Immunologic Research最新文献

{"title":"Otorhinolaryngological manifestations of systemic autoimmune and autoinflammatory diseases: a comprehensive review.","authors":"Nuray Bayar Muluk, Cemal Cingi","doi":"10.1007/s12026-026-09861-4","DOIUrl":"https://doi.org/10.1007/s12026-026-09861-4","url":null,"abstract":"<p><p>In many autoimmune and autoinflammatory diseases, the head and neck are the first sites of symptom manifestation. Recognizing these early signs is crucial to prevent diagnostic delays and fatal consequences. This review addresses: (1) specific otorhinolaryngological (ENT) manifestations indicating systemic diseases (2), evidence for differentiating these from isolated ENT disorders, and (3) the multidisciplinary role in patient management. A comprehensive narrative literature review was conducted utilizing established scientific databases, including PubMed/Medline, Scopus, Web of Science, and Embase, covering articles published from 1983 up to 2026. A structured search strategy applied keywords like \"systemic disorders,\" \"ENT symptoms,\" \"granulomatosis with polyangiitis,\" and \"Sjögren syndrome.\" Peer-reviewed clinical trials, mechanistic studies, and authoritative guidelines were included to synthesize current evidence regarding the clinical detection and management of systemic diseases through ENT manifestations. ENT symptoms typically manifest locally before systemic organ involvement. Sensorineural hearing loss (SNHL) frequently accompanies autoinflammatory diseases. Auricular chondritis strongly indicates relapsing polychondritis (RP). Granulomatosis with Polyangiitis (GPA) and RP classically present with refractory rhinosinusitis, nasal crusting, and saddle-nose deformities. Orally, Sjögren syndrome causes severe sicca syndrome, while Behçet's disease leads to mucosal ulcerations. Furthermore, GPA (developing in 2-20% of cases) and RP are common causes of potentially fatal laryngeal involvement, including progressive subglottic stenosis. ENT manifestations frequently herald severe systemic diseases. Early detection by otolaryngologists is vital. Implementing a multidisciplinary strategy that integrates rheumatology and internal medicine ensures timely diagnosis, facilitates appropriate systemic immunosuppression, and significantly improves patient survival and overall quality of life.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"The cost-benefit of newborn screening for X-linked agammaglobulinemia and related B-cell lymphopenia\".","authors":"Ercan Yılmaz, Erdem Topal","doi":"10.1007/s12026-026-09856-1","DOIUrl":"https://doi.org/10.1007/s12026-026-09856-1","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of immune checkpoint-related polymorphisms in PD-1, PD-L1, and CTLA-4 genes with susceptibility to genitourinary cancer: a meta-analysis.","authors":"Chih-Heng Chen, Su-Wei Hu, Chia-Chang Wu, Yuan-Hung Wang","doi":"10.1007/s12026-026-09860-5","DOIUrl":"10.1007/s12026-026-09860-5","url":null,"abstract":"<p><p>This meta-analysis explored the association of immune checkpoint-related single-nucleotide polymorphisms (SNPs) in programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) genes with susceptibility to various genitourinary (GU) cancers, including urothelial carcinoma (UC), renal cell carcinoma (RCC), and prostate cancer (PCa). PubMed, Embase, Cochrane Library, and Web of Science were searched for case-control studies from inception to April 2026. Six SNPs, including PD-1 (rs2227981), PD-L1 (rs4143815), and CTLA-4 (rs3087243, rs231775, rs5742909, and rs11571302), were examined. The relationships between the SNPs and cancer susceptibility were evaluated using pooled odds ratios (ORs) and 95% confidence intervals (CIs) for dominant, recessive, and allele models. This study considered 16 case-control studies. PD-L1 rs4143815 was associated with a significantly decreased risk of UC in Asian populations under the dominant model (CC + CG vs. GG: OR = 0.34, 95% CI = 0.14-0.87). CTLA-4 rs5742909 polymorphism was associated with an increased risk of GU cancer in dominant model (TT + TC vs. CC: OR = 1.41, 95% CI = 1.11-1.80) and allele model (T vs. C: OR = 1.34, 95% CI = 1.05-1.72). A significantly increased risk of UC was further identified among Asian population in the dominant model (OR = 1.56, 95% CI = 1.04-2.34). No significant associations were observed for the other SNPs. In conclusion, specific polymorphisms in immune checkpoint-related genes, particularly PD-L1 rs4143815 and CTLA-4 rs5742909, are associated with susceptibility to GU cancer in Asian populations.