooked, can sometimes play a critical role in transplant outcomes. Routine testing for non-HLA antibodies, in addition to mandatory anti-HLA antibody screening and identification, could improve immunologic risk assessment in transplant patients and post-transplant care.

In Silico Study Active Compounds of Jamu Against Pre-Eclampsia Through Anti-Vasoconstriction and Anti-Inflammation

Preeclampsia is one of serious pregnancy-related condition that marked by elevated blood pressure and proteinuria that typically emerges during the second trimester or above 20 week, this disease become the second common cause of maternal death globally per year. One factors that can initiate preeclampsia are immunologic factor. Preeclampsia is started with abnormal trophoblast development and poor or shallow placental blood vessel development. Several protein that are induce by pre eclampsia are ACE1 (as vasoconstrictor), p38α, and JNK (stress-related protein and induce inflammation). One of the natural medicine in Indonesia is a “Jamu” that refers to traditional herbal medicine derived from natural ingredients such as herbs, roots, and spices.. In this research we are trying to predict several compounds in early-month pregnant jamu to tackle activation of ACE1, JNK, and p38α. Firstly, all of jamu compound was screened using Lipinski and bioavaibility test. Then, all of the jamu compound that pass the test before will be docked with ACE1, JNK, and p38α using Vina wizard in PyRx. The highest affinity in docking result will be visualized using Biovia Discovery Studio 2019, and will advance to molecular dynamics simulation test to determine stability of the complex in cell environment. The result show that kaempferol can stabily bind to p38α protein, with only induce minimum fluctuation in all RMSD and RMSF result. Piperanine can stabily bind JNK protein with also minimum fluctuation in all RMSD and RMSF result. Both kaempferol and piperanine did’t violate any Lipinski rule and Bioavaibility test.

Transient biopsy-proven progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS) in an elderly woman without known immunodeficiency: a case report

BackgroundProgressive multifocal leukoencephalopathy (PML) is a severe opportunistic brain disease caused by lytic JC polyomavirus (JCPyV) replication in oligodendrocytes. Although JCPyV infection is common in the general population, PML almost exclusively occurs in patients immunocompromised due to untreated HIV/AIDS, haematological malignancies, primary immunodeficiencies, solid organ transplantation, or immunomodulatory treatment of autoimmune diseases. There is no effective antiviral treatment, and recovery depends on immune reconstitution. Paradoxically, initiation of antiretroviral therapy for HIV/AIDS or interruption of immunomodulating treatment can worsen the clinical manifestations due to immune reconstitution inflammatory syndrome (IRIS). Here, we report an unusual case of spontaneous IRIS in a 76-year-old immunocompetent woman, unmasking PML and leading to unexpected recovery.Case presentationThe patient was admitted to the hospital due to psychosis, speech impairment, and behavioral changes over the last three months. She had previously been healthy, except for a cerebellar stroke secondary to paroxysmal atrial fibrillation. Magnetic resonance imaging (MRI) revealed multiple contrast-enhancing white matter lesions suspicious of cancer metastases. Due to suspicion of edema, dexamethasone was administered, and the patient was released while waiting for a stereotactic brain biopsy. Eight days later, she suffered tonic seizures and was readmitted. Intravenous levetiracetam gave rapid effect, but the patient was paranoid and non-cooperative, and dexamethasone was unintentionally discontinued. Ten days later, the brain biopsy revealed demyelination, abundant perivascular T cells, macrophages, and scattered JCPyV-infected oligodendrocytes, rendering the diagnosis of PML-IRIS. The cerebrospinal fluid contained low amounts of JCPyV-DNA, and plasma contained high levels of anti-JCPyV immunoglobulin G. Despite extensive immunological testing, no evidence of immunodeficiency was found. The patient gradually recovered clinically and radiologically. More than 19 months after diagnosis, the patient has only a slight impairment in language and behavior.ConclusionsAn apparently immunocompetent elderly person developed clinically symptomatic PML, which spontaneously resolved with symptoms and signs of IRIS. The atypical MRI lesions with contrast enhancement and the lack of known immunological risk factors for PML delayed the diagnosis, eventually proved by biopsy. PML and PML-IRIS should be considered in the differential diagnosis of patients presenting CNS symptoms and focal lesions with contrast enhancement on MRI.

