Journal Description
Immuno
Immuno
is an international, peer-reviewed, open access journal on immunological research and clinical applications published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within ESCI (Web of Science), Scopus, EBSCO, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 31.6 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the first half of 2025).
- Journal Rank: CiteScore - Q2 (Medicine (miscellaneous))
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Impact Factor:
2.5 (2024);
5-Year Impact Factor:
2.0 (2024)
Latest Articles
Cold and Cholinergic Urticaria: Predictors of Anaphylaxis and Therapeutic Approaches—What We Know and What We Do Not Know?
Immuno 2025, 5(4), 44; https://doi.org/10.3390/immuno5040044 - 23 Sep 2025
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Inducible forms of chronic urticaria are characterized by an early age of onset and a long duration of disease. In addition, cold and cholinergic urticaria have a risk of developing systemic, sometimes life-threatening, reactions. Determining the pathogenetic mechanisms and laboratory and clinical predictors
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Inducible forms of chronic urticaria are characterized by an early age of onset and a long duration of disease. In addition, cold and cholinergic urticaria have a risk of developing systemic, sometimes life-threatening, reactions. Determining the pathogenetic mechanisms and laboratory and clinical predictors of their development is an open question in the understanding of these diseases. This literature review demonstrates the current known facts that allow the identification of patients with cold and cholinergic urticaria in high-risk groups of anaphylaxis development and, therefore, the possibility to prevent emergency situations and to manage them in time. For cold and cholinergic urticaria, observations of Kounis syndrome–acute coronary syndrome (myocardial infarction or unstable angina) have been described. A series of trials, including the large international multicenter COLD-CE study of anaphylaxis in cold urticaria, have identified early age of urticaria onset, severe clinical symptoms, shortening of the critical temperature threshold, comorbid bronchial asthma, concomitant angioedema, and pruritus of the earlobes as warning signs. No such large-scale studies have been conducted for cholinergic urticaria. Among the few high-risk factors for systemic reactions in cholinergic urticaria described in the literature is the occurrence of angioedema. Thus, it is possible to identify some patients in the high-risk group already at the stage of initial anamnesis collection, and additional data can be collected during the examination. Laboratory biomarkers, clinical predictors, understanding the mechanisms of anaphylaxis by physical triggers or their consequences, and optimal options for pathogenetic therapy are still unresolved issues that require further research. The aim of this review is to provide a content analysis of current knowledge about chronic inducible urticarias in order to increase clinicians’ awareness and, consequently, reduce the risk of urgent conditions associated with them.
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Open AccessArticle
The Role of CD68+ Cells in Bronchoalveolar Lavage Fluid for the Diagnosis of Respiratory Diseases
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Igor D. Zlotnikov, Natalia I. Kolganova, Shamil A. Gitinov, Dmitry Y. Ovsyannikov and Elena V. Kudryashova
Immuno 2025, 5(3), 43; https://doi.org/10.3390/immuno5030043 - 22 Sep 2025
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Addressing the critical challenge in the differential diagnosis of severe inflammatory lung diseases, we propose a novel methodology for the analysis of macrophage surface receptors, CD68 and CD206, using specific non-antibody ligands. We developed a non-antibody alternative for the fluorometric detection of CD68+
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Addressing the critical challenge in the differential diagnosis of severe inflammatory lung diseases, we propose a novel methodology for the analysis of macrophage surface receptors, CD68 and CD206, using specific non-antibody ligands. We developed a non-antibody alternative for the fluorometric detection of CD68+ cells, focusing on macrophages as key functional markers in inflammatory processes. Our marker based on dioleylphosphatidylserine (DOPS), a specific ligand to CD68, was incorporated into a liposomal delivery system. The specificity of this DOPS-based ligand can be precisely modulated by the liposome’s composition and the polyvalent presentation of the ligand. We synthesized a series of fluorescently-labeled DOPS-based ligands and developed a liposome-based sandwich fluorometric assay. This assay enables the isolation and quantification of CD68 receptor presence from bronchoalveolar lavage fluid (BALF). The results confirmed the specific binding of DOPS/lecithin liposomes to CD68+ cells compared to control lecithin systems. Furthermore, the incorporation of PEGylated ‘stealth’ liposomes significantly enhanced binding specificity and facilitated the generation of distinct binding profiles, which proved valuable in differentiating various inflammatory conditions. This approach yielded unique binding profiles of PS-based ligands to CD68+ cells, which varied significantly among a broad range of respiratory conditions, including primary ciliary dyskinesia, bronchial asthma, bronchitis, bacterial infection, pneumonia, and bronchiectasis. Confocal Laser Scanning Microscopy demonstrated selective binding and intracellular localization of the DOPS-based marker within CD68+ macrophages from BALF samples of patients with bronchitis or asthma. The binding parameters of this multivalent composite ligand with the CD68 receptor are comparable to those of antibodies. The inherent binding specificity of phosphatidylserine may offer a sufficient and viable alternative to conventional antibodies. Our results demonstrate the remarkable potential of this novel DOPS-based assay as a complementary tool for the developing non-antibody-based systems for the differential diagnosis of the respiratory diseases, warranting further investigation in larger clinical studies.
