Multicolor Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases
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Primary immunodeficiency diseases (PIDDs) are rare inherited diseases that impair the human immune system. We established a multicolor flow cytometric assay to comprehensively evaluate the immune status and immunological characteristics of patients with PIDDs.
Fifty-nine normal controls and 75 patients with PIDDs, including X-linked severe combined immunodeficiency (X-SCID), X-linked agammaglobulinemia (XLA), X-linked hyper IgM syndrome (X-HIGM), ataxia telangiectasia (AT), Wiskott-Aldrich syndrome (WAS), hyper IgE syndrome (HIES), and chronic mucocutaneous candidiasis disease (CMCD), were enrolled in this study. Immunophenotyes were evaluated by multicolor flow cytometry using seven different panels that allowed the detection of major leukocyte populations in peripheral blood.
Multicolor flow cytometry revealed distinct leukocyte populations and immunological features of patients with X-SCID, XLA, X-HIGM, AT, WAS, HIES, and CMCD.
Immunophenotyping by multicolor flow cytometry is useful to evaluate immune status and contributes to the diagnosis and management of patients with PIDDs.
KeywordsAtaxia telangiectasia Chronic mucocutaneous candidiasis disease Flow cytometry Hyper IgE syndrome Primary immunodeficiency disease
B cell receptor
chronic mucocutaneous candidiasis disease
double negative T
gain of function
hyper IgE syndrome
kappa-deleting recombination excision circles
loss of function
myeloid dendritic cells
peripheral blood mononuclear cells
plasmacytoid dendritic cells
primary immunodeficiency diseases
recent thymic emigrants
severe combined immunodeficiency
T cell receptor
follicular helper T
T cell receptor excision circles
X-linked hyper IgM syndrome
X-linked severe combined immunodeficiency
We thank the patients and their parents as well as the doctors who provided the samples. We thank Ms. Naomi Terada-Takahashi, Ms. Sae Yasuda, Ms. Yuki Inami, Mr. Yohei Kohno, and Mr. Nakaba Ochiai for their technical assistances. This study was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Ministry of Health, Labour, and Welfare of Japan.
Takehiro Takashima, Miko Okamura, Kohsuke Imai, and Hirokazu Kanegane wrote the manuscript. Takehiro Takashima, Miko Okamura, Tzu-Wen Yeh, Tsubasa Okano, Motoi Yamashita, Keisuke Tanaka, and Akihiro Hoshino performed the flow cytometric analysis and collected the data. Noriko Mitsuiki, Masatoshi Takagi, Eiichi Ishii, and Tomohiro Morio contributed to critical discussion. Kohsuke Imai and Hirokazu Kanegane designed the study.
Compliance with Ethical Standards
All subjects or their guardians provided written informed consent to participate in the study in accordance with the Declaration of Helsinki. This study was approved by the Ethics Committee of the Tokyo Medical and Dental University.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
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