Early and rapid detection of X-linked lymphoproliferative syndrome with SH2D1A mutations by flow cytometry

Zhao, Meina; Kanegane, Hirokazu; Kobayashi, Chie; Nakazawa, Yozo; Ishii, Eizaburo; Kasai, Mikio; Terui, Kiminori; Gocho, Yoshihiro; Imai, Kohsuke; Kiyasu, Junichi; Nonoyama, Shigeaki; Miyawaki, Toshio

doi:10.1002/cyto.b.20552

Cited by 18 publications

(20 citation statements)

References 13 publications

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“…Consistent with these previous reports, we observed that memory (CD45RO + ) CD8 T cells from donors 3 and 4 that display the conventional unimodal pattern of SAP expression with the 1C9-SAP Ab clone also expressed higher levels of SAP in terms of median fluorescence intensity (MFI) (2.5-4 times greater than the [CD45RO 2 ] CD8 T cells) (Supplemental Fig. 2) (29). This trend was repeated when we gated on their IFNg-producing CD8 T cells as the IFN-g + CD45RO + CD8 T cells displayed a higher MFI for SAP compared with IFN-g + CD45RO 2 CD8 T cells (Supplemental Fig.…”

Section: C9-hi Cd8 T Cells Display a Predominantly Memory Phenotypesupporting

confidence: 91%

“…Analyses performed in SLE patients and controls have demonstrated that SAP expression levels are higher in effector/memory CD4 T cells compared with naive CD4 T cells, and a separate study demonstrated that memory T cells harbor a greater proportion of SAP + T cells compared with naive T cells (8,29). Additionally, an examination of cases of spontaneous somatic reversion of the SAP mutations in XLPD-Type 1 patients has shown that this reversion is restricted to the memory CD8 T cell and CD4 T cell subsets (14,16).…”

Section: C9-hi Cd8 T Cells Display a Predominantly Memory Phenotypementioning

confidence: 99%

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Detailed Phenotypic and Functional Characterization of a Rare, Antibody-Dependent SLAM-Associated Protein Expression Pattern

et al. 2020

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SLAM-associated protein (SAP) is an adaptor molecule that facilitates critical effector functions in immune cells, and its deficiency causes X-linked lymphoproliferative disease type 1 in which effector responses directed against EBV are severely compromised. The primary objective of this study was to phenotypically and functionally characterize a rare, CD8 T cell-restricted bimodal SAP expression pattern observed in healthy, human donors with the widely used 1C9-SAP mAb clone. We initially observed this pattern during the clinical validation of our flow cytometry-based assay to diagnose X-linked lymphoproliferative disease type 1 in our laboratory. For this validation study, we used multiparameter flow cytometry to identify cytosolic SAP expression in lymphocyte subsets, and CD8 T cells from the donors displaying the rare SAP expression pattern mentioned above were separately further evaluated by intracellular cytokine and CD107a staining to examine polyfunctionality following PMA/ionomycin and HLA class I allele-restricted EBV peptide epitope-induced T cell activation. Our data revealed that SAP 1C9-hi CD8 T cells clearly displayed higher polyfunctional responses versus SAP 1C9-lo CD8 T cells following PMA/ionomycin stimulation. Furthermore, polyfunctional EBV-specific CD8 T cell responses segregated with the SAP 1C9-hi CD8 T cells and not the SAP 1C9-lo CD8 T cells. Additionally, and rather intriguingly, short-and long-term T cell stimulation selectively diminished the signal for the 1C9-hi subset. Overall, our data suggest that although rare, this unique SAP expression pattern merits further evaluation as it has the potential to provide some insight into fundamental processes as they might relate to host-pathogen dynamics. ImmunoHorizons, 2020, 4: 153-164.

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Section: C9-hi Cd8 T Cells Display a Predominantly Memory Phenotypesupporting

confidence: 91%

Section: C9-hi Cd8 T Cells Display a Predominantly Memory Phenotypementioning

confidence: 99%

Detailed Phenotypic and Functional Characterization of a Rare, Antibody-Dependent SLAM-Associated Protein Expression Pattern

et al. 2020

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“…Twenty‐five patients were diagnosed with FHL, nine with FHL type 2 (FHL2), 16 with FHL type 3 (FHL3) and 29 with EBV‐HLH. Flow cytometric and genetic analyses were performed in six out of nine male patients diagnosed with EBV‐HLH (analyses were performed by Dr. H. Kanegane at Tokyo Medical and Dental University), and X‐linked lymphoproliferative syndrome (XLP) was ruled out (Marsh et al , ; Zhao et al , ; Yang et al , ). The remaining three patients were not screened for XLP.…”

Section: Resultsmentioning

confidence: 99%

Laboratory parameters identify familial haemophagocytic lymphohistiocytosis from other forms of paediatric haemophagocytosis

et al. 2015

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SummaryHaemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of immune dysregulation and is classified as primary or secondary according to the underlying aetiology. The treatment strategies recommended for these two groups differ substantially; however, it is thought to be impossible to predict the underlying causes of HLH using conventional laboratory tests. Recent studies show that serum levels of soluble interleukin-2 receptor (sIL2R) and ferritin are useful for differentiating some forms of HLH. The present study reports that combinations of common laboratory parameters, such as the percentage of total lymphocytes within the peripheral blood leucocyte population, serum levels of lactate dehydrogenase and the sIL2R/ferritin ratio, are useful for identifying patients with familial haemophagocytic lymphohistiocytosis and for differentiating the underlying aetiology of paediatric HLH during the early course of the disease. These findings suggest that the pathogenesis of HLH differs greatly in terms of innate and adaptive immunity depending on the aetiology and may provide a new approach to unravelling the complex pathophysiology underlying this syndrome.

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“…When XLP is suspected, flow cytometric analysis of SAP and XIAP can be performed. 464,465 SAP expression levels correlate well with genetic alterations in SH2D1A; normal XIAP expression despite XIAP mutations is more frequent. Therefore detection of normal protein expression does not exclude the diagnosis of XLP2.…”

Section: Diseases Of Immune Dysregulationmentioning

confidence: 92%

Practice parameter for the diagnosis and management of primary immunodeficiency

Bernstein¹,

Blessing-Moore²,

Khan³

et al. 2015

Journal of Allergy and Clinical Immunology

589

494

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The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly accepted responsibility for establishing the "Practice parameter for the diagnosis and management of primary immunodeficiency." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.

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Early and rapid detection of X-linked lymphoproliferative syndrome with SH2D1A mutations by flow cytometry

Cited by 18 publications

References 13 publications

Detailed Phenotypic and Functional Characterization of a Rare, Antibody-Dependent SLAM-Associated Protein Expression Pattern

Detailed Phenotypic and Functional Characterization of a Rare, Antibody-Dependent SLAM-Associated Protein Expression Pattern

Laboratory parameters identify familial haemophagocytic lymphohistiocytosis from other forms of paediatric haemophagocytosis

Practice parameter for the diagnosis and management of primary immunodeficiency

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