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Open AccessArticle
Myostatin Regulates Inflammatory Cytokine and Chemokine Expression, Rheumatoid Arthritis Synovial Fibroblast Invasion, and CD4+ Th Cell Transmigration
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Samudra Lansakara, Janis Weis, Chathura Siriwardhana and Yongsoo Kim
Immuno 2025, 5(3), 42; https://doi.org/10.3390/immuno5030042 - 19 Sep 2025
Abstract
Rheumatoid arthritis synovial fibroblasts (RASFs) play a pivotal role in joint destruction in RA. Myostatin (MSTN), a myokine, is highly expressed in the RA synovium; however, its role in the function of RASFs is unclear. We hypothesized that MSTN amplifies inflammatory cytokines/chemokines, promotes
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Rheumatoid arthritis synovial fibroblasts (RASFs) play a pivotal role in joint destruction in RA. Myostatin (MSTN), a myokine, is highly expressed in the RA synovium; however, its role in the function of RASFs is unclear. We hypothesized that MSTN amplifies inflammatory cytokines/chemokines, promotes RASF invasion, and facilitates CD4+ Th cell transmigration. Immortalized MH7A cells (RASFs) and healthy synovial fibroblasts (HSFs) were treated with MSTN (0, 10, 20 ng/mL) for 0, 24, and 48 h. Cytokines (IL-8, IL-17, TNF-α, IL-6, IL-23, IFN-γ, IFN-β) and chemokines (CCL2, CCL20, CXCL13, CXCL1) were quantified by ELISA, RT-qPCR, and Western blotting. To evaluate MSTN regulation, cells were treated with pro-inflammatory mediators (TNF-α, IL-17, IFN-γ, IFN-β, CCL2, CXCL1). MSTN’s effects on Thy-1(CD90)+ RASF/HSF proliferation, RASF invasion, and CD4+ T-cell transmigration were assessed. Compared with HSFs, RASFs exhibited greater proliferative activity. MSTN significantly upregulated cytokines/chemokines, with CXCL1 showing the strongest induction in RASFs. IFN-γ and IL-17 robustly increased MSTN expression, indicating a feed-forward loop. MSTN did not alter Thy-1(CD90)+ fibroblast proliferation but significantly enhanced RASF invasion and CD4+ T-cell transmigration. Neutralizing CXCL1 or IL-17 reduced transmigration, with stronger inhibition via CXCL1. These findings offer new insights into the role of MSTN in RA pathogenesis and highlight its potential as a therapeutic target.
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(This article belongs to the Special Issue The Role of Cytokines and Autoantibodies Against Cytokines in Health and Disease)
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Open AccessReview
A Scoping Review of Clinical, Genetic, and Mechanistic Evidence Linking IL-6/IL-6R Signaling and Type 1 Diabetes Mellitus
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Ryuichi Ohta, Taichi Fujimori, Chiaki Sano and Kunihiro Ichinose
Immuno 2025, 5(3), 41; https://doi.org/10.3390/immuno5030041 - 19 Sep 2025
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Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune-mediated β-cell destruction, where interleukin-6 (IL-6) signaling plays a complex and context-dependent role. Tocilizumab, an IL-6 receptor (IL-6R) inhibitor, is effective in several autoimmune conditions, but its influence on the onset and
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Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune-mediated β-cell destruction, where interleukin-6 (IL-6) signaling plays a complex and context-dependent role. Tocilizumab, an IL-6 receptor (IL-6R) inhibitor, is effective in several autoimmune conditions, but its influence on the onset and progression of T1DM remains uncertain. This scoping review aimed to map current clinical, genetic, and mechanistic evidence linking IL-6/IL-6R signaling to T1DM risk and to identify key research gaps. Following PRISMA-ScR guidelines, PubMed, Embase, and Web of Science were searched for studies from 2005 to 2025 reporting associations between tocilizumab or IL-6R modulation and T1DM onset. Six studies were included: one case report describing T1DM onset during tocilizumab therapy in a genetically predisposed patient, one randomized controlled trial showing no significant β-cell preservation with tocilizumab, three Mendelian randomization analyses with conflicting findings on IL-6R signaling, and one mechanistic study showing enhanced IL-6 responsiveness in early-stage T1DM. Collectively, evidence remains fragmented and inconclusive, highlighting research gaps in the differential roles of IL-6 classic versus trans-signaling and the impact of genetic predisposition. Future prospective studies should clarify whether selective IL-6 trans-signaling blockade may offer safer, targeted strategies for modulating autoimmune β-cell destruction.
