Zerrin Yulugkural, Mustafa Yildiz, Ertugrul Topcu, Habibe Tülin Elmaslar Mert, Alp Temiz
{"title":"Epigenetic Modulation of IL-7 and IL-10: Toward Personalized Immune Therapies in Viral Epidemics.","authors":"Zerrin Yulugkural, Mustafa Yildiz, Ertugrul Topcu, Habibe Tülin Elmaslar Mert, Alp Temiz","doi":"10.1155/jimr/9467657","DOIUrl":"10.1155/jimr/9467657","url":null,"abstract":"<p><strong>Background: </strong>Host immune responses, including cytokine production, shape the severity of viral epidemics. Epigenetic mechanisms such as DNA methylation regulate cytokine gene expression and may contribute to immune dysregulation in severe disease.</p><p><strong>Methods: </strong>This study analyzed interleukin-7 (IL-7), IL-8, and IL-10 promoter methylation in 145 COVID-19 patients (91 wards, 54 intensive care units (ICUs)), excluding 12 patients receiving epigenetically active drugs. Peripheral blood DNA underwent bisulfite conversion, followed by PCR and gel electrophoresis. Gene-specific methylation levels were quantified using beta values.</p><p><strong>Results: </strong>IL-7 was significantly hypermethylated overall (β = 0.835, <i>p</i> < 0.001), especially in ICU patients (β = 0.863, <i>p</i> = 0.001), independent of age, mortality, and malignancy. An interaction between age and ICU status indicated group-specific effects. IL-10 showed significant hypomethylation (β = 0.243, <i>p</i> < 0.001), while IL-8 methylation did not differ significantly (<i>p</i> = 0.373). ICU patients had higher mortality (26% vs 5.5%, <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>IL-7 hypermethylation may impair T-cell-mediated immunity in severe cases, while IL-10 hypomethylation may reflect enhanced immunosuppression. These findings suggest a role for epigenetic cytokine regulation in disease progression and may guide future immunomodulatory strategies.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 ","pages":"9467657"},"PeriodicalIF":3.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12780970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952034","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}
Mojdeh Soltani, Sara Falahi, Mohammad Abbaszadeh, Mark J M Sullman, Hamed Fouladseresht, Nahid Eskandari
{"title":"Neutrophil Plasticity and NETosis in Tumour Microenvironment: Tumour Evolution and Therapy Resistance.","authors":"Mojdeh Soltani, Sara Falahi, Mohammad Abbaszadeh, Mark J M Sullman, Hamed Fouladseresht, Nahid Eskandari","doi":"10.1155/jimr/5568021","DOIUrl":"10.1155/jimr/5568021","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) are web-like formations consisting of DNA-histone complexes and associated proteins released from activated neutrophils. While NET formation plays an important role in innate immunity, it is also associated with the pathogenesis of autoimmune disorders such as rheumatoid arthritis, psoriasis and systemic lupus erythematosus. Research suggests that NETosis (the process of NET formation) may contribute to the progression of cancer and the spread of malignant tumours. A clear link exists between the accumulation of neutrophils in the tumour microenvironment (TME), known as tumour-associated neutrophils (TANs) and NETosis activation in both primary and metastatic tumours. Furthermore, the literature highlights the role of NETs in modulating immune surveillance within the TME. This review aims to analyse the interplay between NETosis and the TME, emphasising its implications for tumour progression, immune evasion and resistance to therapy.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 ","pages":"5568021"},"PeriodicalIF":3.6,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917615","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}
Pavla Taborska, Dmitry Stakheev, Katerina Krausova, Jirina Bartunkova, Daniel Smrz
