Soluble immune checkpoint landscape in sickle cell disease links systemic inflammation, autoimmunity, and pain
BackgroundSickle cell disease (SCD) is a chronic condition characterized by inflammation, immune dysregulation, and debilitating pain.AimThis study investigates soluble immune checkpoints (sICPs) and their associations with inflammatory mediators, immune cell profiles, autoantibodies, and clinical o...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Hematology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/frhem.2025.1580009/full |
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| author | Wei Li Andrew Q. Pucka Lina Houran Xiaoqing Huang Candice Debats Brandon A. Reyes Andrew R. W. O’Brien Qigui Yu Ying Wang Ying Wang |
| author_facet | Wei Li Andrew Q. Pucka Lina Houran Xiaoqing Huang Candice Debats Brandon A. Reyes Andrew R. W. O’Brien Qigui Yu Ying Wang Ying Wang |
| author_sort | Wei Li |
| collection | DOAJ |
| description | BackgroundSickle cell disease (SCD) is a chronic condition characterized by inflammation, immune dysregulation, and debilitating pain.AimThis study investigates soluble immune checkpoints (sICPs) and their associations with inflammatory mediators, immune cell profiles, autoantibodies, and clinical outcomes in SCD.MethodPeripheral blood samples from 50 SCD patients and 40 demographic-matched healthy controls (HCs) were analyzed for 37 sICPs, 80 inflammatory mediators, and 18 autoantibodies using multiplex assays, alongside immune cell profiles via flow cytometry. Pain and quality of life (QoL) were assessed through patient-reported outcome measures (PROMs).ResultsTwenty-three sICPs, including arginase-1, BTLA, CD27, CD28, CD47, CD80, CD96, CD134, CD137, CD152, GITR, HVEM, IDO, LAG-3, MICA, MICB, Nectin-2, PD-1, Siglec-7, Siglec-9, TIM-3, TIMD-4, and VISTA, were significantly elevated in SCD patients compared to HCs. These sICPs correlated with multiple proinflammatory mediators (e.g., IL-18), autoantibodies (e.g., MPO), and immune cell activation markers (e.g., CD38/HLA-DR on CD8 T cells). Notably, CD28, CD152, HVEM, and VISTA were strongly associated with systemic inflammation and immune cell activation, while BTLA, LAG-3, PD-1, and CD80 correlated with pain and anxiety scores and QoL.ConclusionThis study highlights complex interactions between sICPs, immune activation, inflammation, and clinical outcomes in SCD, underscoring their potential as biomarkers or therapeutic targets to alleviate inflammation and improve QoL in this challenging clinical population. |
| format | Article |
| id | doaj-art-ce34aa8c360e43b596cb3dc3b38ba0a6 |
| institution | DOAJ |
| issn | 2813-3935 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Hematology |
| spelling | doaj-art-ce34aa8c360e43b596cb3dc3b38ba0a62025-08-20T03:17:55ZengFrontiers Media S.A.Frontiers in Hematology2813-39352025-07-01410.3389/frhem.2025.15800091580009Soluble immune checkpoint landscape in sickle cell disease links systemic inflammation, autoimmunity, and painWei Li0Andrew Q. Pucka1Lina Houran2Xiaoqing Huang3Candice Debats4Brandon A. Reyes5Andrew R. W. O’Brien6Qigui Yu7Ying Wang8Ying Wang9Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Anesthesia, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Anesthesia, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Anesthesia, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Anesthesia, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDivision of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Anesthesia, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United StatesDivision of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United StatesBackgroundSickle cell disease (SCD) is a chronic condition characterized by inflammation, immune dysregulation, and debilitating pain.AimThis study investigates soluble immune checkpoints (sICPs) and their associations with inflammatory mediators, immune cell profiles, autoantibodies, and clinical outcomes in SCD.MethodPeripheral blood samples from 50 SCD patients and 40 demographic-matched healthy controls (HCs) were analyzed for 37 sICPs, 80 inflammatory mediators, and 18 autoantibodies using multiplex assays, alongside immune cell profiles via flow cytometry. Pain and quality of life (QoL) were assessed through patient-reported outcome measures (PROMs).ResultsTwenty-three sICPs, including arginase-1, BTLA, CD27, CD28, CD47, CD80, CD96, CD134, CD137, CD152, GITR, HVEM, IDO, LAG-3, MICA, MICB, Nectin-2, PD-1, Siglec-7, Siglec-9, TIM-3, TIMD-4, and VISTA, were significantly elevated in SCD patients compared to HCs. These sICPs correlated with multiple proinflammatory mediators (e.g., IL-18), autoantibodies (e.g., MPO), and immune cell activation markers (e.g., CD38/HLA-DR on CD8 T cells). Notably, CD28, CD152, HVEM, and VISTA were strongly associated with systemic inflammation and immune cell activation, while BTLA, LAG-3, PD-1, and CD80 correlated with pain and anxiety scores and QoL.ConclusionThis study highlights complex interactions between sICPs, immune activation, inflammation, and clinical outcomes in SCD, underscoring their potential as biomarkers or therapeutic targets to alleviate inflammation and improve QoL in this challenging clinical population.https://www.frontiersin.org/articles/10.3389/frhem.2025.1580009/fullsickle cell diseasesoluble immune checkpointsinflammationautoantibodiessteady-state conditionvaso-occlusive crisis |
| spellingShingle | Wei Li Andrew Q. Pucka Lina Houran Xiaoqing Huang Candice Debats Brandon A. Reyes Andrew R. W. O’Brien Qigui Yu Ying Wang Ying Wang Soluble immune checkpoint landscape in sickle cell disease links systemic inflammation, autoimmunity, and pain Frontiers in Hematology sickle cell disease soluble immune checkpoints inflammation autoantibodies steady-state condition vaso-occlusive crisis |
| title | Soluble immune checkpoint landscape in sickle cell disease links systemic inflammation, autoimmunity, and pain |
| title_full | Soluble immune checkpoint landscape in sickle cell disease links systemic inflammation, autoimmunity, and pain |
| title_fullStr | Soluble immune checkpoint landscape in sickle cell disease links systemic inflammation, autoimmunity, and pain |
| title_full_unstemmed | Soluble immune checkpoint landscape in sickle cell disease links systemic inflammation, autoimmunity, and pain |
| title_short | Soluble immune checkpoint landscape in sickle cell disease links systemic inflammation, autoimmunity, and pain |
| title_sort | soluble immune checkpoint landscape in sickle cell disease links systemic inflammation autoimmunity and pain |
| topic | sickle cell disease soluble immune checkpoints inflammation autoantibodies steady-state condition vaso-occlusive crisis |
| url | https://www.frontiersin.org/articles/10.3389/frhem.2025.1580009/full |
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