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Open AccessReview
Immune Landscape of Intrahepatic Cholangiocarcinoma: Evasion and Therapeutic Insights
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Nunzia Porro, Elena Spínola-Lasso, Fabio Marra and Alessandra Gentilini
Immuno 2025, 5(3), 40; https://doi.org/10.3390/immuno5030040 - 17 Sep 2025
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Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive and heterogeneous malignancy characterized by marked resistance to standard chemotherapy and poor prognosis. While the advent of immunotherapy has revolutionized the management of several solid tumors, including melanoma, breast cancer, and non-small cell lung cancer, its
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Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive and heterogeneous malignancy characterized by marked resistance to standard chemotherapy and poor prognosis. While the advent of immunotherapy has revolutionized the management of several solid tumors, including melanoma, breast cancer, and non-small cell lung cancer, its efficacy in iCCA remains limited. Recent clinical trials have demonstrated the efficacy of durvalumab in combination with chemotherapy for iCCA, leading to its approval as a first-line treatment. However, overall response rates remain low, largely due to its immunosuppressive tumor immune microenvironment (TIME). The immune-cold nature of iCCA is typified by a dominant presence of immunosuppressive cell populations, including M2-polarized tumor-associated macrophages, myeloid-derived suppressor cells, and T regulatory cells. In addition, traditional biomarkers such as PD-L1 expression, tumor mutational burden, and microsatellite instability have shown limited predictive value in iCCA, highlighting the need for novel biomarkers and immunotherapeutic strategies. Emerging approaches aimed at reprogramming the TIME, including combination therapies targeting suppressive cells, stromal remodeling, and novel immune effectors like CAR-T and cancer vaccines, hold significant promise for enhancing therapeutic efficacy. This review summarizes the distinct features of iCCA TIME, key mechanisms of immune evasion, current challenges, and future directions to overcome immune resistance, with the aim of developing personalized immunotherapies to improve patient outcomes.
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(This article belongs to the Special Issue New Insights of Anti-cancer Immunity and Cancer Immune Evasion)
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Open AccessArticle
The Effects of Time-Restricted Eating and Alternate-Day Modified Fasting on Interferon-γ and Interleukin-10 Levels in Young Asian Women with Obesity: A Quasi-Experimental Study
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Chy’as Diuranil Astrid Permataputri, Purwo Sri Rejeki, Raden Argarini, Shariff Halim, Sheeny Priska Purnomo and Dian Aristia Rachmayanti
Immuno 2025, 5(3), 39; https://doi.org/10.3390/immuno5030039 - 17 Sep 2025
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Background/Objectives: Obesity induces chronic low-grade inflammation marked by elevated pro-inflammatory cytokines, such as interferon-gamma (IFN-γ), and reduced anti-inflammatory cytokines like interleukin-10 (IL-10), contributing to immune dysregulation. Intermittent fasting (IF) may restore immune balance through metabolic and circadian mechanisms. This study compared the
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Background/Objectives: Obesity induces chronic low-grade inflammation marked by elevated pro-inflammatory cytokines, such as interferon-gamma (IFN-γ), and reduced anti-inflammatory cytokines like interleukin-10 (IL-10), contributing to immune dysregulation. Intermittent fasting (IF) may restore immune balance through metabolic and circadian mechanisms. This study compared the effects of time-restricted eating (TRE) and alternate-day modified fasting (ADMF) on IFN-γ and IL-10 levels in young women with obesity. Methods: A 20-day quasi-experimental study with a pretest–posttest control group design included 23 non-diabetic women with obesity (aged 18–25 years; BMI ≥ 25 kg/m2 according to the Asia-Pacific classification), randomized into control (n = 8), TRE 18:6 (n = 8), and ADMF (n = 7) groups. IFN-γ and IL-10 serum levels were measured pre- and post-intervention using ELISA kits. Results: TRE significantly reduced IFN-γ levels (p = 0.025), while no significant change was observed in the ADMF or control groups. No significant changes were found in IL-10 levels. Conclusions: TRE effectively reduced pro-inflammatory IFN-γ levels without significantly altering anti-inflammatory IL-10 levels, suggesting an anti-inflammatory effect primarily mediated through suppression of IFN-γ rather than IL-10 upregulation. The absence of significant IL-10 changes may reflect complex immunoregulatory dynamics in obesity. ADMF showed no significant immunomodulatory impact. These findings support TRE as a promising non-pharmacologic strategy to attenuate inflammation and improve immune balance in young women with obesity.
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Open AccessReview
The Role of IL28B Polymorphism in Regulating Innate and Adaptive Immunity Against Viral Infection Among Allogenic Stem Cells Transplant Recipients
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Mohamed A. Eltokhy, Bhaumik Patel, Marina Curcic, Faizah Alabi, Shadan Modaresahmadi, Omar Eltoukhy, Esraa G. Abdelmageed and Sahar Radwan
Immuno 2025, 5(3), 38; https://doi.org/10.3390/immuno5030038 - 3 Sep 2025
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Viral infection is a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), largely due to its impact on and interaction with immune reconstitution. Both innate and adaptive immunity are essential for effective viral control, yet their recovery post-transplant
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Viral infection is a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), largely due to its impact on and interaction with immune reconstitution. Both innate and adaptive immunity are essential for effective viral control, yet their recovery post-transplant is often delayed or functionally impaired. Emerging evidence suggests genetic variation, particularly polymorphisms in the IL28B gene (encoding IFN-λ3), as a critical factor influencing the quality and timing of immune responses during the early post-transplant period. This review explores the role of IL28B polymorphisms in shaping antiviral immunity, in general, as well as after Allo-HSCT. IL28B variants have been implicated in modulating interferon-stimulated gene (ISG) expression, natural killer (NK) cell activity, and type I/III interferon signaling, all central components of innate immune defense against viral infections. Furthermore, IL28B polymorphisms, particularly rs12979860, have been shown in both general populations and limited HSCT cohorts to alter T cell response and interferon production, affecting reactivation and clearance of multiple viruses such as cytomegalovirus (CMV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein–Barr virus (EBV), COVID-19, and BK polyomavirus (BKPyV) as well as Graft vs. Host disease, thereby affecting adaptive immune reconstitution and long-term viral control. Understanding how IL28B genotype alters immune dynamics in transplant recipients could enhance risk stratification for CMV and other diseases and inform personalized prophylactic or therapeutic strategies. Therefore, this review highlights IL28B as a promising biomarker and potential immunoregulatory target in the management of viral infection post-Allo-HSCT.
