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Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies, 2nd Edition

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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (30 April 2026) | Viewed by 33194

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Prof. Dr. Kinga Lis

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Department of Allergology, Clinical Immunology and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Ujejskiego 75, 85-168 Bydgoszcz, Poland
Interests: food additive; immunology; alergology
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Special Issue Information

Dear Colleagues,

Allergies and other immunity disorders are a current and deepening problem of the modern world, closely related to the progress of civilization. Although many mechanisms mediating allergic reactions have already been clearly explained, there are still many unclear mechanisms of these reactions. Also, the relationship between allergens from different sources often remains a surprising mystery. Immunodeficiency and immune disorders are also serious health problems in the modern world. The coexistence of various immune system disorders (such as allergies and immunodeficiencies) often entails diagnostic difficulties. Many times, we face the problem of our diagnostic tools being insufficient. This entails constructing new experimental laboratory methods to study the relationship between different allergens and the mechanisms of allergies and other immunologically mediated diseases. In this Special Issue, we want to focus on the mechanisms of allergic reactions, especially those atypical and accompanying immune disorders. We will try to present significant problems and difficulties related to the diagnosis of allergies, especially in unusual cases. We also want to present the possibilities of using experimental methods and laboratory protocols to study the mechanisms of allergy and cross-reactivity.

Potential topics will include:

Mechanisms of allergic reactions;
Co-factors of allergic reactions;
Unusual allergic reactions;
Allergies in immunodeficiency;
Cross-reactive allergens;
Experimental laboratory methods in allergology;
In vitro allergy diagnosis;
Biochemical properties of allergens;
New potential allergens.

You can read the publications in the first volume here:

https://www.mdpi.com/journal/cimb/special_issues/1NCDUD4Y16

Dr. Kinga Lis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Issues in Molecular Biology is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

allergy and hypersensitivity mechanisms
cross-reactivity in allergy
component resolved diagnostic (CRD)
immunodeficiencies
experimental research methods in allergology
biochemical properties of allergens

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Published Papers (7 papers)

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Research

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19 pages, 1661 KB

Open AccessArticle

The Bioactivity of Glycyrrhizae Radix et Rhizoma Praeparata cum Melle Carbon Dots: A Preliminary Study of Their Antiallergic Effect

by Siqi Wang, Xiaohan Qu, Jinye Yuan, Jihang Zhang, Jiaxuan Zhang, Xinyu Huang, Jun Wang, Ziwen An, Yue Zhang, Hui Kong, Huihua Qu and Yan Zhao

Curr. Issues Mol. Biol. 2026, 48(5), 446; https://doi.org/10.3390/cimb48050446 (registering DOI) - 24 Apr 2026

Viewed by 132

Abstract

This study concurrently addressed the separation method for carbon dots derived from Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (GRRPM) and the in vitro evaluation of their anti-allergic biological activity. Glycyrrhizae Radix et Rhizoma Praeparata cum Melle Carbon Dots (GRRPM-CDs) were prepared via decoction followed by dialysis, and their properties were characterized using High-Performance Liquid Chromatography (HPLC) and nanomaterial techniques. Anti-allergic activity was evaluated using a C48/80-induced RBL-2H3 mast cell degranulation model. Safety and efficacy were assessed using the CCK-8 assay, direct intervention, and drug-containing serum methods. The release of β-hexosaminidase (β-hex), histamine (HIS), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α) was measured by ELISA, and key proteins in the MAPK signaling pathway were analyzed by Western blot. GRRPM-CDs inhibited mast cell degranulation and the release of allergic and inflammatory mediators in a dose-dependent manner. They also significantly downregulated the phosphorylation levels of the JNK, ERK, and p38 proteins in the MAPK signaling pathway. GRRPM-CDs exhibit significant anti-allergic activity, likely via suppression of the MAPK pathway. These findings provide new insights into the bioactive components of processed Glycyrrhiza and suggest potential avenues for developing novel therapies for allergic diseases. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies, 2nd Edition)

15 pages, 3198 KB

Open AccessArticle

Conformational Flexibility of a Lipocalin Allergen (Mus m 1): Implications for Molecular Allergy Diagnostics

by Federica Agosta, Thelma A. Pertinhez, Pietro Cozzini, Alberto Spisni and Elena Ferrari