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eupatorin interferes with NLRP3 inflammasome activation via modulation of NF-κB signaling pathway in LPS induced macrophages.","authors":"Farheen Mansoor, Almas Jabeen, Atiya Habib, Sidrah Shams, Shabana U Simjee, Samina Bano, Shaheen Faizi, Zaheer Ul-Haq","doi":"10.1007/s12026-026-09857-0","DOIUrl":"10.1007/s12026-026-09857-0","url":null,"abstract":"<p><p>NOD-like cytosolic receptors (NLRs) are crucial in both nonspecific and specific immunity. Among them, the NLRP3 (NOD-like receptor family pyrin domain-containing 3) gains clinical attention, where its hyperactivation causes inflammatory, autoimmune, and metabolic illnesses. We investigated the effects of the flavone eupatorin (3', 5-Dihydroxy 4', 6, 7-trimethoxy flavone) on the NLRP3 inflammasome and associated proteins utilizing in vitro and in silico approaches. Eupatorin modulates the NLRP3 and associated molecules' expression in lipopolysaccharide (LPS)-primed, adenosine 5'-triphosphate (ATP)-stimulated THP-1 cells through downregulation of NF-ĸB phosphorylation, with promising effects as observed with standard tranilast. Additionally, the suppression of zymosan-induced intracellular oxidative stress and LPS-induced nitric oxide (NO) revealed anti-inflammatory effects. The strong binding affinity of -8.276 kcal/mol of the compound with NLRP3 was observed at the ATP binding pocket as shown by the standard tranilast, -7.834 kcal/mol, where interaction with NF-kB also provides comparable results with binding affinities of -3.93 and - 3.17 kcal/mol, respectively. The in silico results support the in vitro findings. Eupatorin appears to be a potential medication option for NLRP3-driven inflammatory and metabolic diseases and deserves further development as an inflammasome inhibitor.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of cellular exhaustion-related genes and CD4 + T cell disturbances in immunological non-responders on antiretroviral therapy.","authors":"Henrique Fernando Lopes-Araujo, Wlisses Henrique Veloso Carvalho-Silva, José Leandro Andrade-Santos, Maria Carolina Santos Guedes, Fabrício Oliveira Souto, Luiz Cláudio Arraes De Alencar, Igor de Farias Domingos, Paulo Sérgio Ramos de Araújo, Kleyverson Feliciano-Santos, Rafael Lima Guimarães","doi":"10.1007/s12026-026-09859-y","DOIUrl":"10.1007/s12026-026-09859-y","url":null,"abstract":"<p><p>Antiretroviral therapy suppresses HIV replication, but 10-40% of people living with HIV do not reconstitute CD4 + T cell counts despite viral suppression. Cellular exhaustion and alteration in the frequency of CD4 + T cell subsets are mechanisms involved in immunological nonresponse. This study investigated cellular exhaustion through gene expression and frequencies of CD4 + T cell subpopulations through flow cytometry in 36 male individuals living with HIV (28 immunological responders and 8 immunological non-responders) after 18 months of treatment. Gene expression analysis revealed significantly upregulation of PDCD1 (fold change = 1.81; p = 0.0003) and TIGIT (fold change = 1.80; p = 0.0055) in immunological non-responders compared to immunological responders, with ROC curve analysis confirming discriminatory ability. Flow cytometry demonstrated lower frequencies of recent thymic emigrant (19.42 ± 7.76 vs. 32.29 ± 10.68; p = 0.0285) and naive CD4 + T cells (26.10 ± 9.41 vs. 47.65 ± 13.45; p = 0.0194) in immunological non-responders compared to immunological responders. Moreover, we observed higher frequency of central memory CD4 + T cells (47.94 ± 13.42 vs. 32.58 ± 9.89; p = 0.0184), with excellent discriminatory capacity. TIGIT expression inversely correlated with recent thymic emigrant (r = -0.7284; p = 0.0013) and naive CD4 + T cells (r = -0.7394; p = 0.0010), and directly with central memory CD4 + T cells (r = 0.7264; p = 0.0014). These findings emphasize cellular exhaustion and dysregulated CD4 + T cell subsets as critical factors of immunological nonresponse.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human endogenous retroviruses antibody signatures in severe asthma phenotypes.","authors":"Milena Fais, Rachele Campus, Elena Rita Simula, Maria Carmina Pau, Barbara Piras, Pietro Pirina, Leonardo A Sechi","doi":"10.1007/s12026-026-09855-2","DOIUrl":"10.1007/s12026-026-09855-2","url":null,"abstract":"<p><p>Human endogenous retroviruses (HERVs) represent approximately 8% of the human genome and have been increasingly implicated in the pathophysiology of immune-related disorders. In this study, we investigated the humoral response against specific antigenic peptides derived from HERV-H, HERV-K, and HERV-W in the plasma of patients across different asthma phenotypes, including non-severe and severe cases, compared to healthy controls (HCs). Our results show that antibody levels against HERV-W were significantly low in the asthmatic population, showing a progressive downregulation that was more pronounced in severe cases. Conversely, a distinct and robust upregulation was uniquely observed for HERV-H in severe asthma cases, reaching a 100% positivity rate. Furthermore, HERV-K antibody levels were significantly lower in the non-severe asthmatic subtype compared to HCs. Interestingly, Spearman analysis revealed significant positive correlations among all tested HERV peptides within the Asthmatic cohort, a co-regulatory trend that became substantially reinforced within the Severe Asthma subgroup. These findings highlight a specific immune dysregulation pattern where a synchronized HERV expression tightly correlates with disease severity and phenotypical classification. The HERV epitopes identified in this exploratory study appear to be key targets of the humoral response in asthmatic patients, suggesting that circulating antibody levels against these retroviral elements could serve as potential tools for exploratory disease stratification and refractory phenotype characterization.