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Open AccessArticle
RIPK2 Inhibition Blocks NOD2-Mediated IL-1β Production by Macrophages In Vitro but Exacerbates Crohn’s Disease-like Ileitis in SHIP–/– Mice
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Yvonne C. F. Pang, Wei Jen Ma, Susan C. Menzies and Laura M. Sly
Immuno 2025, 5(3), 37; https://doi.org/10.3390/immuno5030037 - 29 Aug 2025
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Crohn’s disease is a chronic, idiopathic inflammatory bowel disease characterized by patchy, transmural inflammation that is influenced by genetic, environmental, and microbial factors. The NOD2 pathway mediates NFκB activation and pro-inflammatory cytokine production. In the SHIP–/– murine model of Crohn’s disease-like ileitis, macrophage-derived
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Crohn’s disease is a chronic, idiopathic inflammatory bowel disease characterized by patchy, transmural inflammation that is influenced by genetic, environmental, and microbial factors. The NOD2 pathway mediates NFκB activation and pro-inflammatory cytokine production. In the SHIP–/– murine model of Crohn’s disease-like ileitis, macrophage-derived IL-1β production drives intestinal inflammation. SHIP reduces NOD2 signaling by preventing downstream interaction between RIPK2 and XIAP, leading us to hypothesize that blocking RIPK2 in SHIP–/– mice would ameliorate intestinal inflammation. We examined the effects of RIPK2 inhibition on pro-inflammatory cytokine production in SHIP+/+ and SHIP–/– macrophages and in mice, using the RIPK2 inhibitor, GSK2983559. We found that GSK2983559 blocked RIPK2 activation in SHIP+/+ and SHIP–/– bone marrow-derived macrophages (BMDMs), and reduced Il1b transcription and IL-1β production in (MDP+LPS)-stimulated SHIP–/– BMDMs. Despite the reduction of IL-1β production in BMDMs, in vivo treatment with GSK2983559 worsened intestinal inflammation and increased IL-1β concentrations in the ileal tissues of SHIP–/– mice. GSK2983559 only modestly reduced IL-1β in (MDP+LPS)-stimulated SHIP–/– peritoneal macrophages, and did not suppress pro-inflammatory cytokine production in response to TLR ligands in peritoneal macrophages from either SHIP+/+ or SHIP–/– mice. Taken together, our data suggest that although RIPK2 inhibition can block IL-1β production by (MDP+LPS)-stimulated macrophages in vitro, it is not an effective anti-inflammatory strategy in vivo, highlighting the limitations of targeting RIPK2 to treat intestinal inflammation in the context of SHIP deficiency.
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(This article belongs to the Section Innate Immunity and Inflammation)
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Open AccessReview
Olive Oil Polyphenols in Cancer: Molecular Mechanisms and Therapeutic Promise
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Bashar Saad and Abdalsalam Kmail
Immuno 2025, 5(3), 36; https://doi.org/10.3390/immuno5030036 - 26 Aug 2025
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Olive oil, a cornerstone of the Mediterranean diet, is increasingly recognized not only for its cardiovascular benefits but also for its potential role in cancer prevention and therapy. Among its bioactive constituents, several phenolic compounds—tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal—have demonstrated promising anticancer
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Olive oil, a cornerstone of the Mediterranean diet, is increasingly recognized not only for its cardiovascular benefits but also for its potential role in cancer prevention and therapy. Among its bioactive constituents, several phenolic compounds—tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal—have demonstrated promising anticancer activities in various experimental models. These compounds act synergistically through diverse mechanisms, including antioxidant, anti-inflammatory, and immunomodulatory effects, as well as modulation of cell proliferation, apoptosis, angiogenesis, and metastasis. Notably, oleocanthal selectively induces cancer cell death via lysosomal membrane permeabilization, while hydroxytyrosol and oleuropein exhibit potent radical-scavenging and anti-proliferative properties. This review synthesizes findings from in vitro, in vivo, and clinical studies on the anticancer potential of these polyphenols, with emphasis on their mechanisms of action and possible applications in cancer prevention and adjunctive therapy. Given the established link between obesity and cancer development, clinical studies examining the metabolic, anti-inflammatory, and immunomodulatory effects of olive polyphenols in populations with obesity or prediabetes provide valuable insights into their potential to influence cancer-related pathways indirectly. However, direct clinical evidence in cancer patients remains limited and preliminary, underscoring the need for focused, well-controlled trials with cancer-specific endpoints. Furthermore, it critically evaluates the translational relevance of these findings, highlighting gaps in clinical research and future directions. Literature was retrieved from Google Scholar, PubMed, and ScienceDirect using keywords such as cancer, immunomodulatory, anti-inflammatory, olive, tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal. Given the rising global cancer burden and the favorable safety profiles of these natural molecules, elucidating their molecular actions may support the development of novel integrative therapeutic strategies.
