Iranian Journal of Allergy, Asthma and Immunology

The Experimental Autoimmune Encephalomyelitis (EAE) Model: A Gateway to Successful Translation of Multiple Sclerosis Therapies

Mansur Aliyu — 2025-09-26

Multiple sclerosis (MS) is a neuroinflammatory disorder that is characterized by demyelination, neurodegeneration, and immune dysregulation. The experimental autoimmune encephalomyelitis (EAE) model has helped to elucidate MS pathophysiology and test therapies. This review synthesizes current literature on the development, applications, and translational significance of EAE models in MS research. It discusses various EAE induction protocols, including active and passive immunization, and highlights advancements such as humanized mice and induced pluripotent stem cell (iPSC)-derived neuronal models. The review evaluates the role of EAE in identifying immune pathways, validating therapeutic agents like glatiramer acetate and natalizumab, and exploring precision medicine approaches through biomarker discovery. The EAE model replicated the key features of MS, including inflammation, demyelination, and axonal loss, facilitating therapy development. However, its predictive validity faces limitations, such as heterogeneity in disease induction, underrepresentation of chronic progression, and species differences. Innovations, such as humanized mouse models and iPSC-derived neurons, show promise in addressing these challenges. EAE research has advanced biomarker-based personalized treatments, although further validation is required. Despite its widespread use, EAE has limitations in terms of variability in disease induction, incomplete MS feature replication, species-specific responses, and clinical translation. Addressing these limitations remains crucial for therapeutic development, focusing on analyzing model limitations and strategies to overcome translational barriers. This review offers immunologists a comprehensive overview of EAE's contributions of EAE to MS research and its potential to inform the development of novel therapeutic approaches for this debilitating disease.

Follistatin-like Protein 3 in Colorectal Cancer: Linking Immune Evasion to Treatment Resistance

Xiangrong Luo — 2025-09-26

Colorectal cancer (CRC) remains a significant global health challenge, characterized by high morbidity and mortality. Despite advances in surgical techniques, chemotherapy, targeted therapies, and immunotherapy, many CRC cases exhibit treatment resistance and immune evasion, necessitating the identification of novel therapeutic targets. Follistatin-like protein 3 (FSTL3) has recently emerged as a key regulator in CRC progression, influencing immune suppression and therapy resistance. FSTL3 modulates the tumor microenvironment by promoting epithelial-mesenchymal transition (EMT), sustaining β-catenin signaling, and stabilizing c-Myc, which collectively enhance tumor invasiveness and metastatic potential. Additionally, FSTL3 contributes to immune evasion by upregulating immune checkpoint molecules such as programmed death-ligand 1 (PD-L1) and indoleamine-2,3-dioxygenase 1 (IDO1), thereby suppressing cytotoxic T-cell activity. High FSTL3 expression correlates with poor prognosis and resistance to conventional chemotherapy, targeted agents, and immune checkpoint inhibitors. Given its pivotal role in CRC pathophysiology, FSTL3 represents a promising biomarker for disease prognosis and a potential therapeutic target. Future research should focus on developing FSTL3-targeted interventions, including monoclonal antibodies, small-molecule inhibitors, and combination strategies with immunotherapy. Understanding the precise molecular mechanisms underlying FSTL3-mediated tumor progression and immune escape will be essential for translating these insights into clinical applications.

Asthma, Atopic Dermatitis, and Allergic Rhinitis in Pediatric Celiac Disease: A Case-control Study

Manijeh Khalili — 2025-09-26

Celiac disease is a gluten-induced immune-mediated enteropathy. Recent studies suggest an increasing association between celiac disease and atopic conditions such as asthma, atopic dermatitis, and allergic rhinitis, although the underlying mechanisms are not fully understood.

