Genes and immunity最新文献

Association of gut microbiota composition and microbe–host interactions with response to chemoimmunotherapy in gastric cancer 肠道菌群组成和微生物-宿主相互作用与胃癌化疗免疫治疗反应的关系。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-09-29 DOI: 10.1038/s41435-026-00413-2

Wei Gao, Xinli Wang, Yi Shi, Guangfeng Wu, Min Zhou, Xiaoyan Lin

{"title":"Association of gut microbiota composition and microbe–host interactions with response to chemoimmunotherapy in gastric cancer","authors":"Wei Gao, Xinli Wang, Yi Shi, Guangfeng Wu, Min Zhou, Xiaoyan Lin","doi":"10.1038/s41435-026-00413-2","DOIUrl":"10.1038/s41435-026-00413-2","url":null,"abstract":"Immune checkpoint inhibitors combined with chemotherapy have improved outcomes for advanced gastric cancer, yet only a subset of patients derive benefit, and the contribution of the gut microbiome remains incompletely defined. To identify microbial signatures associated with chemoimmunotherapy response, we performed 16S rRNA gene sequencing on 90 fecal samples collected from 30 patients at baseline, one month after treatment initiation, and at the end of therapy. Patients were stratified by RECIST1.1 criteria into partial response (PR), stable disease (SD), and progressive disease (PD). While overall microbial composition and alpha diversity remained stable over time, immunotherapy enriched Lachnospiraceae and Bacteroidaceae. Notably, baseline microbiota differed significantly among response groups: Senegalimassilia and Lactobacillus were overrepresented in PR patients, whereas Parvimonas, Intestinibacter, and Catenibacterium characterized the SD and PD groups. By integrating public databases, we constructed microbe–metabolite–target and microbe–host interaction networks, indicating that response-associated genera may modulate host genes such as IFNG, IL12B, CXCL6, and DUOX2, thereby influencing CD8+ T cell infiltration. These findings identify gut microbial signatures as predictive biomarkers and provide mechanistic insight into microbiome-mediated chemoimmunotherapy efficacy in gastric cancer.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 5","pages":"572-581"},"PeriodicalIF":4.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PRSS1 isoforms promote type 2 immune responses in IgG4-related disease PRSS1亚型在igg4相关疾病中促进2型免疫反应。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-09-12 DOI: 10.1038/s41435-026-00412-3

Feng Gao, Li Fang, Yuting Zhuang, Jingjie Liu, Lizhen Lin, Hanyi Chen, Juan Tang, Qicai Liu

引用次数: 0

Large-scale GWAS meta-analysis of serum antibody levels in healthy individuals reveals distinct genetic architectures 健康个体血清抗体水平的大规模GWAS荟萃分析揭示了不同的遗传结构。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-08-26 DOI: 10.1038/s41435-026-00408-z

Thomas W. Willis, Effrossyni Gkrania-Klotsas, Nicholas J. Wareham, Eoin F. McKinney, Paul A. Lyons, Kenneth G. C. Smith, Chris Wallace

{"title":"Large-scale GWAS meta-analysis of serum antibody levels in healthy individuals reveals distinct genetic architectures","authors":"Thomas W. Willis, Effrossyni Gkrania-Klotsas, Nicholas J. Wareham, Eoin F. McKinney, Paul A. Lyons, Kenneth G. C. Smith, Chris Wallace","doi":"10.1038/s41435-026-00408-z","DOIUrl":"10.1038/s41435-026-00408-z","url":null,"abstract":"Antibodies are the principal effector proteins of humoral immunity. Dysregulated antibody production is a feature of a number of heritable immune-mediated diseases, such as the antibody deficiencies and IgA nephropathy. To characterize the common-variant architecture of serum antibody levels in the general population, we conducted the largest GWAS meta-analyses to date of serum IgA, IgM and IgG, attaining sample sizes of 85,204, 55,368 and 58,777, respectively. We identified 82 novel associations across three isotypes, including 38 novel IgA associations (of a total of 77), 36 novel IgM associations (of a total of 82) and 8 novel IgG associations (of a total of 14). We found that isotype-specific genetic architecture was largely disjoint, with few signals colocalising across isotypes in spite of their overall positive genetic correlation. We identified a large number of colocalisations between antibody phenotypes and immune-mediated diseases and 16 between antibody phenotypes and a lymphocyte count phenotype. We report a greatly expanded catalogue of serum antibody-associated variants and characterise these in terms of their pathway context and relation to immune pathology.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 5","pages":"553-565"},"PeriodicalIF":4.2,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41435-026-00408-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Compartment-specific regulation of stromal differentiation of the spleen in health and disease 健康和疾病中脾间质分化的室特异性调控。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-08-25 DOI: 10.1038/s41435-026-00411-4