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(This article belongs to the Section Cancer Immunology and Immunotherapy)
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Open AccessArticle
Immunophenotyping and Functional Characterization of NK Cells in SARS-CoV-2 Infection
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Steliyan Petrov, Martina Bozhkova, Mariya Ivanovska, Teodora Kalfova, Alexandra Baldzhieva, Angel Todev, Dilyana Kirova, Yoana Kicheva, Stoyno Stoynov, Marianna Murdjeva and Hristo Taskov
Immuno 2025, 5(3), 35; https://doi.org/10.3390/immuno5030035 - 15 Aug 2025
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The immune response to SARS-CoV-2 infection involves significant alterations in the phenotype and function of natural killer (NK) cells. This study aimed to investigate the dynamic changes in NK cell subsets during COVID-19 by analyzing their activation and inhibitory markers [CD3, CD14, CD16,
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The immune response to SARS-CoV-2 infection involves significant alterations in the phenotype and function of natural killer (NK) cells. This study aimed to investigate the dynamic changes in NK cell subsets during COVID-19 by analyzing their activation and inhibitory markers [CD3, CD14, CD16, CD19, CD25, CD45, CD56, CD57, CD69, CD159a (NKG2A), CD159c (NKG2C), CD314 (NKG2D), CD335 (NKp46)], cytotoxic potential (perforin, interferon-gamma, granzyme B), and direct cytotoxicity against a newly genetically modified K562 cell line. Peripheral blood samples were collected from COVID-19 patients on days 3–5 and day 30 post-symptom onset and were compared to healthy controls. 16-color flow cytometry analysis revealed distinct shifts in NK cell subpopulations, characterized by increased expression of the inhibitory receptor NKG2A and the activating receptors NKG2D and NKG2C, particularly in the CD56+CD16− subset. Elevated IFN-γ production on day 30 suggested a recovery-phase immune response, while the persistent upregulation of NKG2A indicated an ongoing regulatory mechanism. The CD16+CD56− subpopulation exhibited increased expression of the markers CD69 and CD25 over time; however, its cytotoxic potential, assessed through granzyme B levels and direct cytotoxicity assays, remained lower than that of healthy controls. Significant correlations were observed between CD57 and CD69 expression, as well as NKp46 and IFN-γ production, highlighting a coordinated balance between activation and regulatory mechanisms. These findings suggest that NK cells undergo functional adaptation during COVID-19, displaying signs of partial exhaustion while retaining antiviral potential. Understanding the interplay between NK cell activation and suppression may provide valuable insights into immune dysregulation in COVID-19 and inform potential therapeutic interventions.
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(This article belongs to the Section Innate Immunity and Inflammation)
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Open AccessHypothesis
Metal Pollution as a Risk Factor for HIV Infection
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Joel Henrique Ellwanger, Jacqueline María Valverde-Villegas, Marina Ziliotto and José Artur Bogo Chies
Immuno 2025, 5(3), 34; https://doi.org/10.3390/immuno5030034 - 11 Aug 2025
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The human C-C chemokine receptor type 5 (CCR5) is a molecule primarily expressed on the surface of inflammatory cells, acting as the main HIV co-receptor. In order to penetrate host cells, HIV interacts with both CCR5 and the CD4 molecule during the infectious
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The human C-C chemokine receptor type 5 (CCR5) is a molecule primarily expressed on the surface of inflammatory cells, acting as the main HIV co-receptor. In order to penetrate host cells, HIV interacts with both CCR5 and the CD4 molecule during the infectious process. Emerging evidence suggests that pollution by metals, such as aluminum, lead, and manganese, triggers CCR5-mediated inflammation, which may have important implications for the risk of HIV infection. Specifically, we hypothesize that exposure to pollution by metals causes inflammation and elevated CCR5 expression on the surface of CD4+ cells, resulting in an increased risk of HIV infection. Our hypothesis is supported by toxicogenomic data, which shows that both air pollutants and some metals (e.g., arsenic, cadmium, nickel) induce CCR5 expression. Finally, approaches to evaluate the hypothesis are suggested. If confirmed, our hypothesis introduces environmental pollution to the set of biological factors influencing the risk of HIV infection.
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Open AccessArticle
Impact of Major Pelvic Ganglion Denervation on Prostate Histology, Immune Response, and Serum Prolactin and Testosterone Levels in Rats
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Pabeli Saraí Becerra-Romero, Cynthia Fernández-Pomares, Juan Carlos Rodríguez-Alba, Jorge Manzo, Gonzalo E. Aranda-Abreu, Fausto Rojas-Durán, Deissy Herrera-Covarrubias, María Rebeca Toledo-Cárdenas, Genaro Alfonso Coria-Ávila and Maria Elena Hernández-Aguilar
Immuno 2025, 5(3), 33; https://doi.org/10.3390/immuno5030033 - 6 Aug 2025
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The prostate gland, a male accessory reproductive organ, is regulated by hormonal inputs and autonomic innervation from the major pelvic ganglion. This study examined the effects of major pelvic ganglion denervation on prostate histology, immune cell infiltration, and systemic levels of prolactin, testosterone,
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The prostate gland, a male accessory reproductive organ, is regulated by hormonal inputs and autonomic innervation from the major pelvic ganglion. This study examined the effects of major pelvic ganglion denervation on prostate histology, immune cell infiltration, and systemic levels of prolactin, testosterone, and cytokines in rats. Male Wistar rats (300–350 g) were divided into groups receiving bilateral axotomy of the hypogastric nerve, the pelvic nerve, or both, alongside with a sham-operated control. After 15 days, the animals were killed, and prostate tissue was dissociated in DMEM medium containing DNase I and collagenase. The dissociated cells were stained with fluorochrome-conjugated antibodies, and cell characterization was performed using a flow cytometer. Hematoxylin and eosin (H&E) staining was used to analyze histological characteristics, while testosterone, prolactin, and interleukin levels were measured via ELISA. Histological analysis revealed inflammatory atypical hypertrophy e hiperplasia. Immunological assessments demonstrated increased leukocytes, T lymphocytes (CD4+ and CD8+), B lymphocytes, and macrophages following double nerve axotomy. Serum analyses showed elevated pro-inflammatory cytokines IL-1β, IL-6, and IFN-γ, as well as anti-inflammatory IL-10, in denervated animals. Hormonal assessments revealed significant increases in serum prolactin and testosterone levels after double axotomy. Loss of neural control may promote pathological prostate changes via inflammation and hormonal dysregulation, offering insights into neuroimmune and neuroendocrine mechanisms underlying prostate pathologies.