In this matched case-control study, the prevalence of asthma, atopic dermatitis, and allergic rhinitis was evaluated among 173 children with celiac disease and 173 age- and sex-matched healthy controls in Zahedan, Iran, in 2023. The diagnosis of celiac disease was based on European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines. Allergic conditions were assessed using the International Study of Asthma and Allergies in Childhood questionnaire and confirmed through clinical evaluation.

Children with celiac disease had a significantly higher prevalence of asthma (12.1% versus 5.8%; odds ratio, 2.25; 95% confidence interval, 1.15 to 4.05) and allergic rhinitis (29.5% versus 14.5%; odds ratio, 2.47; 95% confidence interval, 1.4 to 4.26) compared to controls. There was no significant difference in the prevalence of atopic dermatitis between the two groups (12.1% versus 9.2%; odds ratio, 1.35).

These results indicate that children with celiac disease are at increased risk for certain respiratory allergic diseases, particularly asthma and allergic rhinitis. This highlights the need for integrated care between gastroenterology and allergy specialists. Further research is needed to clarify the shared immunological pathways involved.

A Report on the Clinical Efficacy of Rituximab Administration in Patients with Inborn Errors of Immunity and Autoimmune/Autoinflammatory Manifestations

Samin Sharafian — 2025-09-26

It can sometimes be very difficult to control the manifestations of autoimmunity and lymphoproliferation in patients with primary immunodeficiency diseases, and there is no adequate response to first-line treatments. Rituximab (RTX), as a second-line treatment, is efficacious and well-tolerated for the management of these clinical manifestations.

This retrospective study was conducted to analyze the clinical, immunological, and genetic
findings together with the response rate to RTX therapy in subjects with inborn errors of immunity (IEI) and autoimmune or autoinflammatory manifestations. In this study, 23 individuals with IEI and autoimmune or lymphoproliferation manifestations who received RTX between April 2008 and 2021 were evaluated.

Fifteen out of the 23 patients were female. The median age of cases was 12 years. The moderate and severe adverse reactions, including fever, diarrhea, and anaphylaxis shock, were manifested during RTX infusion in 5 patients. In total, 86.9% of patients responded to rituximab (complete response: n=14, partial response: n=6) while three failed to respond. The median response time to RTX treatment was 50 days. All patients were given monthly intravenous immunoglobulin (IVIG) therapy. Pneumonia and candidiasis occurred in one patient a week after receiving the second injection of RTX. Eight patients expired during follow-up.

In conclusion, the response rate of RTX could be improved through administering monthly IVIG for hypogammaglobulinemia treatment following RTX infusion. Early use of rituximab leads to a better response rate in comparison with late use of rituximab in multitreated refractory patients. The efficient cumulative dose of rituximab remains undefined.

Respiratory Health Risks in Hairdressing: A Cross-sectional Study of Occupational Subgroups

Mahsa Choroom Kheirabadi — 2025-09-26

Occupational exposure in hairdressing is associated with significant respiratory health risks, including impaired lung function and respiratory symptoms. This study aimed to evaluate and compare respiratory symptoms and pulmonary function across subgroups of hairdressers categorized by their specific exposure profiles.

A cross-sectional analysis was conducted involving 152 female hairdressers in Tehran, Iran, who were stratified into four subgroups: (1) individuals with direct exposure to hair dyes, dechlorinating agents, and keratinizing substances; (2) individuals exposed to varnish, acetone, and nail implant materials; (3) individuals exposed to adhesives for hair and eyelash extensions; and (4) individuals with minimal or no direct chemical exposure. Respiratory and nasal symptoms were assessed using the European Community Respiratory Health Survey (ECRHS) III questionnaire. spirometry measurements, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, and forced expiratory flow at 25–75% of FVC (FEF25–75), were performed to evaluate pulmonary function.

Overall, 42.1% of participants reported respiratory symptoms, with subgroup 1 exhibiting the highest prevalence. Cough (64.3%), wheezing (35.7%), and dyspnea (64.3%) were the most commonly reported symptoms, while 22.4% reported nasal symptoms. Subgroup 1 demonstrated significantly lower pulmonary function indices and a higher prevalence of obstructive lung patterns (40.5%). Bronchodilator responsiveness indicative of asthma was observed in 34.2% of participants.