{"title":"High Concentrations of β<sub>2</sub>-Microglobulin Do Not Inhibit In Vitro Generation of Functional Dendritic Cells.","authors":"Pavla Taborska, Dmitry Stakheev, Katerina Krausova, Jirina Bartunkova, Daniel Smrz","doi":"10.1155/jimr/2924555","DOIUrl":"10.1155/jimr/2924555","url":null,"abstract":"<p><p>β<sub>2</sub>-microglobulin (β2M) is a small protein playing a critical role in stabilizing major histocompatibility complex class I (MHC-I) molecules on nucleated cells. Elevated levels of β2M have been observed in several cancers, inflammatory and autoimmune conditions, and renal failures. High concentrations of β2M were reported to inhibit in vitro generation of functional dendritic cells (DCs). However, our findings showed that β2M exerts a negative effect on DCs only when contaminated with endotoxins. We found that β2M preparations with a high level of endotoxin impurities matured DCs, but that this effect was not seen with functional β2M preparations with low levels of endotoxin impurities, thus showing the maturation effect was due to endotoxin stimulation. We confirmed that the high-level endotoxin β2M compromised the in vitro differentiation of monocytes into DCs. In contrast, a low-level endotoxin β2M had no negative impact on DC differentiation nor prevented their maturation and functionality. Moreover, regardless of the levels of endotoxin impurities, β2M stabilized the expression of MHC-I molecules, confirming its functionality in the experimental settings. Our results show that β2M does not compromise the differentiation of DCs and indicate that elevated levels of β2M are unlikely to negatively regulate the immune system. These results have significant implications for understanding the functions of high β2M concentrations in clinical contexts and in vitro applications.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 ","pages":"2924555"},"PeriodicalIF":3.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917596","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}
Julia Westerlund, Sandra Askman, Åsa Pettersson, Stina Wichert, Thomas Hellmark, Åsa C M Johansson, Markus Hansson
{"title":"Myeloid-Derived Suppressor Cells (MDSCs) Suppress T-Cell Proliferation Less Than Mature Neutrophils in Blood and Bone Marrow From Multiple Myeloma Patients.","authors":"Julia Westerlund, Sandra Askman, Åsa Pettersson, Stina Wichert, Thomas Hellmark, Åsa C M Johansson, Markus Hansson","doi":"10.1155/jimr/9232540","DOIUrl":"10.1155/jimr/9232540","url":null,"abstract":"<p><p>Multiple myeloma (MM) is the second most common hematological malignancy, characterized by a clonal expansion of malignant plasma cells in bone marrow. Monoclonal gammopathy of undetermined significance (MGUS) is the premalignant condition of MM. The tumor microenvironment is thought to influence the progression from premalignant conditions. Myeloid-derived suppressor cells (MDSCs) are a heterogenous group of different cellular subsets with myeloid origin, characterized by their ability to inhibit T-cell responses. MDSC are thought to play an important immunoregulatory role in different diseases, and in many cancers their levels seem to correlate with a poor prognosis. There are three different subsets, the neutrophil-like polymorphonuclear (PMN)-MDSC, the monocyte-like (M)-MDSC, and the immature early (e)MDSC. In this study, we investigate the levels and functions of all MDSC subsets in the bone marrow of both MGUS and MM patients and compare it to blood MDSC. We found that MDSC levels are not increased in neither the blood nor bone marrow of MGUS or MM patients, and they lack strong T-cell suppressive abilities. Blood PMN-MDSC seems to have a small inhibitory effect, but mature neutrophils were more suppressive. Interestingly, eMDSC levels were decreased in the blood of MM patients. Our data indicate that MDSC are not key players in the pathogenesis of MM, but that mature neutrophils may be more important as they have a stronger immunoregulatory effect.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 ","pages":"9232540"},"PeriodicalIF":3.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917568","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}
Marina Barrio-Calvo, Astrid Sissel Muldorff Frellsen, Emma Probst Brandum, Mette Marie Rosenkilde, Eoghan Connors, Per Basse, Pawel Kalinski, Gertrud Malene Hjortø