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Open AccessReview
Cancer Resistance to Immunotherapy
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Rita Khoury, Annoir Shayya, Cendrella Bou Orm, Osama Zein Deen and Hady Ghanem
Immuno 2025, 5(3), 32; https://doi.org/10.3390/immuno5030032 - 5 Aug 2025
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Immunotherapy has revolutionized cancer treatment. Despite its success across various malignancies, a significant proportion of patients either fail to respond (primary resistance) or relapse after an initial response (acquired resistance). This review explores the different mechanisms underlying resistance to immunotherapy, including tumor-intrinsic factors
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Immunotherapy has revolutionized cancer treatment. Despite its success across various malignancies, a significant proportion of patients either fail to respond (primary resistance) or relapse after an initial response (acquired resistance). This review explores the different mechanisms underlying resistance to immunotherapy, including tumor-intrinsic factors such as loss of antigen presentation, genetic, and epigenetic mutations. It also examines tumor-extrinsic contributors, such as immunosuppressive cells in the tumor microenvironment, checkpoint molecule upregulation, and microbiome influences. A comprehensive understanding of resistance mechanisms is essential for improving patient selection, developing combination therapies, and ultimately enhancing the efficacy and durability of immunotherapeutic interventions.
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Open AccessReview
Etiopathogenesis and Treatment of Colorectal Cancer
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Mayara Bocchi, Eduardo Vignoto Fernandes, Nathália de Sousa Pereira and Marla Karine Amarante
Immuno 2025, 5(3), 31; https://doi.org/10.3390/immuno5030031 - 4 Aug 2025
Abstract
Human colorectal cancer (CRC) encompasses tumors affecting a segment of the large intestine (colon) and rectum. It is the third most commonly diagnosed malignancy and the second leading cause of cancer deaths worldwide. It is a multifactorial disease, whose carcinogenesis process involves genetic
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Human colorectal cancer (CRC) encompasses tumors affecting a segment of the large intestine (colon) and rectum. It is the third most commonly diagnosed malignancy and the second leading cause of cancer deaths worldwide. It is a multifactorial disease, whose carcinogenesis process involves genetic and epigenetic alterations in oncogenes and tumor suppressor genes, including genes related to DNA repair. The pathogenic mechanisms are described based on the pathways of chromosomal instability, microsatellite instability, and CpG island methylator phenotype. When detected early, CRC is potentially curable, and its treatment is based on the pathological characteristics of the tumor and factors related to the patient, as well as on drug efficacy and toxicity studies. Therefore, the aim of this study was to review the pathogenesis and molecular subtypes of CRC and to describe the main targets of disease-directed therapy used in patients refractory to current treatments.
Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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Open AccessReview
EUS-Guided Pancreaticobiliary Ablation: Is It Ready for Prime Time?
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Nina Quirk, Rohan Ahuja and Nirav Thosani
Immuno 2025, 5(3), 30; https://doi.org/10.3390/immuno5030030 - 25 Jul 2025
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Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore,
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Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, it is imperative that alternative therapies are effective for non-surgical patients. There are several thermal ablative techniques, including radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), microwave ablation (MWA), alcohol ablation, stereotactic body radiotherapy (SBRT), cryoablation, irreversible electroporation (IRE), biliary intraluminal brachytherapy, and biliary photodynamic therapy (PDT). Emerging literature in animal models and human patients has demonstrated that endoscopic ultrasound (EUS)-guided RFA (EUS-RFA) prevents tumor progression through coagulative necrosis, protein denaturation, and activation of anticancer immunity in local and distant tumor tissue (abscopal effect). RFA treatment has been shown to not only reduce tumor-associated immunosuppressive cells but also increase functional T cells in distant tumor cells not treated with RFA. The remarkable ability to reduce tumor progression and promote tumor microenvironment (TME) remodeling makes RFA a very promising non-surgical therapy technique that has the potential to reduce mortality in this patient population. EUS-RFA offers superior precision and safety compared to other ablation techniques for pancreatic and biliary cancers, due to real-time imaging capabilities and minimally invasive nature. Future research should focus on optimizing RFA protocols, exploring combination therapies with chemotherapy or immunotherapy, and expanding its use in patients with metastatic disease. This review article will explore the current data and underlying pathophysiology of EUS-RFA while also highlighting the role of ablative therapies as a whole in immune activation response.