Chayeen Brotzki da Costa, Angéla Kecskés, Tibor Jánosi, Kata Váradi, Zoltán Kellermayer, Péter Balogh

{"title":"Compartment-specific regulation of stromal differentiation of the spleen in health and disease","authors":"Chayeen Brotzki da Costa, Angéla Kecskés, Tibor Jánosi, Kata Váradi, Zoltán Kellermayer, Péter Balogh","doi":"10.1038/s41435-026-00411-4","DOIUrl":"10.1038/s41435-026-00411-4","url":null,"abstract":"Peripheral lymphoid organs in mammals are highly organized, complex tissues that support adaptive immune responses. In terms of comparative developmental biology, the mobile leukocytes of shared hematopoietic lineages in the spleen, lymph nodes, and mucosal lymphoid tissues perform similar functions during antigen recognition and intercellular communication, indicating them as largely homologous. However, the sessile stromal elements within these tissues that create preferential lodging domains for leukocytes differ considerably in their developmental features and structural organization, appearing analogous rather than homologous. Recent studies of splenic stromal architecture have identified region-specific transcription factors, chemokine signatures, and cell surface molecules that guide the specialization of the red pulp and marginal zone, two compartments unique to the spleen. This review—with particular emphasis on Nkx family members as key morphogens regulating spleen development and function—summarizes the roles of critical transcription factors in stromal differentiation pathways, architectural features, and immunological processes under both physiological and pathological conditions.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 5","pages":"495-505"},"PeriodicalIF":4.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41435-026-00411-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SERPINH1 derived from cancer-associated fibroblasts promotes epithelial-mesenchymal transition in clear cell renal cell carcinoma 来自癌症相关成纤维细胞的SERPINH1促进透明细胞肾细胞癌的上皮-间质转化。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-08-24 DOI: 10.1038/s41435-026-00407-0

Ruiying Luo, Shuang Li, Haohao Wang, Zuyu Zhang, Long Li, Panfeng Shang

{"title":"SERPINH1 derived from cancer-associated fibroblasts promotes epithelial-mesenchymal transition in clear cell renal cell carcinoma","authors":"Ruiying Luo, Shuang Li, Haohao Wang, Zuyu Zhang, Long Li, Panfeng Shang","doi":"10.1038/s41435-026-00407-0","DOIUrl":"10.1038/s41435-026-00407-0","url":null,"abstract":"Despite advances in cancer treatment, the prognosis of clear cell renal cell carcinoma (ccRCC) remains poor. The role of CAFs in ccRCC remains unclear. The single-cell sequencing (scRNA-seq) data for ccRCC were downloaded from the GEO database, with the SERPINH1+ fibroblast subpopulation identified. Cancer-associated fibroblasts (CAFs) were determined. In vitro assays analyzed SERPINH1 expression and its impact on ccRCC tumor progression. In vivo animal experiments validated SERPINH1 function. The scRNA-seq data analysis demonstrated that ccRCC cells showed remarkable intratumoral heterogeneity. CAFs were an important source of SERPINH1 in ccRCC, which was further verified in CAFs isolated from tumor tissue. In cell experiments, SERPINH1 from CAFs promoted the up-regulation of TGF-β to induce EMT in ccRCC cells, and TGF-β from tumor cells reinforced the secretion of SERPINH1 from CAFs to form a feedback loop. In vivo experiments elucidated the effects of blocking SERPINH1 function on ccRCC malignant progression. CAFs, as the communication center of TME in ccRCC, secrete SERPINH1 to elevate TGF-β level in tumor cells, and influence epithelial-mesenchymal transition (EMT) and malignant progression of ccRCC. The research helps to elucidate the tumor-promoting mechanism of CAFs and provides a new therapeutic strategy for repressing CAF activation.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 5","pages":"543-552"},"PeriodicalIF":4.2,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and functional consequences of IL33 and IL1RL1 coding variants on IL-33/ST2 signaling IL33和IL1RL1编码变体对IL-33/ST2信号传导的结构和功能影响。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-08-04 DOI: 10.1038/s41435-026-00410-5