In conclusion, direct occupational exposure to hairdressing chemicals, particularly hair dyes and bleaching agents, is associated with substantial respiratory impairment. Implementation of regular health surveillance, personal protective equipment, and enhanced workplace ventilation is strongly recommended

Analysis of the Relationship between Pan-immune-inflammation Value and the Clinical Pathological Characteristics and Surgical Prognosis of Thyroid Cancer

Wei Liang — 2025-09-26

This study aimed to explore the relationship between the preoperative pan-immune-inflammation value (PIV) and the clinicopathological characteristics and surgical prognosis of thyroid cancer.

This retrospective cohort study included 165 patients with thyroid cancer who underwent surgery. The value and clinical applicability of PIV and other immune-inflammatory biomarkers in assessing disease-free survival (DFS) were compared based on the area under the receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA). Patients were divided into high and low PIV groups according to the optimal cutoff value to assess the correlation between PIV and pathological characteristics. The Kaplan-Meier method was used for DFS analysis, and a Cox proportional hazards model was used to analyze the factors affecting DFS.

The AUC of PIV for predicting DFS was higher than that of other immune-inflammatory biomarkers, and PIV demonstrated the highest clinical utility. Compared with the low PIV group, the high PIV group had a lower proportion of papillary thyroid carcinoma, a higher proportion of anaplastic thyroid carcinoma, and higher rates of stage III–IV disease, lymph node metastasis, maximum tumor diameter ≥2 cm, and multiple lesions. The DFS was significantly shorter in the high PIV group than in the low PIV group. After adjusting for confounding factors, a high PIV level was an independent risk factor for poor surgical outcomes.

In conclusion, preoperative PIV is associated with the pathological type of thyroid cancer, TNM stage, lymph node metastasis status, and maximum tumor diameter. Furthermore, a high PIV level can increase the risk of poor surgical outcomes.

The Relationship between Thioredoxin-2, Systemic Immune-inflammatory Index, and Short-term Adverse Cardiovascular Events in Septic Cardiomyopathy

Yafei Zhang — 2025-09-26

To explore the relationship between thioredoxins (Trx) -2, systemic-immune inflammatory index (SII), and short-term major adverse cardiac events (MACE) in septic cardiomyopathy (SCM).

A retrospective study was conducted on 98 SCM patients admitted to Affiliated Jinling Hospital, Medical School of Nanjing University Emergency Intensive Care Unit (EICU) from July 2022 to June 2024. Patients underwent routine blood tests and data assessment upon admission. Based on the occurrence of MACE by day 28, patients were divided into the MACE group and the non-MACE (N-MACE) group. Clinical data were collected, and logistic regression, along with restricted cubic spline models, analyzed the relationships between SII, Trx-2, and MACE risk in SCM patients.

Among the 98 SCM patients included, there were 35 (35.71%) in the MACE group and 63 (64.29%) in the N-MACE group. Logistic regression analysis showed that elevated SII and serum Trx-2 levels correlated with an increased risk of MACE within 28 days post-admission for SCM patients. Restricted cubic spline analysis revealed a linear dose-response relationship between both SII and Trx-2 levels with short-term MACE risk in SCM. The ROC curve showed AUC values of 0.869 for LVEF, 0.881 for SII, while combining SII + Trx-2 yielded 0.926 (95% CI: 0.862-0.989), with specificity at 83.98% and sensitivity at 98.80%.

The abnormal increase of serum SII and Trx-2 levels in SCM patients is related to the occurrence of MACE within 28 days after admission. The risk of MACE increases with the increase of serum SII and Trx-2 levels.

