Lab Med Online.  2020 Oct;10(4):334-339. 10.47429/lmo.2020.10.4.334.

The Usefulness of Flow Cytometry for Measuring Phosphorylated Signal Transducer and Activator of Transcription 1 to Diagnose and Manage Chronic Mucocutaneous Candidiasis: A Case Report

• Yoon SJ
• Kwon WK
• Jeong M
• Yeon JH
• Huh HJ
• Lee NY
• Kim YJ
• Kang ES

• KMID: 2512275
• DOI: http://doi.org/10.47429/lmo.2020.10.4.334

Abstract

Autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) is a subtype of CMC caused by gain-of-function (GOF) mutation of the signal transducer and the activator of transcription 1 (STAT1) protein. GOF mutation of STAT1 disrupts Th17 cell differentiation and causes susceptibility to candida infection in mucous membranes. Although genetic testing is crucial to diagnose AD-CMC, a simple and fast diagnostic tool is required for the management and reduction of complications associated with infection. Flow cytometry (FCM) is suggested for the measurement of intracellular phosphorylated STAT1 (pSTAT1) in a stimulated status. Here, we report the application of FCM to show the activation status of STAT signaling in a 24-year-old female patient diagnosed with AD-CMC. Compared to the controls, the patient’s T cells showed increased levels of pSTAT1 after stimulation by interferon-γ and lesser extent of inhibition caused by an inhibitor. To the best of our knowledge, this is the first evaluation of the usefulness of FCM as an alternative diagnostic and monitoring tool of GOF STAT1 in Korea.

Figure

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  Fig. 1 (A) Pathophysiology of the GOF STAT1 mutation and (B) mucocutaneous candidiasis in the 24-year-old female patient (oral thrush (a), candidiasis of the nasal skin (b), and a fingernail (c)).

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  Fig. 2 (A) Expression of pSTAT1 (%) stimulated by IFN-γ and (B) reduction rate of pSTAT1 when treated with ruxolitinib (10 μM, 50 μM, 100 μM, and 250 μM) in the patient in comparison with healthy controls (N=2).

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  Fig. 3 Comparison of the STAT1 phosphorylation and the degree of inhibition stimulated by IFN-γ without or with the presence of 100 μM ruxolitinib between normal controls (N = 2) and the patient.

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