Lucie Gelon, Stéphane Roga, Virginie Nahoum, Marlène Pasquet, Naïs Prade, Stéphanie Dufrechou, Laetitia Largeaud, Eric Delabesse, Sophie Voisin, Jean-Philippe Girard, Lionel Mourey, Emma Lefrançais

{"title":"Structural and functional consequences of IL33 and IL1RL1 coding variants on IL-33/ST2 signaling","authors":"Lucie Gelon, Stéphane Roga, Virginie Nahoum, Marlène Pasquet, Naïs Prade, Stéphanie Dufrechou, Laetitia Largeaud, Eric Delabesse, Sophie Voisin, Jean-Philippe Girard, Lionel Mourey, Emma Lefrançais","doi":"10.1038/s41435-026-00410-5","DOIUrl":"10.1038/s41435-026-00410-5","url":null,"abstract":"Interleukin-33 (IL-33) is a central regulator of immune responses and inflammation, and genetic variation in IL33 and its receptor IL1RL1 (ST2) is strongly linked to disease susceptibility, notably asthma. Emerging evidence suggests that IL-33 also influences hematopoietic processes and platelet biology, indicating functions beyond canonical immunity. We investigated two missense variants identified in a patient with unexplained thrombocytopenia: a rare novel IL33 variant, c.385T>C (p.Tyr129His) and the common IL1RL1 variant c.1501_1502CA>AG (p.Gln501Arg), previously associated with reduced IL-33 signaling. Structural modeling revealed that IL-33 Y129H disrupts a conserved hydrogen bond within the IL-33/ST2/IL-1RAcP ternary complex, destabilizing receptor engagement. Functional assays confirmed markedly reduced binding affinity and biological activity, establishing Y129H as a loss-of-function variant. The IL1RL1 Q501R variant affects the Toll/IL-1 receptor (TIR) domain, critical for recruiting adapter proteins such as MyD88. Modeling revealed pronounced perturbation in a peripheral helix of the TIR domain, potentially impacting adapter recruitment and downstream signaling, providing a mechanistic basis for its protective association with asthma. Together, these findings provide structural and functional insights into clinically relevant IL33 and IL1RL1 variants. Their simultaneous occurrence in a patient with thrombocytopenia further supports a potential role for this pathway in platelet homeostasis and stress-responsive hematopoiesis.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 5","pages":"530-542"},"PeriodicalIF":4.2,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A transcriptional signature of resting mast cells is associated with improved disease outcome in HR+HER2- breast cancer 静止肥大细胞的转录特征与HR+HER2-乳腺癌疾病预后的改善有关。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-07-31 DOI: 10.1038/s41435-026-00409-y

Alexander Kirchmair, Claudia Galassi, Esmeralda García-Torralba, Zlatko Trajanoski, Aitziber Buqué, Lorenzo Galluzzi