Association between HLA-DRB1.2 Genotypic Diversity and Cervical Cancer in Women Infected with the Human Papillomavirus

Somaye Sedaghat — 2025-09-26

Cervical cancer is a significant public health concern, particularly in women infected with the human papillomavirus (HPV). Recent evidence suggests that host genetic factors, specifically those related to the human leukocyte antigen (HLA) system, may also play a crucial role in determining susceptibility to cervical cancer in HPV-infected individuals.

In this study, 86 patients with HPV and 27 healthy donors were selected from May 2023 to February 2024. HLA-DRB1 genotypes were determined using polymerase chain reaction followed by high-resolution melting curve analysis (HRM). Genotype frequencies in patients were compared with those in the control group from donors.

Based on the HRM analysis, 10 genotypes were found in both patients and controls (profiles A-J). In the analysis of HLA-DRB1 genotypes, C, F, and I showed significant associations with HPV infection, indicating a possible protective effect against infection. Notably, genotype B was strongly linked to high-risk HPV, while genotype A was associated with low-risk HPV and is relevant to infection history. However, the remaining genotypes examined in the study did not exhibit significant associations with the analyzed parameters.

This study contributes valuable evidence regarding the role of HLA-DRB1 genotypes in cervical cancer susceptibility and highlights the potential clinical implications for risk assessment and targeted immunotherapies. The use of HRM for HLA typing offers advantages that are efficient, accurate, and scalable, making it suitable for large-scale studies and clinical applications.

Exploring the Therapeutic Potential of Fluorinated CXCR4 Inhibitor A1: Insights from Breast Cancer In Vitro Investigations

Ali Rahimi — 2025-09-26

The impacts of the CXC motif chemokine 12 (CXCL12)/ C-X-C chemokine receptor type 4 (CXCR4) axis on the infiltration of anti-tumor and pro-tumor immune cells in the tumor microenvironment (TME) of breast cancer (BCa) have been noted in previous studies. Accordingly, regulating the downstream signals of this axis can effectively increase CD8⁺ cytotoxic T cells and decrease the frequency of immunosuppressive cells in the TME. This study investigated the anti-tumor effects of N, N''-thiocarbonylbis (N'-(3,4-dimethylphenyl)-2,2,2 trifluoroacetimidamide) (A1), a novel fluorinated CXCR4 inhibitor on a BCa cell line.

In this study, the impacts of A1 on cell viability, proliferation, apoptosis, and cell cycle were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. Moreover, the effect of A1 on the number of CXCR4⁺ 4T1 cells was measured by flow cytometry.

A1 treatment exhibited cytotoxic effects on 4T1 cells, promoting cell apoptosis and G₂/M cell cycle arrest. In addition, A1-treated cells showed a reduced cell proliferation than CXCL12 treated cells. Furthermore, treatment with A1 alongside CXCL12 significantly decreased the number of CXCR4⁺ cells compared to the control group treated with only CXCL12 as a proliferator factor.

These results indicate that A1 exerts potential anti-tumor effects and may serve as a possible therapeutic agent for BCa treatment; however, further studies are required.

The Role of LINC02381 in Modulating Cisplatin Resistance in Ovarian Cancer: A Bioinformatics Approach

Zeinab Karbalaei Pazoki — 2025-09-26

Cisplatin resistance presents a significant challenge in cancer therapy, emphasizing the necessity for identifying new regulatory elements that influence drug response. Recent research has revealed the importance of long noncoding RNAs (lncRNAs) in chemotherapy resistance, with LINC02381 identified as a potential regulatory factor.

Through an in-depth bioinformatics analysis, we investigated the impact of LINC02381 on cisplatin resistance in ovarian cancer across various datasets. By conducting differential expression analysis, survival analysis, gene set enrichment analysis (GSEA), and constructing protein-protein interaction (PPI) networks, we identified key pathways associated with LINC02381 expression.