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Open AccessArticle
Immune Cell–Cytokine Interplay in NSCLC and Melanoma: A Pilot Longitudinal Study of Dynamic Biomarker Interactions
by
Alina Miruna Grecea-Balaj, Olga Soritau, Ioana Brie, Maria Perde-Schrepler, Piroska Virág, Nicolae Todor, Tudor Eliade Ciuleanu and Cosmin Andrei Cismaru
Immuno 2025, 5(3), 29; https://doi.org/10.3390/immuno5030029 - 24 Jul 2025
Abstract
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The tumor microenvironment (TME) in advanced solid tumors is determined by immune checkpoints (PD-1, CTLA-4, and CD95) and cytokine networks (IL-2, IL-10, and TNF-α) that drive CD8+ T cell exhaustion, metabolic reprogramming, and apoptosis resistance, enabling immune evasion. Some studies revealed PD-1/CD95 co-expression
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The tumor microenvironment (TME) in advanced solid tumors is determined by immune checkpoints (PD-1, CTLA-4, and CD95) and cytokine networks (IL-2, IL-10, and TNF-α) that drive CD8+ T cell exhaustion, metabolic reprogramming, and apoptosis resistance, enabling immune evasion. Some studies revealed PD-1/CD95 co-expression is a marker of T cell dysfunction, while CTLA-4 upregulation correlates with suppressed early T cell activation. IL-10 has emerged as a potential biomarker for chemoresistance and tumor aggressivity, consistent with its role in promoting anti-apoptotic signaling in cancer stem cells (CSCs). Engineered IL-2 variants and TNF-α modulation are highlighted as promising strategies to revitalize exhausted CD8+ T cells and disrupt CSC niches. This prospective single-center study investigated the dynamic TME alterations in 16 patients with immunotherapy-naïve stage IV non-small-cell lung cancer (NSCLC) and metastatic melanoma treated with anti-PD-1 nivolumab. The longitudinal immunophenotyping of peripheral blood lymphocytes (via flow cytometry) and serum cytokine analysis (via ELISA) were performed at the baseline, >3, and >6 months post-treatment to evaluate immune checkpoint co-expression (PD-1/CD95 and CTLA-4/CD8+) and the cytokine profiles (IL-2, IL-10, and TNF-α).
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Open AccessArticle
Human Gliomedin and Ryanodine 3 Type Receptor Is the Key to Explain the Guillain Barre Syndrome in SARS-CoV-2 and Others Bacterial Related to SARS-CoV-2 Postinfection? A Molecular Mimicry Point of View
by
Gustavo Alberto Obando-Pereda and Luis Alberto Ponce-Soto
Immuno 2025, 5(3), 28; https://doi.org/10.3390/immuno5030028 - 17 Jul 2025
Abstract
Guillain-Barre syndrome is an autoimmune disease that provokes neural illness causing acute paralysis neuropathy. This syndrome appears after some bacterial infections produced by Campylobacter jejuni, Streptococcus pyogenes, S. pneumoniae, Haemophilus influenciae, E. coli and current studies showed the appears
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Guillain-Barre syndrome is an autoimmune disease that provokes neural illness causing acute paralysis neuropathy. This syndrome appears after some bacterial infections produced by Campylobacter jejuni, Streptococcus pyogenes, S. pneumoniae, Haemophilus influenciae, E. coli and current studies showed the appears of this syndrome after SARS-CoV-2 infection. In this study, a in silico analysis was carry out in which to determinate bacterial epitopes than produce the molecule mimicry phenomena and that can produce the immune system activation against this epitope. A conserved amino acid sequence has been encountered with the highest probability to activate the immune system against this bacterial epitope, human gliomedin and ryanodine 3 type receptor. More studies needed to demonstrate in vivo the molecular mimicry in Guillain-Barre syndrome patients.
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(This article belongs to the Section Immunopathology and Immunohistology)
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Open AccessArticle
Next-Generation Sequencing Analysis in Greek Patients with Predominantly Antibody Deficiencies
by
Achilleas P. Galanopoulos, Sofia Raftopoulou, Styliani Sarrou, Alexia Matziri, Stamatia Papoutsopoulou, Grigorios Stratakos, Varvara A. Mouchtouri, Martin Hölzer, Christos Hadjichristodoulou, Fani Kalala and Matthaios Speletas
Immuno 2025, 5(3), 27; https://doi.org/10.3390/immuno5030027 - 16 Jul 2025
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Predominantly antibody deficiencies (PADs) are the most prevalent types of inherited errors of immunity (IEI) and are characterized by a broad range of clinical manifestations, such as recurrent infections, autoimmunity, lymphoproliferation, atopy and malignancy. The aim of this study was to identify genetic
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Predominantly antibody deficiencies (PADs) are the most prevalent types of inherited errors of immunity (IEI) and are characterized by a broad range of clinical manifestations, such as recurrent infections, autoimmunity, lymphoproliferation, atopy and malignancy. The aim of this study was to identify genetic defects associated with PADs in order to improve diagnosis and personalized care. Twenty patients (male/female: 12/8, median age of disease onset: 16.5 years, range: 1–50) were analyzed by next-generation sequencing (NGS) using a custom panel of 30 genes associated with PADs and their possible disease phenotype. The detected variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines and inheritance, and the penetrance patterns were evaluated by PCR–Sanger sequencing. Novel and rare mutations associated with the phenotype of common variable immunodeficiency (CVID) in genes encoding the transcription factors NFKB1, NFKB2 and IKZF1/IKAROS were identified. Alphafold3 protein structure prediction was utilized to perform a comprehensive visualization strategy and further delineate the mutation-bearing domains and elucidate their potential impact on protein function. This study highlights the value of genetic testing in PADs and will guide further research and improvement in diagnosis and treatment.