{"title":"A transcriptional signature of resting mast cells is associated with improved disease outcome in HR+HER2- breast cancer","authors":"Alexander Kirchmair, Claudia Galassi, Esmeralda García-Torralba, Zlatko Trajanoski, Aitziber Buqué, Lorenzo Galluzzi","doi":"10.1038/s41435-026-00409-y","DOIUrl":"10.1038/s41435-026-00409-y","url":null,"abstract":"Breast cancer is the most common malignancy among women worldwide, causing >650,000 deaths annually. Despite advances in personalized therapies, many patients fail to obtain durable benefits from treatments tailored to their disease subtype. For instance, only some patients with PD-L1⁺ triple-negative breast cancer (TNBC) respond to chemotherapy plus immune checkpoint inhibitors. Moreover, while tumor-infiltrating lymphocyte levels correlate with improved survival in TNBC and HER2⁺ breast cancer, this is not true for HR⁺HER2- disease. Thus, other immunobiological features of the breast cancer microenvironment may hold clinically relevant prognostic or predictive value, especially in HR+HER2- tumors. Here, we investigated transcriptional signatures of immune cell infiltration across three public transcriptomic datasets from patients with breast cancer. The relative abundance and activation status of tumor-infiltrating mast cells were consistently associated with shifts in survival indicators amongst patients with HR+HER2- breast cancer. Specifically, infiltration by resting (but not activated) mast cells was associated with prolonged survival, correlating inversely with tumor infiltration by immune cells and proliferation markers in cancer cells, but positively with stromal richness. While based on retrospective transcriptional analyses, these findings suggest that interactions between mast cells and non-malignant components of the breast cancer microenvironment, particularly fibroblasts, may shape disease progression and treatment sensitivity.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 5","pages":"516-529"},"PeriodicalIF":4.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The tumoural landscape of lymphocytes and immune pathways in immunotherapy-treated melanoma patients 免疫疗法治疗的黑色素瘤患者淋巴细胞和免疫通路的肿瘤景观。

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-07-15 DOI: 10.1038/s41435-026-00406-1

Vinícius Gonçalves de Souza, Bruna Pereira Sorroche, Renan de Jesus Teixeira, Hendrigo Nunes, Ana Carolina Laus, Vinícius de Lima Vazquez, Daniele Moraes Losada, Lidia Maria Rebolho Batista Arantes

{"title":"The tumoural landscape of lymphocytes and immune pathways in immunotherapy-treated melanoma patients","authors":"Vinícius Gonçalves de Souza, Bruna Pereira Sorroche, Renan de Jesus Teixeira, Hendrigo Nunes, Ana Carolina Laus, Vinícius de Lima Vazquez, Daniele Moraes Losada, Lidia Maria Rebolho Batista Arantes","doi":"10.1038/s41435-026-00406-1","DOIUrl":"10.1038/s41435-026-00406-1","url":null,"abstract":"Tumor-infiltrating lymphocytes (TILs) shape melanoma behavior and response to immunotherapy, but the links between immune regulation, TIL patterning, and outcomes remain unclear. We retrospectively studied 32 primary melanoma samples from patients treated with anti–PD-1 therapy. Histopathologic TILs were classified as brisk or non-brisk, and primary tumors underwent targeted immune transcriptomic profiling (NanoString nCounter Human Immunology panel). External validation was performed with 96 TCGA-SKCM primary tumors. Brisk tumors displayed broad upregulation of immune transcripts, with enrichment of adhesion pathways (directed global significance scores – DGSS = 2.15) and MHC class II antigen presentation (DGSS = 2.128). Cross-cohort comparison identified 22 shared differentially expressed genes, with ZAP70 remaining significant in both datasets. Brisk tumors also showed higher total TIL (p = 0.036), cytotoxic-cell (p = 0.0095), and Th1 (p = 0.027) scores. Response-associated genes differed by TIL pattern, and subgroup-specific gene scores predicted anti–PD-1 benefit in brisk (4-gene, Area under curve - AUC = 1.000) and non-brisk (3-gene, AUC = 0.852) tumors; the non-brisk score remained independently associated with response (p = 0.029). Higher scores were also associated with prolonged survival. Integrating histopathological TIL patterning with immune transcriptomics may refine prognostication and support immunotherapy stratification in melanoma.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 5","pages":"506-515"},"PeriodicalIF":4.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41435-026-00406-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential role of Akkermansia massiliensis in multiple sclerosis protection by the FcRL3 gene 马氏阿克曼氏菌在FcRL3基因保护多发性硬化中的潜在作用

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-07-11 DOI: 10.1038/s41435-026-00404-3