Curr. Issues Mol. Biol. 2025, 47(4), 234; https://doi.org/10.3390/cimb47040234 - 27 Mar 2025

Viewed by 1114

Abstract

Mus m 1 lipocalin is the cause of mouse allergy in sensitized individuals. The production of a soluble, stable, and immunogenic isoform of Mus m 1 is essential for developing new diagnostic tools and immunotherapeutic protocols for treating allergic symptoms. To that end, using molecular dynamics (MD), we explored the impact of substitutions at positions 120 and 138 on the structure and dynamics of the allergic isoform Mus m 1.0102. HINT-based analysis of the MD trajectories, obtained for the mutants Y120F, Y120A, C138S, and C138A, allowed the assessment of the mutations’ impact on the network of intramolecular interactions, providing insights into the mechanisms underlying protein stability, dynamics, and allergenic reactivity. The C138A mutant revealed a reduction in the solvent-accessible surface area in the region of the mutated residue, of the radius of gyration, and of the α-helix displacement from the β-barrel, features that correlate with an increase in folding stability and a satisfactory allergenic potential. We consider C138A a good candidate to be exploited for diagnostic and vaccine purposes. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies, 2nd Edition)

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17 pages, 1815 KB

Open AccessArticle

Decoding the Genetic Basis of Mast Cell Hypersensitivity and Infection Risk in Hypermobile Ehlers-Danlos Syndrome

by Purusha Shirvani, Arash Shirvani and Michael F. Holick

Curr. Issues Mol. Biol. 2024, 46(10), 11613-11629; https://doi.org/10.3390/cimb46100689 - 17 Oct 2024

Cited by 8 | Viewed by 18121

Abstract

Hypermobile Ehlers-Danlos syndrome (hEDS) is a connective tissue disorder marked by joint hypermobility, skin hyperextensibility, and tissue fragility. Recent studies have linked hEDS with mast cell activation syndrome (MCAS), suggesting a genetic interplay affecting immune regulation and infection susceptibility. This study aims to decode the genetic basis of mast cell hypersensitivity and increased infection risk in hEDS by identifying specific genetic variants associated with these conditions. We conducted whole-genome sequencing (WGS) on 18 hEDS participants and 7 first-degree relatives as controls, focusing on identifying genetic variants associated with mast cell dysregulation. Participants underwent clinical assessments to document hEDS symptoms and mast cell hypersensitivity, with particular attention to past infections and antihistamine response. Our analysis identified specific genetic variants in MT-CYB, HTT, MUC3A, HLA-B and HLA-DRB1, which are implicated in hEDS and MCAS. Protein–protein interaction (PPI) network analysis revealed significant interactions among identified variants, highlighting their involvement in pathways related to antigen processing, mucosal protection, and collagen synthesis. Notably, 61.1% of the hEDS cohort reported recurrent infections compared to 28.5% in controls, and 72.2% had documented mast cell hypersensitivity versus 14.2% in controls. These findings provide a plausible explanation for the complex interplay between connective tissue abnormalities and immune dysregulation in hEDS. The identified genetic variants offer insights into potential therapeutic targets for modulating mast cell activity and improving patient outcomes. Future research should validate these findings in larger cohorts and explore the functional implications of these variants to develop effective treatment strategies for hEDS and related mast cell disorders. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies, 2nd Edition)

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13 pages, 1651 KB

Open AccessArticle

Impact of Dupilumab on Skin Surface Lipid-RNA Profile in Severe Asthmatic Patients

by Yoshihiko Sato, Hitoshi Sasano, Sumiko Abe, Yuuki Sandhu, Shoko Ueda, Sonoko Harada, Yuki Tanabe, Kyoko Shima, Tetsuya Kuwano, Yuya Uehara, Takayoshi Inoue, Ko Okumura, Kazuhisa Takahashi and Norihiro Harada

Curr. Issues Mol. Biol. 2024, 46(10), 11425-11437; https://doi.org/10.3390/cimb46100680 - 15 Oct 2024