{"title":"An Exploratory Study of the Impact of a CCL21-Derived C-Terminal Peptide on Dendritic Cell Lymph Node Homing.","authors":"Marina Barrio-Calvo, Astrid Sissel Muldorff Frellsen, Emma Probst Brandum, Mette Marie Rosenkilde, Eoghan Connors, Per Basse, Pawel Kalinski, Gertrud Malene Hjortø","doi":"10.1155/jimr/8833079","DOIUrl":"10.1155/jimr/8833079","url":null,"abstract":"<p><p>The effective trafficking of dendritic cells (DCs) to the lymph nodes (LNs), orchestrated by CC-chemokine receptor 7 (CCR7) and its ligand CCL21, is essential for the success of DC-based immunotherapies. This study explores the potential of C21TP, a naturally occurring basic peptide derived from the C-terminal of CCL21, to enhance DC homing to the draining LNs in a murine model of DC migration. C21TP, containing three clusters of basic residues, significantly boosts CCL21-mediated signaling and chemotaxis of DCs in vitro. In vivo, DCs formulated with C21TP prior to injection migrated more efficiently to the draining LNs than DCs alone or DCs formulated with a mutated version of C21TP, harboring substitutions in key basic residues. Further studies are needed to evaluate the impact of C21TP on T-cell priming efficacy in the context of DC-based immunotherapies. Nonetheless, C21TP's ability to enhance lymph node homing of adoptively transferred cells without additional cellular modifications could offer a practical and scalable approach for advancing future DC-based vaccines.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 ","pages":"8833079"},"PeriodicalIF":3.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917573","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}
Dianne Celine Gnann, Stephan Steinke, Hendrikus S P Garritsen, Michael Hust
{"title":"Resolving the Interference of Anti-CD38 Antibodies on Blood Compatibility Assays Using CD38 \"Baitbodies\" Approach.","authors":"Dianne Celine Gnann, Stephan Steinke, Hendrikus S P Garritsen, Michael Hust","doi":"10.1155/jimr/7343647","DOIUrl":"10.1155/jimr/7343647","url":null,"abstract":"<p><p>Blood transfusion safety depends on swift blood compatibility testing. Alloantibodies recognizing these blood group antigens determine blood compatibility, and the transfusion of incompatible blood can lead to life-threatening hemolytic transfusion reactions. Recently, the landscape of blood compatibility testing has been complicated due to the interference caused by therapeutic antibodies targeting CD38, a key target in cancer immunotherapy that is also expressed on red blood cells. The presence of anti-CD38 antibodies in blood samples has been found to bind to test or donor red blood cells, resulting in false positive tests. This interference poses a serious risk as it can potentially mask immunogenic alloantibodies and cause delays in supplying safe blood products. We present the development and application of fragment crystallizable (Fc)-fusion constructs, referred to as \"baitbodies\", designed to neutralize anti-CD38 antibodies and mitigate false positive test outcomes. The extracellular domain of CD38 was fused to the Fc domain of a murine immunoglobulin G. These baitbody constructs were thoroughly characterized and applied in both serological microcolumn agglutination and automated solid-phase red cell adherence assays. The CD38-mFc baitbody successfully prevented agglutination reactions induced by three clinically relevant anti-CD38 monoclonal antibodies-daratumumab, felzartamab and isatuximab-in spiked samples. This allowed the detection of alloantibodies of the Rhesus, Kell and Duffy blood groups without interference. The CD38-mFc construct also demonstrated potential in a head-to-head comparison with commercial mitigation reagents, DaraEx and Grifols sCD38. Finally, the CD38-mFc baitbody effectively neutralized daratumumab in patient samples, preventing false positive test outcomes.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 ","pages":"7343647"},"PeriodicalIF":3.6,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12765988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911983","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}
{"title":"Immune System and Hepatic Stellate Cells' Crosstalk in Liver Fibrosis: Pathways and Therapeutic Potential.","authors":"Wahyu Widowati, Adilah Hafizha Nur Sabrina, Annisa Firdaus Sutendi, Fadhilah Haifa Zahiroh, Aris Muhamad Nurjamil, Teresa Liliana Wargasetia, Ita Margaretha Nainggolan, Rizal Azis, Elham Rismani, Massoud Vosough","doi":"10.1155/jimr/2656395","DOIUrl":"10.1155/jimr/2656395","url":null,"abstract":"<p><p>Liver fibrosis, characterized by the excessive deposition of extracellular matrix (ECM) driven by hepatic stellate cells (HSCs) activation, remains a critical challenge due to its progression to cirrhosis and hepatocellular carcinoma (HCC). This review clarifies the complex crosstalk between the immune system and