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Immuno

Immuno is an international, peer-reviewed, open access journal on immunological research and clinical applications published quarterly online by MDPI.

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All Articles (273)

  • Review
  • Open Access

Dysregulation of the Bone Marrow Immune Microenvironment and Clinical Outcomes in Multiple Myeloma

  • Maria P. Ghirardi,
  • Patricia Brandalise and
  • Ademar D. Da Cunha Junior
  • + 9 authors

Multiple myeloma (MM) is characterized not only by malignant plasma cell proliferation but also by progressive dysregulation of the bone marrow immune microenvironment (BMIME). Increasing evidence suggests that disease progression, therapeutic resistance, and clinical outcomes are associated with dynamic interactions between tumor cells, immune populations, stromal elements, and inflammatory signaling pathways within the marrow niche. Although many of these observations derive from high-dimensional immune profiling, spatial transcriptomics, and single-cell transcriptomic studies, emerging mechanistic and functional evidence supports an important role for immune dysregulation in shaping disease evolution, immune escape, and therapeutic responsiveness. Recent advances in spatial profiling, immune phenotyping, and multi-omic approaches have revealed profound remodeling of the immune ecosystem across the evolution from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to symptomatic MM. This remodeling is characterized by progressive T-cell exhaustion, immunosenescence, dysfunction of natural killer (NK) cells, expansion of immunosuppressive myeloid populations, and altered cytokine and ligand–receptor signaling networks associated with adverse clinical outcomes. Importantly, emerging studies demonstrate that immune signatures derived from the BMIME may improve prognostic stratification beyond conventional tumor cytogenetics and staging systems. In this review, we discuss the mechanisms underlying immune dysregulation in MM, summarize recent discoveries regarding immune remodeling associated with clinical outcomes, and explore the translational implications of immune-based biomarkers and therapeutic strategies. Understanding the dynamic interplay between tumor genetics, immune-cell states, immunosenescence, and microenvironmental remodeling may facilitate the development of clinically actionable biomarkers and more personalized immunotherapeutic approaches and novel risk-adapted treatment strategies in MM.

Immuno

8 October 2026

Bone Marrow Microenvironment (BMME) in multiple myeloma: Schematic representation of the bone marrow microenvironment in multiple myeloma, highlighting the bidirectional interactions between malignant plasma cells and surrounding cellular and non-cellular compartments. Bone marrow stromal cells, tumor-associated macrophages, myeloid-derived suppressor cells, regulatory T cells, endothelial cells, osteoclasts, osteoblasts, cytotoxic CD8+ T cells, and natural killer cells contribute to tumor growth, immune evasion, bone remodeling, angiogenesis, metabolic adaptation, and therapeutic resistance. The supportive non-cellular niche includes extracellular matrix, extracellular vesicles, soluble cytokines and chemokines, hypoxia-related signaling, and reactive oxygen species.
  • Article
  • Open Access

Background: Antisperm antibodies (ASA) are recognized as a potential immunological factor in male infertility; however, their prevalence and clinical correlates remain incompletely characterized in Middle Eastern populations. This study aimed to estimate the prevalence of clinically significant ASA positivity and investigate its associations with demographic, clinical, and semen characteristics among infertile men in Erbil, Kurdistan Region of Iraq. Methods: A multicenter retrospective cross-sectional study was conducted between July 2025 and March 2026 at urology and fertility centers in Erbil. A total of 465 infertile men were included after predefined data cleaning and MAR-test reclassification procedures. Demographic, clinical, and semen parameters were collected, and ASA status was assessed using the direct mixed antiglobulin reaction (MAR) test. Clinically significant positivity was defined as antibodies bound to ≥50% of motile spermatozoa. Associations between ASA status and participant characteristics were examined using bivariate and multivariable analyses. Additional exploratory analyses included k-means clustering of semen profiles and Random Forest machine-learning modelling to evaluate predictors of ASA positivity. Results: ASA positivity was identified in 53 of 465 participants, yielding a prevalence of 11.4% (95% CI: 8.7–14.7%). No significant associations were observed between ASA positivity and residence, smoking status, varicocele, infertility type, nutritional supplement use, sperm concentration, progressive motility, non-progressive motility, or sperm morphology (all p > 0.05). Men with secondary infertility demonstrated a modestly higher median ASA percentage than those with primary infertility; however, binary ASA positivity did not differ significantly between groups. Multivariable logistic regression showed limited explanatory capacity (AUC = 0.607), while a Random Forest classifier achieved only marginal discrimination on the test dataset (AUC = 0.567). Clustering analysis identified two distinct semen-quality phenotypes, but ASA prevalence did not differ significantly between clusters. Conclusions: Clinically significant ASA positivity was present in approximately one in nine infertile men attending participating centers in Erbil. Routine demographic, clinical, and semen characteristics were poor predictors of ASA status, and neither conventional statistical modelling nor machine-learning approaches reliably identified ASA-positive individuals. These findings suggest that ASA-associated infertility may not be adequately captured by standard infertility assessments alone and support the selective use of direct ASA testing within comprehensive male infertility evaluation. Larger prospective studies incorporating fertile controls, detailed reproductive histories, complementary antibody assays, and immunological biomarkers are warranted.

