Utility of Ruxolitinib in a Child with Chronic Mucocutaneous Candidiasis Caused by a Novel STAT1 Gain-of-Function Mutation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F18%3A10377428" target="_blank" >RIV/00216208:11130/18:10377428 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/18:10377428 RIV/00064203:_____/18:10377428 RIV/00064190:_____/18:N0000021

Result on the web

<a href="https://doi.org/10.1007/s10875-018-0519-6" target="_blank" >https://doi.org/10.1007/s10875-018-0519-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10875-018-0519-6" target="_blank" >10.1007/s10875-018-0519-6</a>

Result language

angličtina

Original language name

Utility of Ruxolitinib in a Child with Chronic Mucocutaneous Candidiasis Caused by a Novel STAT1 Gain-of-Function Mutation

Original language description

Signal transducer and activator of transcription 1 gain-of-function (STAT1 GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC). We aim to report the effect of oral ruxolitinib, the Janus kinase (JAK) family tyrosine kinase inhibitor, on clinical and immune status of a 12-year-old boy with severe CMC due to a novel STAT1 GOF mutation. Clinical features and laboratory data were analyzed, particularly lymphocyte subsets, ex vivo IFN gamma- and IFN alpha-induced STAT1, 3, 5 phosphorylation dynamics during the course of JAK1/2 inhibition therapy, and Th17-related, STAT1- and STAT3-inducible gene expression before and during the treatment. Sanger sequencing was used to detect the STAT1 mutation. Literature review of ruxolitinib in treatment of CMC is appended. A novel STAT1 GOF mutation (c.617T &gt; C; p.L206P), detected in a child with recalcitrant CMC, was shown to be reversible in vitro with ruxolitinib. Major clinical improvement was achieved after 8 weeks of ruxolitinib treatment, while sustained suppression of IFN gamma- and IFN alpha-induced phosphorylation of STAT1, STAT3, and STAT5, as well as increased STAT3-inducible and Th17-related gene expression, was demonstrated ex vivo. Clinical relapse and spike of all monitored phosphorylated STAT activity was registered shortly after unplanned withdrawal, decreasing again after ruxolitinib reintroduction. No increase of peripheral CD4(+) IL17(+) T cells was detected after 4 months of therapy. No adverse effects were noted. JAK1/2 inhibition with ruxolitinib represents a viable option for treatment of refractory CMC, if HSCT is not considered. However, long-term administration is necessary, as the effect is not sustained after treatment discontinuation.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30102 - Immunology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Clinical Immunology

ISSN

0271-9142

e-ISSN

—

Volume of the periodical

38

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

589-601

UT code for WoS article

000439737900009

EID of the result in the Scopus database

2-s2.0-85048888376