Tocilizumab Promotes Regulatory T-cell Alleviation in STAT3 Gain-of-function−associated Multi-organ Autoimmune Syndrome

Tawfik Khoury*, Vered Molho-Pessach, Yuval Ramot, Abu Rmeileh Ayman, Orly Elpeleg, Neville Berkman, Abraham Zlotogorski, Yaron Ilan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Purpose Signal transducer and activator of transcription 3 is a member of a family of proteins involved in the regulation of inflammation, differentiation, proliferation, and survival of cells. Here we describe a 38-year-old male who has experienced gastrointestinal, dermatologic, pulmonary, and malignant manifestations. Methods Whole-exome sequencing, validated by Sanger sequencing, was performed after extensive investigations. Findings Whole-exome sequencing revealed a heterozygous missense mutation in the signal transducer and activator of transcription 3 gene, c.1261G>A (p.G421R). Fluorescence-activated cell sorting analysis of peripheral T lymphocytes revealed low levels of CD4+CD25+FoxP3 and CD8+CD25+FoxP3 regulatory T cells. After treatment with 2 cycles of tocilizumab, an interleukin-6 receptor antibody, a significant increase in the level of regulatory T cells was observed, accompanied by clinical improvement. Implications This case sheds light on the emerging role of signal transducer and activator of transcription 3 gain-of-function mutation in the pathogenesis of autoimmune diseases, and further addresses the therapeutic role of interleukin-6 blocker treatment in this syndrome.

Original languageAmerican English
Pages (from-to)444-449
Number of pages6
JournalClinical Therapeutics
Volume39
Issue number2
DOIs
StatePublished - 1 Feb 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Elsevier HS Journals, Inc.

Keywords

  • STAT3
  • autoimmunity
  • interleukin-6

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