Details

Autor(en) / Beteiligte

• Haapaniemi, Emma M.
• Kaustio, Meri
• Rajala, Hanna L.M.
• van Adrichem, Arjan J.
• Kainulainen, Leena
• Glumoff, Virpi
• Doffinger, Rainer
• Kuusanmäki, Heikki
• Heiskanen-Kosma, Tarja
• Trotta, Luca
• Chiang, Samuel
• Kulmala, Petri
• Eldfors, Samuli
• Katainen, Riku
• Siitonen, Sanna
• Karjalainen-Lindsberg, Marja-Liisa
• Kovanen, Panu E.
• Otonkoski, Timo
• Porkka, Kimmo
• Heiskanen, Kaarina
• Hänninen, Arno
• Bryceson, Yenan T.
• Uusitalo-Seppälä, Raija
• Saarela, Janna
• Seppänen, Mikko
• Mustjoki, Satu
• Kere, Juha

Titel

Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3

Ist Teil von

• Blood, 2015-01, Vol.125 (4), p.639-648

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of immunodysregulation polyendocrinopathy enteropathy X-linked–like syndrome. Here, we immunologically characterized 3 patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T, and p.K658N, respectively). The patients displayed multiorgan autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B-cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4−CD8−) T cells, and decreased natural killer, T helper 17, and regulatory T-cell numbers. Notably, the patient harboring the K392R mutation developed T-cell large granular lymphocytic leukemia at age 14 years. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity. •Germline activating STAT3 mutations were detected in 3 patients with autoimmunity, hypogammaglobulinemia, and mycobacterial disease.•T-cell lymphoproliferation, deficiency of regulatory and helper 17 T cells, natural killer cells, dendritic cells, and eosinophils were common.