Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns
BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune dysregulation. Early initiation of treatment is imperative for saving lives. However, a laboratory approach that could be used to quickly evaluate the HLH subtype and clinical situation is lacking. Our pre...
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| Format: | Article |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.850443/full |
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| author | Xiao-Jun Xu Xiao-Jun Xu Ze-Bin Luo Ze-Bin Luo Hua Song Hua Song Wei-Qun Xu Wei-Qun Xu Jan-Inge Henter Jan-Inge Henter Ning Zhao Ning Zhao Meng-Hui Wu Meng-Hui Wu Yong-Min Tang Yong-Min Tang |
| author_facet | Xiao-Jun Xu Xiao-Jun Xu Ze-Bin Luo Ze-Bin Luo Hua Song Hua Song Wei-Qun Xu Wei-Qun Xu Jan-Inge Henter Jan-Inge Henter Ning Zhao Ning Zhao Meng-Hui Wu Meng-Hui Wu Yong-Min Tang Yong-Min Tang |
| author_sort | Xiao-Jun Xu |
| collection | DOAJ |
| description | BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune dysregulation. Early initiation of treatment is imperative for saving lives. However, a laboratory approach that could be used to quickly evaluate the HLH subtype and clinical situation is lacking. Our previous studies indicated that cytokines such as interferon (IFN)-γ and interleukin (IL)-10 were helpful for the early diagnosis of HLH and were associated with disease severity. The purpose of this study is to clarify the different cytokine patterns of various subtypes of pediatric HLH and to investigate the role of cytokines in a simple evaluation of disease feature.Patients and MethodsWe enrolled 256 pediatric patients with newly diagnosed HLH. The clinical features and laboratory findings were collected and compared among different subtypes of HLH. A model integrating cytokines was established to stratify HLH patients into different clinical groups.ResultsTwenty-seven patients were diagnosed with primary HLH (pHLH), 179 with EBV-HLH, and 50 with other causes. The IL-6, IL-10, and IFN-γ levels and the ratios of IL-10 to IFN-γ were different among EBV-HLH, other infection-associated HLH, malignancy-associated HLH, familial HLH, and X-linked lymphoproliferative disease. Patients with the ratio of IL-10 to IFN-γ >1.33 and the concentration of IFN-γ ≤225 pg/ml were considered to have pHLH, with a sensitivity of 73% and a specificity of 84%. A four-quadrant model based on the two cutoff values was established to stratify the patients into different clinical situations. The HLH subtypes, cytokine levels, treatment regimens, treatment response, and outcomes were different among the four quadrants, with the 8-week mortality from 2.9 ± 2.9% to 21.4 ± 5.5% and the 5-year overall survival from 93.9 ± 4.2% to 52.6 ± 7.1%.ConclusionsDifferent subtypes of HLH present distinct cytokine patterns. IFN-γ and the ratio of IL-10 to IFN-γ are helpful tools to differentiate HLH subtypes. A four-quadrant model based on these two parameters is a useful tool for a simple evaluation of the HLH situation. |
| first_indexed | 2024-12-20T19:11:13Z |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T19:11:13Z |
| publishDate | 2022-02-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-05d15671124e428eaaa846e5a37c756a2022-12-21T19:29:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.850443850443Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine PatternsXiao-Jun Xu0Xiao-Jun Xu1Ze-Bin Luo2Ze-Bin Luo3Hua Song4Hua Song5Wei-Qun Xu6Wei-Qun Xu7Jan-Inge Henter8Jan-Inge Henter9Ning Zhao10Ning Zhao11Meng-Hui Wu12Meng-Hui Wu13Yong-Min Tang14Yong-Min Tang15Division/Center of Pediatric Hematology-Oncology, the Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaThe Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, ChinaDivision/Center of Pediatric Hematology-Oncology, the Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaThe Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, ChinaDivision/Center of Pediatric Hematology-Oncology, the Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaThe Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, ChinaDivision/Center of Pediatric Hematology-Oncology, the Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaThe Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, ChinaChildhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, SwedenPediatric Oncology, Theme of Children’s Health, Karolinska University Hospital, Stockholm, SwedenDivision/Center of Pediatric Hematology-Oncology, the Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaThe Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, ChinaDivision/Center of Pediatric Hematology-Oncology, the Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaThe Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, ChinaDivision/Center of Pediatric Hematology-Oncology, the Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaThe Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Hangzhou, ChinaBackgroundHemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune dysregulation. Early initiation of treatment is imperative for saving lives. However, a laboratory approach that could be used to quickly evaluate the HLH subtype and clinical situation is lacking. Our previous studies indicated that cytokines such as interferon (IFN)-γ and interleukin (IL)-10 were helpful for the early diagnosis of HLH and were associated with disease severity. The purpose of this study is to clarify the different cytokine patterns of various subtypes of pediatric HLH and to investigate the role of cytokines in a simple evaluation of disease feature.Patients and MethodsWe enrolled 256 pediatric patients with newly diagnosed HLH. The clinical features and laboratory findings were collected and compared among different subtypes of HLH. A model integrating cytokines was established to stratify HLH patients into different clinical groups.ResultsTwenty-seven patients were diagnosed with primary HLH (pHLH), 179 with EBV-HLH, and 50 with other causes. The IL-6, IL-10, and IFN-γ levels and the ratios of IL-10 to IFN-γ were different among EBV-HLH, other infection-associated HLH, malignancy-associated HLH, familial HLH, and X-linked lymphoproliferative disease. Patients with the ratio of IL-10 to IFN-γ >1.33 and the concentration of IFN-γ ≤225 pg/ml were considered to have pHLH, with a sensitivity of 73% and a specificity of 84%. A four-quadrant model based on the two cutoff values was established to stratify the patients into different clinical situations. The HLH subtypes, cytokine levels, treatment regimens, treatment response, and outcomes were different among the four quadrants, with the 8-week mortality from 2.9 ± 2.9% to 21.4 ± 5.5% and the 5-year overall survival from 93.9 ± 4.2% to 52.6 ± 7.1%.ConclusionsDifferent subtypes of HLH present distinct cytokine patterns. IFN-γ and the ratio of IL-10 to IFN-γ are helpful tools to differentiate HLH subtypes. A four-quadrant model based on these two parameters is a useful tool for a simple evaluation of the HLH situation.https://www.frontiersin.org/articles/10.3389/fimmu.2022.850443/fullhemophagocytic lymphohistiocytosiscytokinesinterleukin-10interferon-gammaprognosis |
| spellingShingle | Xiao-Jun Xu Xiao-Jun Xu Ze-Bin Luo Ze-Bin Luo Hua Song Hua Song Wei-Qun Xu Wei-Qun Xu Jan-Inge Henter Jan-Inge Henter Ning Zhao Ning Zhao Meng-Hui Wu Meng-Hui Wu Yong-Min Tang Yong-Min Tang Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns Frontiers in Immunology hemophagocytic lymphohistiocytosis cytokines interleukin-10 interferon-gamma prognosis |
| title | Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns |
| title_full | Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns |
| title_fullStr | Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns |
| title_full_unstemmed | Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns |
| title_short | Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns |
| title_sort | simple evaluation of clinical situation and subtypes of pediatric hemophagocytic lymphohistiocytosis by cytokine patterns |
| topic | hemophagocytic lymphohistiocytosis cytokines interleukin-10 interferon-gamma prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.850443/full |
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