Viral and immune predictors of HIV posttreatment control.

This review focuses on the viral and immune factors influencing HIV posttreatment control (PTC), a rare condition where individuals maintain viral suppression after discontinuing antiretroviral therapy (ART). Studies demonstrate that early ART initiation leads to smaller HIV reservoirs and delayed viral rebound in PTCs. Virologically, PTCs harbor smaller HIV reservoirs and show lower levels of reservoir transcriptional activity compared with posttreatment noncontrollers. Immunologically, PTCs exhibit distinct T-cell dynamics, with reduced CD4+ and CD8+ T-cell activation and exhaustion, enhanced natural killer (NK) cell activity, and enhanced proliferative responses of HIV-specific CD8+ T cells post-ART interruption. Additionally, humoral immunity, particularly the development of autologous neutralizing antibodies (aNAbs), plays a role in viral control, though broadly neutralizing antibodies (bnAbs) are rare. The mechanisms behind posttreatment control are multifactorial, involving virological and immunological factors. Early ART initiation, a smaller and less transcriptionally active HIV reservoir, and immune responses including proliferative T-cell activity and NK cell function are key contributors to achieving ART-free HIV remission.

DUPILUMAB: A NEW ALLY FOR THE TREATMENT OF EOSINOPHILIC ESOPHAGITIS?

INTRODUCTION: Eosinophilic esophagitis is a chronic, immune-mediated disease of the gastrointestinal tract, resulting from the interaction between genetic, environmental and immunological factors of the affected patient. The clinical picture is characterized by esophageal dysfunction, which may present as dysphagia, precordial pain, upper abdominal pain or food impaction. Treatment aims to improve clinical symptoms and prevent disease progression and subsequent complications. In this context, immunobiologicals are emerging and promising therapies, with Dupilumab being the first specific treatment approved by the FDA. It is an IgG4 monoclonal antibody that targets IL-4R alpha and, from there, reduces protein transphorylation, transcription and the T helper 2-regulated response. The objective of this systematic review is to evaluate the efficacy of this drug in the treatment of eosinophilic esophagitis, in comparison with the options already available on the market. METHOD: PubMed searches were performed using the keywords “eosinophilic esophagitis dupilumab” and “dupilumab treatment esophagitis eosinophilic”. Initially, 60 results were obtained, but after exclusion by title, abstract and full text, 14 articles were included. RESULT: all articles analyzed demonstrated improvement in patients using Dupilumab, with 13 of them indicating a reduction in eosinophil counts, 8 showing clinical improvement in symptoms, 8 indicating histological improvement, 7 indicating improvement in the endoscopic pattern, according to the Endoscopic Reference for Eosinophilic Esophagitis, and 4 indicating a reduction in the Dysphagia Symptom Questionnaire (DQQ) score. DISCUSSION: eosinophilic esophagitis is a rare disease, but with potential for progression, negatively interfering with the patient's quality of life. Therefore, since current drug therapy is nonspecific, the use of Dupilumab presents itself as an innovative and optimistic solution for the future, because it changes the understanding of disease management, expands therapeutic options and improves prognosis. CONCLUSION: the use of Dupilumab in the treatment of eosinophilic esophagitis has proven to be effective. However, for the treatment to be well established with regard to the doses used, frequency of administration and longitudinal monitoring, further studies are still required.

Potential advantage of Therapeutic Plasma Exchange over Intravenous Immunoglobulin in children with axonal variant of Guillain-Barré syndrome: A report of six paediatric cases

Guillain-Barre syndrome (GBS) is a disease entity described in literature since 1859. It is associated with various etiological, clinical and immunological factors with prognostic predictive value. Both Intravenous immunoglobulin (IVIG) and Therapeutic Plasma Exchange (TPE) have been regarded as the first-line treatment for GBS. Certain diagnostic tools help us in early identification of GBS subtypes that may aid clinical management. Here, we have discussed six paediatric cases of GBS of Acute Motor Axonal Neuropathy (AMAN) subtype that were considered for TPE. 5 out of 6 patients were eventually weaned from mechanical ventilation and discharged from the hospital. This study emphasizes the role of TPE in management of severe IVIG refractory GBS with axonal involvement that can be beneficial to the patient. TPE may be considered early in GBS cases with axonal involvement.