Clinical and genetic features of UNC13D deficiency with hypogammaglobulinemia
BackgroundUNC13D deficiency is the most common form of familial hemophagocytic lymphohistiocytosis (FHL) in Asia. Hypogammaglobulinemia is a rare phenotype observed in both patients with FHL3 and sporadic hemophagocytic lymphohistiocytosis (HLH). Our observations suggest that UNC13D deficiency with...
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Frontiers Media S.A.
2025-08-01
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| author | Linyan Xiong Linyan Xiong Linyan Xiong Linyan Xiong Qin Zhao Qin Zhao Qin Zhao Qian Zhao Qian Zhao Qian Zhao Zhiyong Zhang Zhiyong Zhang Zhiyong Zhang Zhiyong Zhang Yunfei An Yunfei An Yunfei An Yunfei An Xuemei Tang Xuemei Tang Xuemei Tang Xuemei Tang Hirokazu Kanegane Xi Yang Xi Yang Xi Yang Xi Yang Xiaodong Zhao Xiaodong Zhao Xiaodong Zhao Xiaodong Zhao |
| author_facet | Linyan Xiong Linyan Xiong Linyan Xiong Linyan Xiong Qin Zhao Qin Zhao Qin Zhao Qian Zhao Qian Zhao Qian Zhao Zhiyong Zhang Zhiyong Zhang Zhiyong Zhang Zhiyong Zhang Yunfei An Yunfei An Yunfei An Yunfei An Xuemei Tang Xuemei Tang Xuemei Tang Xuemei Tang Hirokazu Kanegane Xi Yang Xi Yang Xi Yang Xi Yang Xiaodong Zhao Xiaodong Zhao Xiaodong Zhao Xiaodong Zhao |
| author_sort | Linyan Xiong |
| collection | DOAJ |
| description | BackgroundUNC13D deficiency is the most common form of familial hemophagocytic lymphohistiocytosis (FHL) in Asia. Hypogammaglobulinemia is a rare phenotype observed in both patients with FHL3 and sporadic hemophagocytic lymphohistiocytosis (HLH). Our observations suggest that UNC13D deficiency with hypogammaglobulinemia presents a distinct clinical phenotype compared to other HLH patients. This finding provides valuable clinical insights and may contribute to a more comprehensive understanding of the disease, highlighting the need for further investigation into its genetic and clinical characteristics.MethodsWe retrospectively analyzed the clinical features of five patients with UNC13D deficiency with hypogammaglobulinemia at our center, along with a literature review. The clinical findings were then compared with those of sporadic HLH patients presenting with hypogammaglobulinemia.ResultsAll patients experienced respiratory infections, with two patients showing recurrent episodes. Seizures were observed in 75% of the patients. HLH-related biomarkers were present in all patients. The four patients who did not undergo allogeneic hematopoietic stem cell transplantation (HSCT), all died. Eight variant sites were identified, with 25% located in exon 9 and another 25% in exon 20. The majority (66.67%) of the variants were found in the region responsible for interaction with RAB27α. UNC13D deficiency with hypogammaglobulinemia was associated with a higher frequency of respiratory manifestations, neurological involvement, and an increased mortality rate.ConclusionsOur study presents the first comprehensive description of the clinical features of UNC13D deficiency with hypogammaglobulinemia. Patients with this condition tend to exhibit more severe clinical manifestations and a poorer prognosis. Allogeneic HSCT may help mitigate immune dysregulation. |
| format | Article |
| id | doaj-art-cfbfcf1c87dc4f98ac8518fca54ea9a7 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-cfbfcf1c87dc4f98ac8518fca54ea9a72025-08-20T03:44:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16285071628507Clinical and genetic features of UNC13D deficiency with hypogammaglobulinemiaLinyan Xiong0Linyan Xiong1Linyan Xiong2Linyan Xiong3Qin Zhao4Qin Zhao5Qin Zhao6Qian Zhao7Qian Zhao8Qian Zhao9Zhiyong Zhang10Zhiyong Zhang11Zhiyong Zhang12Zhiyong Zhang13Yunfei An14Yunfei An15Yunfei An16Yunfei An17Xuemei Tang18Xuemei Tang19Xuemei Tang20Xuemei Tang21Hirokazu Kanegane22Xi Yang23Xi Yang24Xi Yang25Xi Yang26Xiaodong Zhao27Xiaodong Zhao28Xiaodong Zhao29Xiaodong Zhao30Department of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChina International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChina International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChina