Two families of X-linked lymphoproliferative disease type 1 characterized by agammaglobulinemia
10.3760/cma.j.issn.0578-1310.2017.05.014
- VernacularTitle: 以丙种球蛋白缺乏血症为突出表现的X连锁淋巴细胞异常增生症1型两家系研究
- Author:
Wenyan LI
1
;
Jinshu CHEN
;
Qin ZHAO
;
Rongxin DAI
;
Yanping WANG
;
Hongyi ZHAO
;
Xuemei CHEN
;
Xiuhong XUE
;
Xiaoyu SUN
;
Xuemei TANG
;
Yu ZHANG
;
Yuan DING
;
Xiaodong ZHAO
;
Zhiyong ZHANG
Author Information
1. Department of Rheumatology and Immunology, Children′s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders. Chongqing Key Laboratory of Child Infection and Immunity, Chongqing 400014, China
- Publication Type:Clinical Trail
- Keywords:
Lymphoproliferative disorders;
Agammaglobulinemia;
Gene, SH2D1A;
Diagnosis
- From:
Chinese Journal of Pediatrics
2017;55(5):377-382
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical and immunological laboratory features, mutations in SH2D1A gene and SAP protein expression in four children of two families with X-linked lymphoproliferative disease type 1(XLP-1).
Method:Four patients (Family A including Patient 1 and Patient 2, Family B including Patient 3 and Patient 4) and their maternal relatives were enrolled in this study. The clinical manifestation, EBV infection status and chest CT scan were analyzed. The absolute and relative numbers of lymphocyte subsets, T lymphocyte proliferative response, SAP protein expression were assessed by flow cytometry. Quantification of signal joint TCR rearrangementexcision circle (sjTRECs), CDR3 spectratyping of TCRvβ and gene mutation of SH2D1A were detected by PCR based on genomic DNA or cDNA.
Result:Four male patients from two families were diagnosed with XLP-1. The ages of disease onset were more than 1 year, more than 1 year, more than 1 month and 6 months. The ages at diagnosis were nine years and ten months, sixteen years and eight months, fourteen years and ten months, four years and nine months. All patients had recurrent infections and EBV infection. Patients 1, 2, and 3 had agammaglobulinemia and Patient 4 had hypogammaglobulinemia. Chest CT scan showed all patients had atelectasis and pneumonia, and Patient 3 had bronchiectasis. Patient 3 was diagnosised as Burkitt lymphoma. For immunological function, all patients exhibited reduced CD4/CD8 ratios, increased numbers of exhausted T lymphocyte, decreased number of NK cell. The numbers of total B lymphocyte and naïve B lymphocyte were normal, but the number of memory B lymphocyte declined in all cases. Four patients′ copy numbers of sjTRECs were low and CDR3 spectratypings of TCRvβ showed mildly skewed. But their T lymphocyte proliferative response was normal. SAP protein expression in four cases were measured by flow cytometry. Two patients from Family A were absent and two patients from Family B showed decreased values. SH2D1A gene sequence analysis showed that the patients of Family A harbored a nonsense mutation (c.163 C>T; p.R55X) in exon 2. Their mother and two sisters were carriers. A missense mutation of SH2D1A gene (c.278 G>A; p.G93D) in exon 3 was found in the patients of Family B. The mother was carrier. Four patients remain survived, Patient 3 gave up treatment, other three patients received IVIG therapy.
Conclusion:Four patients with XLP-1 from two families characterized by agammaglobulinemia have an extreme vulnerability to Epstein-Barr virus (EBV) infection. The functions of T cell, B cell and NK cell are impaired at different stages. The detection of SAP protein and SH2D1A gene are the key methods for diagnosis of XLP-1.