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Open AccessReview
Chronic Rhinosinusitis with Nasal Polyps: Window of Immunologic Responses and Horizon of Biological Therapies
by
Simin Farokhi, Seyed Mehdi Tabaie, Arshia Fakouri, Shirin Manshouri, Nikoo Emtiazi, Ayda Sanaei, Mohammad Mahjoor, Amir Mohammad Akbari, Ali Daneshvar and Farhad Seif
Immuno 2025, 5(3), 26; https://doi.org/10.3390/immuno5030026 - 11 Jul 2025
Cited by 1
Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifaceted inflammatory disorder characterized by distinct immunopathogenic entities, including type 2 inflammation mediated by cytokines such as interleukin-4 (IL-4), IL-5, and IL-13. These cytokines contribute to eosinophilic inflammation, epithelial barrier dysfunction, and mucus overproduction, resulting
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Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifaceted inflammatory disorder characterized by distinct immunopathogenic entities, including type 2 inflammation mediated by cytokines such as interleukin-4 (IL-4), IL-5, and IL-13. These cytokines contribute to eosinophilic inflammation, epithelial barrier dysfunction, and mucus overproduction, resulting in polyp formation. Advances in molecular understanding have resulted in the identification of CRSwNP endotypes, suggesting personalized treatment approaches. Conventional therapies, such as intranasal and systemic corticosteroids, provide symptom relief but are restricted by side effects and polyp recurrence, necessitating the development of novel targeted approaches. Biologic therapies represent a breakthrough in CRSwNP management. Monoclonal antibodies such as dupilumab, omalizumab, mepolizumab, and Benralizumab (IL-5 receptor alpha) target key mediators of type 2 inflammation, leading to substantial improvements in polyp size, symptom control, and quality of life. Additionally, emerging therapies like tezepelumab and brodalumab aim to address broader immune mechanisms, including type 1 and type 3 inflammation. These advancements enable tailored treatment approaches that optimize outcomes and reduce reliance on surgical interventions. Biomarker-driven research continues to refine CRSwNP classification and treatment efficacy, emphasizing precision medicine. Future efforts should focus on expanding the therapeutic landscape, investigating long-term impacts of biologics, and exploring their combinatory potential to improve disease control. This review discusses the role of innate and adaptive immunity in the pathogenesis of CRSwNP and suggests novel cytokine-targeted strategies for further considering personalized medicine in future therapeutic plans.
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(This article belongs to the Topic Skin Barrier Function and Immune Mediators as Key Therapeutic Targets of Main Inflammatory Diseases)
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Open AccessReview
Food-Specific IgG Antibodies: Decoding Their Dual Role in Immune Tolerance and Food Intolerance
by
Jenny Valentina Garmendia, Juan Bautista De Sanctis and Alexis Hipólito García
Immuno 2025, 5(3), 25; https://doi.org/10.3390/immuno5030025 - 27 Jun 2025
Abstract
IgG antibodies, particularly those of the IgG4 subclass, have generated significant debate regarding their role in immune tolerance versus food intolerance. This article comprehensively reviews the literature on the subject, exploring evidence from healthy individuals and patient populations with varied clinical conditions. On
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IgG antibodies, particularly those of the IgG4 subclass, have generated significant debate regarding their role in immune tolerance versus food intolerance. This article comprehensively reviews the literature on the subject, exploring evidence from healthy individuals and patient populations with varied clinical conditions. On one hand, IgG—especially IgG4—is frequently detected in individuals without adverse food reactions and may represent a normal adaptive immune response to constant dietary antigen exposure, contributing to the development of regulatory T-cell–mediated tolerance. On the other hand, several studies have linked elevated food-specific IgG levels with conditions characterized by increased intestinal permeability and inflammation, including eosinophilic esophagitis, irritable bowel syndrome, inflammatory bowel disease, and autoimmune disorders. The review discusses multiple investigations where IgG-guided elimination diets have yielded symptomatic improvements, suggesting a potential benefit for targeted dietary interventions. However, these findings are tempered by the observation that IgG antibodies are commonly present in asymptomatic individuals, thereby questioning their specificity as markers of adverse food reactions. Current diagnostic guidelines from leading allergy and immunology organizations discourage routine IgG testing for food allergies and intolerances, highlighting that these antibodies might instead indicate exposure or underlying inflammation rather than an actual pathogenic mechanism. There is a need for well-controlled, large-scale studies to clearly define the clinical relevance of food-specific IgG responses. Until more substantial evidence is provided, clinicians are advised to interpret the IgG results cautiously and to consider them within the broader context of each patient’s clinical presentation before recommending restrictive dietary changes.
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