HSCs, highlighting key cellular players including macrophages, natural killer (NK) cells, regulatory T cells (Tregs), and their cytokine-mediated signaling pathways that regulate fibrogenesis and fibrosis resolution. We describe pivotal molecular mechanisms such as transforming growth factor (TGF)-β, platelet-derived growth factor (PDGF), Wnt/β-catenin, and NF-κB signaling in HSCs modulation, emphasizing their interplay with immune responses. Novel therapeutic strategies targeting this complex immune-HSCs interaction, ranging from immunomodulatory agents, macrophage polarization, and NK cell-based therapies, to stem cell-derived exosomes, offer promising opportunities for preventing and reversing fibrosis. We further discuss innovative combination therapies integrating immunotherapies with antifibrotic agents, personalized strategies based on immune profiling, and the challenges of immune heterogeneity in fibrosis management. This review discusses recent advances in molecular interplay of immune system and HSCs, highlighting novel therapeutic targets, and future perspectives for managing chronic liver diseases.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 ","pages":"2656395"},"PeriodicalIF":3.6,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12759114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900559","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}
{"title":"Pilot Study to Improve In Vitro Identification of Culprit Drugs in SJS/TEN Using Granzyme B and Granulysin Secretion Assays.","authors":"Yuttana Srinoulprasert, Somkiat Ud-Naen, Tunsuda Tansit, Papapit Tuchinda, Chamard Wongsa, Jettanong Klaewsongkram","doi":"10.1155/jimr/8497493","DOIUrl":"https://doi.org/10.1155/jimr/8497493","url":null,"abstract":"<p><strong>Introduction: </strong>Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions (SCARs) with high morbidity and mortality. Accurate identification of the culprit drug is critical and remains challenging, whereas current in vitro tests such as lymphocyte transformation test (LTT) have limited sensitivity. To evaluate measuring granulysin (Gr) and granzyme B (GZB) secretion from drug-stimulated peripheral blood mononuclear cells (PBMCs) for identification of culprit drugs and to compare their diagnostic performance with conventional LTT.</p><p><strong>Materials and methods: </strong>PBMCs from 12 patients with confirmed SJS/TEN were incubated with suspected drugs. LTT and Gr/GZB detection assays were performed on day 3 and 6. Levels of Gr and GZB were quantified from supernatants, and results were normalized as production ratios. Cut-off values were defined using receiver operating characteristic (ROC) curve analysis with high specificity thresholds.</p><p><strong>Results: </strong>GZB detection on day 3 yielded the highest sensitivity (8/12) compared to LTT (6/12) and Gr detection. Combining GZB and Gr detection improved the positive rate to 10/12. ROC curve analysis demonstrated higher AUCs for cytokine assay than for LTT, particularly for GZB at day 3. Combining GZB and Gr detection with LTT did not significantly increase diagnostic yield.</p><p><strong>Conclusion: </strong>The detection of GZB and Gr production in PBMC cultures provided a more sensitive and specific method than the conventional LTT for identifying culprit drugs in SJS/TEN. In particular, GZB detection at day 3 provided a shorter assay duration, avoided radioactive labeling, and demonstrated superior diagnostic performance. This cytokine-based approach may represent a practical and safer alternative to enhance drug causality assessment in patients with SCARs.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e8497493"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654022","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}
Hiroyuki Tsuchiya, Takehiko Hanaki, Mayu Obora, Jun Yoshida, Mikiya Kishino, Yoshiyuki Fujiwara, Daisuke Nanba