Viewed by 2531

Abstract

The analysis of skin surface lipid-RNAs (SSL-RNAs) provides a non-invasive method for understanding the molecular pathology of atopic dermatitis (AD), but its relevance to asthma remains uncertain. Although dupilumab, a biologic drug approved for both asthma and AD, has shown efficacy in improving symptoms for both conditions, its impact on SSL-RNAs is unclear. This study aimed to investigate the impact of dupilumab treatment on SSL-RNA profiles in patients with severe asthma. An SSL-RNA analysis was performed before and after administering dupilumab to asthma patients requiring this intervention. Skin samples were collected non-invasively from patients before and after one year of dupilumab treatment. Although 26 patients were enrolled, an SSL-RNA analysis was feasible in only 7 due to collection challenges. After dupilumab treatment, improvements were observed in asthma symptoms, exacerbation rates, and lung function parameters. Serum levels of total IgE and periostin decreased. The SSL-RNA analysis revealed the differential expression of 218 genes, indicating significant down-regulation of immune responses, particularly those associated with type 2 inflammation, suggesting potential improvement in epithelial barrier function. Dupilumab treatment may not only impact type 2 inflammation but also facilitate the normalization of the skin. Further studies are necessary to fully explore the potential of SSL-RNA analysis as a non-invasive biomarker for evaluating treatment response in asthma. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies, 2nd Edition)

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Review

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29 pages, 3045 KB

Open AccessReview

Plasmablasts as Translational Biomarkers in Autoimmune Diseases: From Cellular Dynamics to Clinical Decision-Making

by Muhammad Soyfoo and Julie Sarrand

Curr. Issues Mol. Biol. 2026, 48(1), 77; https://doi.org/10.3390/cimb48010077 - 12 Jan 2026

Viewed by 1402

Abstract

B cells are key drivers of immune dysregulation across systemic autoimmune diseases. Among their progeny, plasmablasts occupy a uniquely revealing niche: short-lived, highly proliferative intermediates that mirror real-time B-cell activation. Their appearance in peripheral blood integrates antigenic stimulation, cytokine-driven differentiation, and aberrant germinal-center dynamics, transforming them into sensitive indicators of ongoing immunological activity. This review synthesizes current knowledge on plasmablast biology and highlights disease-specific phenotypes across systemic lupus erythematosus (SLE), primary Sjögren disease (pSjD), IgG4-related disease (IgG4-RD), ANCA-associated vasculitis (AAV), and rheumatoid arthritis (RA). We incorporate molecular insights from single-cell technologies that have uncovered previously unrecognized plasmablast subsets, metabolic states, and interferon-related signatures with prognostic and mechanistic value. Beyond descriptive immunology, plasmablasts are emerging as dynamic biomarkers capable of informing real-time clinical decisions. One of the most robustly supported applications is the prognostic interpretation of plasmablast kinetics following B-cell-depleting therapies, where early reconstitution patterns consistently predict relapse across multiple autoimmune conditions. As clinical immunology shifts from static serological markers toward kinetic, cell-based monitoring, plasmablast quantification offers a path toward precision immune surveillance. Integrating plasmablast dynamics into routine care may ultimately allow clinicians to anticipate disease flares, time therapeutic reinforcements, and transition from reactive management to preventive intervention. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies, 2nd Edition)

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19 pages, 680 KB

Open AccessReview

Ozone as an Immunomodulator—New Therapeutic Possibilities in the Treatment of Immunodeficiencies—A Narrative Review

by Katarzyna Napiórkowska-Baran, Jozef Slawatycki, Paula Klemenska, Paweł Treichel, Ardem Najarian, Gary Andrew Margossian, Maciej Szota, Maria Plocka-Karpinska and Michał Kułakowski

Curr. Issues Mol. Biol. 2025, 47(12), 1016; https://doi.org/10.3390/cimb47121016 - 5 Dec 2025