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term immunological impairment after early thymectomy in congenital heart disease.","authors":"José Roberto Mendes Pegler, Débora Linhares Rodrigues, Renata de Almeida Bordim, Patricia Palmeira, Andréia Rangel-Santos, Isabela de Jesus Silva Avelar, Ana Cristina Sayuri Tanaka, Estela Azeka, Nana Miura Ikari, Magda Maria Sales Carneiro-Sampaio, Marcelo Biscegli Jatene, Antonio Carlos Pastorino","doi":"10.1007/s12026-026-09858-z","DOIUrl":"10.1007/s12026-026-09858-z","url":null,"abstract":"<p><p>Early thymectomy during congenital heart disease repair may impair thymic output, but long-term effects across age groups remain incompletely defined. We evaluated T-cell receptor excision circles (TRECs) and a comprehensive panel of lymphocyte subsets in 20 adults (mean age, 29.6 years) and 16 children (mean age, 10.7 years) who underwent thymectomy within the first year of life, and in age- and sex-matched controls. TRECs were lower in patients than controls in adults (34 ± 25 vs. 79 ± 45 copies/μL; FDR-adjusted p = 0.001) and children (9 [7-15] vs. 95 [65-160] copies/μL; FDR-adjusted p < 0.0001). Total lymphocyte and T-cell counts were reduced in both age groups, mainly due to lower naïve CD4⁺ and CD8⁺ T cells, including recent thymic emigrants. Most non-naïve subsets did not differ significantly from controls. Regulatory T-cell (Treg) alterations differed by age: children showed broad reductions, whereas adults showed selective naïve Treg reduction. Early thymectomy is associated with persistent thymic output impairment, including in adults approximately three decades after surgery, and with age-specific Treg alterations.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One threshold does not fit all: assay-specific validation of anti-tTG IgA tests for biopsy-free diagnosis of pediatric celiac disease.","authors":"Maria Barrale, Maria Fregapane, Vincenzo Cantisano, Valeria Motisi, Danilo Villalta, Nicola Bizzaro, Ignazio Brusca","doi":"10.1007/s12026-026-09852-5","DOIUrl":"10.1007/s12026-026-09852-5","url":null,"abstract":"<p><strong>Background: </strong>The ESPGHAN biopsy-free diagnostic algorithm for pediatric celiac disease (CeD) requires serum IgA anti-tissue transglutaminase antibody (anti-tTG IgA) concentrations ≥10 times the upper limit of normal (ULN) in the first blood sample, together with positive IgA endomysial antibodies (EMA) in a second blood sample. However, the transferability of the 10×ULN anti-tTG IgA threshold across different analytical platforms remains uncertain owing to the lack of assay harmonization.</p><p><strong>Methods: </strong>Eighty-four children (6-10 years) who underwent duodenal biopsy during the diagnostic work-up for suspected CeD were retrospectively evaluated. Histology was classified according to the Marsh-Oberhuber criteria (65 Marsh-Oberhuber 3, 12 Marsh-Oberhuber 2, and 7 Marsh-Oberhuber 1). Anti-tTG IgA antibodies were measured using one FEIA assay (EliA Celikey IgA) and two CLIA platforms (QUANTA Flash® and Maglumi®). EMA were assessed by indirect immunofluorescence on distal monkey esophagus. ROC analysis evaluated discrimination of mucosal atrophy (Marsh-Oberhuber 3) from non-atrophic lesions (Marsh-Oberhuber 1-2).</p><p><strong>Results: </strong>Anti-tTG IgA concentrations correlated significantly with histological severity for all assays (Spearman's ρ=0.670-0.736; p<0.0001). AUCs ranged from 0.961 to 0.992. At 10×ULN, QUANTA Flash® showed 100% sensitivity and 47.4% specificity, whereas Maglumi® and EliA Celikey IgA showed 100% specificity with sensitivities of 70.8% and 86.2%, respectively. For QUANTA Flash®, 42×ULN was required to achieve 100% specificity. In analyses targeting PPV ≥95%, the corresponding thresholds were 7.54×ULN for Maglumi®, 28.55×ULN for QUANTA Flash®, and 6.10×ULN for EliA Celikey IgA.</p><p><strong>Conclusions: </strong>In this selected anti-tTG IgA-positive cohort, the quantitative relationship between anti-tTG IgA and mucosal atrophy differed across automated assays. Expression of results as multiples of the ULN did not fully compensate for inter-assay analytical variability. These findings support assay-specific verification of decision limits, but the retrospective design and selection based on QUANTA Flash positivity limit generalization of the diagnostic performance estimates to unselected children undergoing evaluation for CeD.