{"title":"High-Throughput Heterospheroid-Based Screening Identifies Drugs That Reprogram Tumor-Associated Macrophages.","authors":"Hiroyuki Tsuchiya, Takehiko Hanaki, Mayu Obora, Jun Yoshida, Mikiya Kishino, Yoshiyuki Fujiwara, Daisuke Nanba","doi":"10.1155/jimr/2889509","DOIUrl":"10.1155/jimr/2889509","url":null,"abstract":"<p><p>The tumor microenvironment (TME) provides a niche for immune evasion and immunotherapy resistance, in part, by recruiting pro-tumor M2-like macrophages. In the present study, using heterospheroids consisting of cancer cells and macrophages, we identified TAM activators, which are compounds that reprogram M2-like tumor-associated macrophages (TAMs) toward the antitumor M1-like phenotype. THP-1- or human peripheral monocyte-derived macrophages were co-cultured with liver cancer (LC) cells in an ultra-low attachment dish to generate heterospheroids. Cell surface marker expression and macrophage infiltration into the heterospheroids were assessed by flow cytometry and fluorescence microscopy, respectively. Lipopolysaccharide (LPS) and interferon-γ (IFNγ)-induced M1 marker expression was observed on the macrophages in the homospheroids; however, this induction was suppressed in heterospheroids. Microscopic imaging revealed that macrophage infiltration into the heterospheroids was decreased in the presence of LPS and IFNγ, which prompted us to develop a high-content imaging screen. We identified two compounds [alprostadil (prostaglandin E1) and HX531] with TAM-activating activity. RNA-seq analysis revealed that HX531 modulated the immune and IFN response in cancer cells and cell division in macrophages. Moreover, alprostadil promoted the M1-like polarization of TAMs, increased tumor-infiltrating CD8<sup>+</sup> T cells, and enhanced anti-PD-1 antibody therapeutic efficacy in a syngeneic tumor-bearing mouse. In conclusion, the heterospheroid culture recapitulates the immunosuppressive TME, which prevents the M1 polarization of TAMs. It provides a new platform for screening TAM activators and will enable the development of novel cancer immunotherapeutics when combined with high-content imaging analysis.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e2889509"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728969","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}
{"title":"Immunophenotypic Stratification of Primary Sjögren's Syndrome Reveals Distinct Lymphocyte Profiles and Clinical Manifestations.","authors":"Yimeng Jia, Sicheng Huang, Ye Guo, Anqi Wang, Chuiwen Deng, Yunyun Fei","doi":"10.1155/jimr/9295560","DOIUrl":"10.1155/jimr/9295560","url":null,"abstract":"<p><strong>Objective: </strong>Primary Sjögren's syndrome (pSS) is a heterogeneous autoimmune disorder with diverse clinical manifestations and limited effective therapies. This study aimed to stratify pSS patients into distinct immunophenotypic subgroups based on peripheral lymphocyte profiles and to explore the clinical relevance of these subgroups, thereby informing personalized management for pSS.</p><p><strong>Methods: </strong>A retrospective cohort of 133 Chinese pSS patients and 241 age- and sex-matched healthy controls (HCs) was analyzed. Immunophenotyping of 11 lymphocyte subsets was performed using flow cytometry in peripheral blood. K-means clustering was employed to identify patient subgroups based on lymphocyte profile. Clinical data were collected and compared across clusters.</p><p><strong>Results: </strong>Lymphocyte profiles in pSS patients differed from those in HCs, featuring elevated proportions and estimated counts of activated CD8<sup>+</sup> T cells along with reduced naïve CD4<sup>+</sup> T cells and NK cells. Unsupervised clustering analysis identified three distinct patient subgroups based on immunophenotypic patterns: Cluster 1 was characterized by significantly higher proportions of CD8<sup>+</sup> T cells and showed more frequent hematologic and serological abnormalities, including higher rates of hyperglobulinemia, anti-Ro52 positivity, and high-titer ANA positivity. Cluster 2 was distinguished by higher NK and B cell proportions and clinically presented with greater pulmonary and hepatic involvement along with higher disease damage scores. Cluster 3 maintained lymphocyte distributions closest to HCs but exhibited more frequent constitutional symptoms and cutaneous involvement coupled with lower serological activity.</p><p><strong>Conclusion: </strong>Lymphocyte profiling may help stratify pSS patients into clinically distinct subgroups, potentially corresponding to different pathobiological endotypes, and could thus inform patient stratification.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e9295560"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433530","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}