Cited by 1 | Viewed by 2851

Abstract

Research Subject: Primary and secondary immunodeficiencies represent a growing clinical and public health challenge due to increased susceptibility to infections, impaired immune regulation, chronic inflammation, and disturbances in redox homeostasis. The pathophysiology of these disorders involves dysfunction of innate and adaptive immunity, altered cytokine production, oxidative stress, and reduced activity of antioxidant defense mechanisms. In recent years, attention has increasingly focused on the role of oxidative imbalance and chronic inflammation in weakening immune function. Ozone therapy, when used at controlled low doses, induces a hormetic response that triggers adaptive antioxidant pathways, modulates cytokine profiles, and enhances the activity of immune cells. Due to these properties, ozone has emerged as a potential adjunctive therapy aimed at restoring immune homeostasis and improving clinical outcomes in patients with immune disorders. Aim of Study: The aim of this review is to discuss the role of oxidative stress and immune dysregulation in the pathogenesis of immunodeficiencies and to provide an updated overview of current evidence regarding the therapeutic potential of ozone therapy. This article summarizes molecular mechanisms, biochemical effects, and clinical findings related to ozone-based interventions, with particular emphasis on cytokine modulation, redox balance, macrophage function, regulatory T cells (Treg), and NK cell activity. Materials and Methods: This review is based on scientific data retrieved from PubMed, Scopus, and Google Scholar. Included sources comprise randomized clinical trials, observational studies, meta-analyses, mechanistic studies, and review articles published between 1996 and 2025. Keywords used during the literature search included: “ozone therapy”, “immunomodulation”, “oxidative stress”, “inborn errors of immunity”, “secondary immunodeficiency”, “Treg cells”, “redox homeostasis”. Results: Analysis of current studies shows that controlled low-dose ozone (typically 10–40 µg/mL) activates the Nrf2/ARE antioxidant pathway, increases enzymatic defense (SOD, catalase, GPx), and reduces levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. Clinical trials report improved lymphocyte profiles, enhanced macrophage phagocytic function, increased Treg activity, and reinforced NK cell responses. Patients receiving ozone therapy demonstrate reductions in inflammatory markers (CRP, IL-6, D-dimer), improved redox balance, decreased infection frequency, and better overall immune performance. The therapy is generally well tolerated when administered within established safety guidelines. Conclusions: Available evidence indicates that ozone therapy may serve as a valuable adjunct in the management of immunodeficiencies by modulating immune responses, reducing oxidative stress, and restoring homeostatic balance. Although current clinical outcomes are promising, further multicenter randomized trials are needed to standardize dosing protocols, assess long-term effectiveness, and confirm safety. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies, 2nd Edition)

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23 pages, 1140 KB

Open AccessReview

Hypersensitivity to Folic Acid and/or Folinic Acid—A Review of Clinical Cases, Potential Mechanism, Possible Cross-Allergies and Current Diagnostic Options

by Kinga Lis

Curr. Issues Mol. Biol. 2025, 47(8), 654; https://doi.org/10.3390/cimb47080654 - 14 Aug 2025

Cited by 2 | Viewed by 5786

Abstract

Folic acid and its derivatives (e.g., folinic acid) are a group of water-soluble compounds collectively known as vitamin B9. Synthetic folic acid is a component of dietary supplements, medications and other pharmaceuticals and fortified foods. Folinic acid (5-formyltetrahydrofolic acid) is the active metabolite of folic acid. It is used to treat vitamin B9 deficiency and as an adjunct to various combination therapies. Hypersensitivity reactions to folic acid or folinic acid are rare and occur following exposure to synthetic folic acid or its derivatives but not on natural folates. In people allergic to folates, cross-reactions are possible following exposure to folic acid analogues (including antifolates, e.g., methotrexate). The mechanism of hypersensitivity to folic acid and/or folinic acid has not been clearly established. Both IgE-dependent and non-IgE-dependent hypersensitivity reactions are likely. It is possible that folic or folinic acid is either an immunogen or a hapten. Diagnosing hypersensitivity to folic/folinic acid is difficult. There are no validated in vitro or in vivo diagnostic tests. The basophil activation test (BAT) appears to be a promising tool for diagnosing folate allergy. The aims of the manuscript were to review published clinical cases of hypersensitivity reactions to folic or folinic acid, potential mechanisms of these reactions and possible cross-allergies, and current diagnostic possibilities of folate hypersensitivity. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies, 2nd Edition)

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