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



Whole-exome sequencing, validated by Sanger sequencing, was performed after extensive investigations.



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.



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.
Gastroenterology and Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address: tawfikkhoury1@hotmail.com.
Tawfik
T
Khoury
Department of Dermatology and the Center for Genetic Diseases of the Skin and Hair, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Vered
V
Molho-Pessach
Department of Dermatology and the Center for Genetic Diseases of the Skin and Hair, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Yuval
Y
Ramot
Gastroenterology and Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Abu Rmeileh
AR
Ayman
Department of Genetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Orly
O
Elpeleg
Department of Pulmonology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Neville
N
Berkman
Department of Dermatology and the Center for Genetic Diseases of the Skin and Hair, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Abraham
A
Zlotogorski
Gastroenterology and Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Yaron
Y
Ilan
D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy*; D005434:Flow Cytometry; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D019947:Receptors, Interleukin-6 / Q000276:immunology; D013577:Syndrome; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D061067:Antibodies, Monoclonal, Humanized; C508017:IL2RA protein, human; C508600:IL6 protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C502936:tocilizumab
STAT3; autoimmunity; interleukin-6