International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChina International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChina International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChina International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Child Health and Development, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University (TMDU), Tokyo, JapanDepartment of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChina International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChina International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaBackgroundUNC13D deficiency is the most common form of familial hemophagocytic lymphohistiocytosis (FHL) in Asia. Hypogammaglobulinemia is a rare phenotype observed in both patients with FHL3 and sporadic hemophagocytic lymphohistiocytosis (HLH). Our observations suggest that UNC13D deficiency with hypogammaglobulinemia presents a distinct clinical phenotype compared to other HLH patients. This finding provides valuable clinical insights and may contribute to a more comprehensive understanding of the disease, highlighting the need for further investigation into its genetic and clinical characteristics.MethodsWe retrospectively analyzed the clinical features of five patients with UNC13D deficiency with hypogammaglobulinemia at our center, along with a literature review. The clinical findings were then compared with those of sporadic HLH patients presenting with hypogammaglobulinemia.ResultsAll patients experienced respiratory infections, with two patients showing recurrent episodes. Seizures were observed in 75% of the patients. HLH-related biomarkers were present in all patients. The four patients who did not undergo allogeneic hematopoietic stem cell transplantation (HSCT), all died. Eight variant sites were identified, with 25% located in exon 9 and another 25% in exon 20. The majority (66.67%) of the variants were found in the region responsible for interaction with RAB27α. UNC13D deficiency with hypogammaglobulinemia was associated with a higher frequency of respiratory manifestations, neurological involvement, and an increased mortality rate.ConclusionsOur study presents the first comprehensive description of the clinical features of UNC13D deficiency with hypogammaglobulinemia. Patients with this condition tend to exhibit more severe clinical manifestations and a poorer prognosis. Allogeneic HSCT may help mitigate immune dysregulation.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1628507/fullhemophagocytic lymphohistiocytosisfamilial hemophagocytic lymphohistiocytosisUNC13Dhypogammaglobulinemiaantibody deficiency |
| spellingShingle | Linyan Xiong Linyan Xiong Linyan Xiong Linyan Xiong Qin Zhao Qin Zhao Qin Zhao Qian Zhao Qian Zhao Qian Zhao Zhiyong Zhang Zhiyong Zhang Zhiyong Zhang Zhiyong Zhang Yunfei An Yunfei An Yunfei An Yunfei An Xuemei Tang Xuemei Tang Xuemei Tang Xuemei Tang Hirokazu Kanegane Xi Yang Xi Yang Xi Yang Xi Yang Xiaodong Zhao Xiaodong Zhao Xiaodong Zhao Xiaodong Zhao Clinical and genetic features of UNC13D deficiency with hypogammaglobulinemia Frontiers in Immunology hemophagocytic lymphohistiocytosis familial hemophagocytic lymphohistiocytosis UNC13D hypogammaglobulinemia antibody deficiency |
| title | Clinical and genetic features of UNC13D deficiency with hypogammaglobulinemia |
| title_full | Clinical and genetic features of UNC13D deficiency with hypogammaglobulinemia |
| title_fullStr | Clinical and genetic features of UNC13D deficiency with hypogammaglobulinemia |
| title_full_unstemmed | Clinical and genetic features of UNC13D deficiency with hypogammaglobulinemia |
| title_short | Clinical and genetic features of UNC13D deficiency with hypogammaglobulinemia |
| title_sort | clinical and genetic features of unc13d deficiency with hypogammaglobulinemia |
| topic | hemophagocytic lymphohistiocytosis familial hemophagocytic lymphohistiocytosis UNC13D hypogammaglobulinemia antibody deficiency |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1628507/full |
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