Immuno

3 October 2026

Antisperm antibody (ASA) status distribution in the study cohort (n = 465). ASA positivity was defined as ≥50% of motile spermatozoa bearing antibodies on the Direct Mixed Antiglobulin Reaction (MAR) test. Following data cleaning and reclassification, 53 men (11.4%; 95% CI 8.7–14.7%) were ASA positive and 412 (88.6%) were ASA negative.
  • Case Report
  • Open Access

Immune-mediated necrotizing myopathy (IMNM) is an exceptionally uncommon variant of idiopathic inflammatory myopathies (IIMs). Statins have been linked to a range of muscle-related side effects described as statin-associated muscle symptoms (SAMS), including IMNM, which is triggered by anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies. We present a case involving a 93-year-old woman who had been using statins for over two decades and exhibited progressive muscle weakness, predominantly proximal rather than distal, along with elevated serum creatine kinase levels, notable denervation on electromyography, and myopathic motor unit action potentials, leading to her diagnosis of anti-HMGCR-induced IMNM. Her condition was extremely severe, rendering her completely dependent on others and confined to bed. Throughout her illness, she underwent treatment with glucocorticoids, intravenous immunoglobulin (IVIG), mycophenolate mofetil (MMF), and a low-dose induction of rituximab (RTX). Additionally, she was diagnosed with subclinical hypothyroidism, which may have contributed to her heightened susceptibility to statin-induced IMNM. She developed severe pneumonia and a urinary tract infection, along with septic shock, after being off immunosuppressive medications for about two months following a low-dose rituximab infusion. Unfortunately, she passed away before the minimum expected duration for meaningful recovery had elapsed. This case underscores the necessity of considering anti-HMGCR-induced IMNM in patients who are using statins. Reporting this uncommonly observed, very late-onset, and rare SAMS aims to enhance awareness among healthcare providers treating individuals with dyslipidemia and other atherosclerotic conditions who require statin therapy.

Immuno

30 September 2026

Electromyography findings (each square representing 50 µv voltage on the y-axis and 10 ms duration on the x-axis). (a) Abnormal spontaneous activity when the muscle is at rest; positive sharp waves in the tibialis anterior muscle. (b) Short-duration and polyphasic myopathic motor unit action potential upon activation in the deltoid muscle.
  • Review
  • Open Access

Post-Dengue Syndrome: From Immunopathogenesis to Multisystemic Clinical Sequelae

  • Alexis Hipólito García,
  • Francis Crespo and
  • Juan Bautista De Sanctis
  • + 3 authors

Dengue virus (DENV) causes the most prevalent arboviral infection worldwide. Although classically regarded as an acute illness, growing evidence describes Post-Dengue Syndrome (PDS) as a chronic entity affecting a subset of patients, with pooled estimates placing post-infectious fatigue at 20.0% (95% CI 10–36) and no standardized case definition yet available. This narrative review analyzes its pathophysiology: the cytokine storm, antibody-dependent enhancement, and NS1-triggered molecular mimicry, together with the cells that execute them—dendritic cells, mononuclear phagocytes, NK cells, platelets, and complement on the innate side, and plasmablast expansion, follicular helper T cell activation, defective regulatory control, and PD-L1/PD-1-mediated exhaustion on the adaptive side. Almost all of these immunological mechanisms have been characterized during acute infection; few studies have sampled the same patients during convalescence, and even fewer have compared those who developed persistent symptoms with those who recovered. They are therefore established features of acute dengue and, at present, hypotheses about PDS rather than demonstrated features. Genetic susceptibility is examined through polymorphisms of HLA, FcγRIIa, Toll-like receptor, and cytokine genes. Multisystemic manifestations are described—persistent fatigue, fibromyalgia-like myalgia and arthralgia, alopecia, brain fog, and mood disturbance—alongside neurological complications, categorized into direct neuroinvasion and post-infectious immune-mediated damage such as Guillain–Barré syndrome and encephalomyelitis. Recent population-based data linking dengue to acute neurological events and to later cognitive decline are examined critically, as is the unsettled question of whether post-dengue neuroinflammation amounts to neurodegeneration. Finally, the authors address the influence of age and sex and outline therapeutic and research priorities, offering an immunoclinical perspective for the multidisciplinary management of these patients.

Immuno

29 September 2026

Integrated model of Post-Dengue Syndrome (PDS) pathogenesis, from acute infection to persistent disease. Left panel, acute phase (0–2 weeks): following the mosquito bite, non-neutralizing immunoglobulin G (IgG) from a previous heterotypic infection binds dengue virus (DENV) and promotes antibody-dependent enhancement (ADE) through the Fc gamma receptor (FcγR) in monocytes and macrophages, amplifying replication; the resulting cytokine storm—interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ)—together with the release of circulating non-structural protein 1 (NS1) antigen, disrupts the endothelial barrier and produces vascular leakage. Center panel, immunopathogenic bridge (weeks to months): antibodies directed against NS1 (anti-NS1) and against the viral envelope protein (anti-E) recognize epitopes shared with host structures, generating autoreactivity against endothelial cells and platelets; in parallel, memory B cells persist, and T cells acquire an exhausted phenotype in which engagement of programmed cell death protein 1 (PD-1) by its ligand (PD-L1) limits cytotoxic function. Host modulators—human leukocyte antigen (HLA) polymorphisms (HLA-A*24, HLA-DRB1*11) and the histidine/histidine variant at position 131 of the Fc gamma receptor IIa (FcγRIIa HH131)—act on the amplitude of these events rather than on any single one of them. Right panel, Post-Dengue Syndrome (beyond six months): the clinical expression of the process, comprising chronic fatigue, fibromyalgia-like symptoms and arthralgia, alopecia, mood disturbance, blood–brain barrier (BBB) disruption with neuroinflammation and brain fog, and immune-mediated neurological complications such as Guillain–Barré syndrome (GBS). Solid arrows denote the temporal progression and the mechanisms established in patients; dashed arrows denote proposed relationships inferred from acute-phase data but not demonstrated during convalescence.

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Immuno - ISSN 2673-5601