![]() T cell receptor excision circle (TREC)ĭuring T cell receptor rearrangement, excised DNA fragments create TREC. Also, Human Treg and Tfh cells were detected using monoclonal antibodies in PBMCs. A total of 20 subpopulations were examined to analyze the T and B lymphocyte subsets. Whole blood was used for standard flow cytometry multicolor analysis staining of lymphocyte surface markers was performed after red cell lysis, as described previously. Immunological function analysis Lymphocyte subsets Peripheral blood mononuclear cells (PBMCs) were isolated from freshly drawn heparin-treated blood by Ficoll density gradient centrifugation. Written informed consent was obtained from the patients’ families included in the study. Two patients with ZAP-70 deficiency were recruited from the Children’s Hospital of Chongqing Medical University in 20. Herein, we describe the characteristics of these two patients to extend the range of clinical, genetic, and immunological phenotypes associated with ZAP-70 mutations. So far, a total of two patients have been admitted to our cohort and been successfully treated with hematopoietic stem cell transplantation (HCT). In 2017, we reported the first case of ZAP-70 deficiency in China (Qing Liu et al. Patients with ZAP-70 deficiency often present a history of recurrent opportunistic infections, with autoimmunity, or immune dysregulation such as ulcerative colitis and cytopenia, pustular skin lesions, subcutaneous nodules, lymphoma, Omenn syndrome, and hemophagocytic lymphohistiocytosis (HLH). To date, 49 cases with ZAP-70 deficiency have been reported. Thus, deficiency of ZAP-70 causes a CID phenotype, but slightly milder than those with recessive forms of severe CID (SCID). Activated ZAP-70 regulates motility, adhesion, and cytokine expression of specific lymphocytes. Activation of T cell antigen receptor (TCR) leads to tyrosine phosphorylation of several cellular proteins including Zeta(ζ)-Chain Associated Protein Kinase 70 kDa (ZAP-70), a member of the Syk family (non-receptor protein tyrosine kinase family), that co-precipitates with zeta upon TCR stimulation. It is well known that protein-tyrosine kinases (PTKs) play an integral role in T-cell activation. Ĭombined immunodeficiency (CID), the first IEI classification, is generally characterized by T cell development and/or functional defects. There are now 485 single-gene IEI and 10 main groups of the classification updated by the International Union of Immunological Societies in 2022, underlying phenotypes as diverse as infection, malignancy, allergy, autoimmunity, and autoinflammation. Human inborn errors of immunity (IEI) are caused by monogenic germline mutations resulting in the loss or gain of function of the encoded protein. Hematopoietic stem cell transplantation can provide excellent long-term immune function and resolution of clinical problems. Selective CD8 + T cell loss is an essential feature of the immunophenotype of ZAP-70 deficiency patients, but there are exceptions. These two cases have been treated with hematopoietic stem cell transplantation. Case 2 is the second ZAP-70 patient presenting a normal CD8 + T cell number. Sequencing revealed novel compound heterozygous mutations in ZAP-70 of these patients. Case 1 presented with leaky severe combined immunodeficiency with low to the absence of CD8 + T cells, while case 2 suffered from a recurrent respiratory infection and had a past medical history of non-EBV-associated Hodgkin’s lymphoma. We describe the clinical, genetic, and immunological phenotypes of two patients with ZAP-70 deficiency in China, and the data are also compared with the literature. In this study, we report two patients to extend the range of clinical phenotypes and immunophenotypes associated with ZAP-70 mutations. Zeta(ζ)-Chain Associated Protein Kinase 70 kDa (ZAP-70) deficiency is a rare autosomal recessive primary immunodeficiency disease.
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