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmenting antitumor immunity in colon cancer via GSDMD-mediated pyroptosis induced by an attenuated Salmonella delivery system.","authors":"Bingran Han, Xu Si, Chuanjie Liu, Ziwei Ai, Jingyuan Zhu, Xurui Chai, Pengkun Wei, Zhiang Liu, Xiaolong Jia, Sheng Guo, Tiesuo Zhao, Huijie Jia","doi":"10.1007/s12026-026-09851-6","DOIUrl":"10.1007/s12026-026-09851-6","url":null,"abstract":"<p><p>As a major gastrointestinal malignancy, colon cancer (CC) demands more effective therapies. Gene therapy is an emerging promising strategy, and pyroptosis, a novel lytic cell death form, serves as a vital antitumor target, with Gasdermin D (GSDMD)-a key pore-forming protein in pyroptosis-showing anti-CC potential. We constructed an engineered attenuated Salmonella strain to deliver a GSDMD-expressing plasmid, and verified its therapeutic efficacy via in vitro and in vivo studies. In CC cell lines, the Salmonella vector upregulated GSDMD and cleaved caspase-1 (its upstream activator), inhibiting cell proliferation and inducing pyroptosis. In CC-bearing mice, the strain significantly suppressed tumor progression, reduced Ki67 expression, elevated intratumoral GSDMD and cleaved caspase-1 levels, and enhanced CD4⁺ and CD8⁺ T cell infiltration to boost antitumor immunity. This study suggests that attenuated Salmonella-mediated GSDMD delivery combats CC by triggering pyroptosis and stimulating antitumor immunity, laying a foundation for GSDMD-targeted gene therapeutics.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D status and supplementation as potential modifiers of allergen immunotherapy outcomes in respiratory allergy: A structured narrative review.","authors":"Selda Ali, Denisa-Mihaela Iordan, Andreea-Iulia Vlădulescu-Trandafir, Roxana Silvia Bumbăcea","doi":"10.1007/s12026-026-09854-3","DOIUrl":"https://doi.org/10.1007/s12026-026-09854-3","url":null,"abstract":"<p><p>Allergen immunotherapy (AIT) represents a cornerstone in managing IgE-mediated allergic diseases, such as allergic rhinitis and asthma. By administering controlled doses of allergens over time, AIT aims to readjust immune tolerance, thereby modifying allergic responses. However, clinical responses to AIT remain heterogeneous, with a subset of patients achieving only partial benefit. This heterogeneity underlines the need for novel adjunctive approaches to potentiate the immunomodulatory effects of AIT. In this context, vitamin D has gained considerable interest, given its well-established role in immune homeostasis and regulation, as well as its emerging relevance in modulating allergic disease. This structured narrative review aims to assess the potential role of vitamin D supplementation during AIT on clinical outcomes as well as the significance of endogenous vitamin D levels on AIT clinical efficacy. A total of 18 studies were reviewed, 13 evaluating the impact of vitamin D supplementation during AIT and 5 assessing the influence of endogenous vitamin D levels on AIT outcomes. Most supplementation studies reported clinical outcomes favoring the addition of vitamin D to AIT, but three found no additional benefit, and two reported a benefit only at an earlier time point, respectively in vitamin D-deficient patients. Of the five studies examining endogenous status, three reported that higher 25-hydroxyvitamin D (25(OH)D) levels were associated with better AIT outcomes. Other findings that were reported as secondary outcomes included favorable immunologic changes, such as IL-10 production, decreased allergen-specific IgE levels, and enhanced regulatory Treg-cell activity, without formal assessment of their contribution to clinical benefit. Nevertheless, findings remain inconsistent across studies due to heterogeneity in study design, supplementation regimens, and outcome measures. While the available evidence suggests that adequate vitamin D status or supplementation may be associated with better clinical responses to AIT, the current findings remain limited by heterogeneity in study design, supplementation regimens, outcome measures, and generally small sample sizes. Therefore, the evidence should be considered suggestive rather than conclusive. Although correction of vitamin D deficiency is appropriate on general clinical grounds, its specific use as an adjunct to improve AIT outcomes cannot yet be routinely recommended. Further adequately powered, standardized, placebo-controlled studies are needed to clarify its role and inform clinical recommendations.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"74 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}