The results indicated that the altered expression of LINC02381 in patients treated with cisplatin was associated with reduced survival. Functional studies and correlation analyses further demonstrated that this LncRNA influences critical pathways and genes related to apoptosis, efflux, DNA repair, and EMT. Lastly, through an examination of its interactions with microRNA and protein networks, we identified LINC02381 as a ceRNA implicated in cisplatin resistance.

Our findings suggest that LINC02381 may influence cisplatin sensitivity in ovarian cancer and establish a basis for further experimental validation, including molecular assays or in vivo analyses, and suggest the potential therapeutic targeting of LINC02381 to combat chemoresistance.

Exploring Inflammatory-Related Hub Genes as Therapeutic Targets in Major Depressive Disorder: Implications for Immunological Pathways

Ruiqi Wang — 2025-09-26

This study explored the mechanisms of action of inflammation related central genes in severe depression (MDD) and analyzes their potential as therapeutic targets. By identifying key genes and establishing the link between immune regulatory mechanisms and depression, we provide a theoretical basis for developing more accurate diagnostic and treatment methods.

Gene expression datasets related to MDD were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) associated with inflammatory processes were identified and analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Additionally, we explored regulatory networks of miRNAs, transcription factors, and potential drug interactions were explored. Immune infiltration analysis was performed to examine immune cell profiles.

Seven key genes—HMGB1, HSP90AB1, MAPK1, MMP9, MYD88, S100A12, and TLR2—were identified as central players in the inflammatory pathways underlying MDD. These genes demonstrated moderate diagnostic accuracy with AUC values ranging from 0.5 to 0.7. Enrichment analyses revealed significant associations with immune signaling pathways, including IL-17 and Toll-like receptor signaling. Immune infiltration analysis highlighted altered abundances of regulatory T cells, neutrophils, and dendritic cells in MDD samples.

Inflammatory-related hub genes play crucial roles in linking immune dysregulation to the pathophysiology MDD pathophysiology. These findings offer insights into the immunological underpinnings of MDD and present potential therapeutic targets for intervention through immune-modulatory approaches.

Elucidating the Molecular Pathways of Long Noncoding RNA C6orf223 in Colorectal Cancer via microRNA Interactions and Transcriptomic Profiling

Sara Tutunchi — 2025-09-26

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with high-risk cases showing increased aggressiveness and poor prognosis. Recent studies suggest that long noncoding RNAs (lncRNAs) such as C6orf223 may play crucial roles in CRC progression. This study investigated the expression and regulatory role of C6orf223 in high-risk versus low-risk CRC patients, focusing on its potential as a biomarker for diagnosis and prognosis.

We conducted differential expression analysis using RNA-seq data to identify key genes in high-risk CRC, followed by correlation and pathway enrichment analyses to understand C6orf223. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves assessed the prognostic and diagnostic potential of C6orf223. RNA methylation and mutation patterns were analyzed to explore post-transcriptional regulation and genetic alterations in high-risk CRC.

C6orf223 was significantly upregulated in high-risk CRC. High C6orf223 expression was associated with poor overall survival, and a biomarker panel that includes C6orf223 and microRNAs showed strong potential for accurate diagnosis. Methylation and mutation analyses revealed potential mechanisms enhancing C6orf223’s stability and oncogenic activity.

Our findings indicate that C6orf223 acts as a binder to and inhibits tumor-suppressive microRNAs, reducing their availability to regulate cancer-promoting genes and may serve as a valuable biomarker for CRC diagnosis and prognosis. Further research on lncRNA-microRNA interactions could provide insights for novel CRC therapies.

Clinical Analysis of Two Cases of Histiocytic Necrotizing Lymphadenitis Complicated with Macrophage Activation Syndrome

Jingjing Jin — 2025-09-26

The Article Abstract is not available.

Immunological Insights into the PI3K-Akt Pathway in Osteoporosis and Periodontitis: A Proteomic and Metabolomic Approach

Jing Qi — 2025-09-26

The Article Abstract is not available.