Valeria Orrù, Michele Marongiu, Eleonora Cocco, Magdalena Zoledziewska

{"title":"Potential role of Akkermansia massiliensis in multiple sclerosis protection by the FcRL3 gene","authors":"Valeria Orrù, Michele Marongiu, Eleonora Cocco, Magdalena Zoledziewska","doi":"10.1038/s41435-026-00404-3","DOIUrl":"10.1038/s41435-026-00404-3","url":null,"abstract":"The contribution of human genetics in shaping the abundance of gut microbiota is small, about 5%; however, it can inform about disease etiopathogenesis, including multiple sclerosis (MS). Searching for MS-gut microbiota cross-comparison of reported genome-wide association studies (GWAS), we identified a coincident association of the disease with a commensal - Akkermansia massiliensis—in the selective Fc receptor of secretory IgA gene (FcRL3). Those two signals colocalized, supporting that lower abundance of A.massiliensis may contribute to MS predisposition. In cis, the FcRL3-MS predisposing signal downregulates the FcRL3 protein production and modulates the dynamic intron usage between naïve and mature B-cells, which we believe to be the primary molecular mechanism associated with MS risk in this region. The signal also increases the expression of the FcRL5 gene. In trans, it reduces the expression of neuropeptide B/W receptor 1 (NPBWR1) and azurocidin (AZU1), whereas it increases the expression of the tumor necrosis factor receptor superfamily, member 13B (TACI). Our view of MS etiopathogenesis suggests that low levels of FcRL3 and A. massiliensis may predispose to MS by causing impaired self-tolerance to commensal microbiota, dysregulation of B-cell function, and immune system effects on the neuroendocrine signaling by AZU1 and NPBWR1 proteins, which may be further investigated as targets for MS.","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":"27 4","pages":"487-493"},"PeriodicalIF":4.2,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic regulation of platelet-derived BDNF by rs11030119: discrepancy between circulating levels and hemostatic function. rs11030119对血小板源性BDNF的遗传调控：循环水平与止血功能之间的差异

IF 4.2 3区医学

Genes and immunity Pub Date : 2026-06-24 DOI: 10.1038/s41435-026-00405-2

Imane Boukhatem, Jessica Blais, Melanie Welman, Jean-Claude Tardif, Marie-Pierre Dubé, Geroges Jourdi, Marie Lordkipanidzé

{"title":"Genetic regulation of platelet-derived BDNF by rs11030119: discrepancy between circulating levels and hemostatic function.","authors":"Imane Boukhatem, Jessica Blais, Melanie Welman, Jean-Claude Tardif, Marie-Pierre Dubé, Geroges Jourdi, Marie Lordkipanidzé","doi":"10.1038/s41435-026-00405-2","DOIUrl":"https://doi.org/10.1038/s41435-026-00405-2","url":null,"abstract":"<p><p>Brain-Derived Neurotrophic Factor (BDNF), highly enriched in platelets, contributes to vascular integrity and thrombotic responses. The rs11030119 variant, located in a BDNF intronic enhancer, has been linked to stroke recovery, but its influence on peripheral BDNF dynamics and hemostasis remains unexplored. In this study, we aimed to understand the impact of rs11030119 on circulating levels of BDNF, and its subsequent effects on thrombus formation. Twenty-six healthy individuals homozygous for either the GG or AA genotype of rs11030119 were matched for age and sex. BDNF and proBDNF levels were quantified in serum, plasma, and platelets. Platelet aggregation, ATP secretion, thrombin generation, and clot firmness were assessed. Washed platelets were also tested with recombinant BDNF. AA carriers displayed significantly lower plasma and serum BDNF levels and diminished BDNF release upon activation, despite comparable platelet BDNF content. The expression of its receptor, TrkB, on the platelet surface was also reduced in AA carriers. However, platelet reactivity, thrombin generation, and viscoelastic clot properties were preserved across genotypes. In conclusion, rs11030119 modulates circulating and platelet-releasable BDNF without impairing hemostatic function, suggesting that BDNF bioavailability may not directly correlate with thrombotic potential. These findings uncover a novel genetic mechanism controlling platelet-derived neurotrophin output.</p>","PeriodicalId":12691,"journal":{"name":"Genes and immunity","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0