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Two novel kindreds with autosomal recessive STAT2 deficiency
Verena Kienapfel1, Lotte Cresens1, Lucy Bizien2,3
1Laboratory of Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium.
Journal of Human Immunity
|July 1, 2026
Summary
STAT2 deficiency, a rare genetic disorder, causes severe viral infections and hyperinflammation. Novel mutations were identified in three patients who experienced adverse reactions to the measles-mumps-rubella (MMR) vaccine, highlighting the need for early diagnosis and targeted therapies.
Area of Science:
- Immunology
- Genetics
- Virology
Background:
- STAT2 is crucial for the type I/III interferon antiviral response.
- Autosomal recessive STAT2 deficiency leads to severe viral infections and hyperinflammation.
- Previous reports identified 12 kindreds with STAT2 deficiency globally.
Purpose of the Study:
- To report three new patients with novel homozygous STAT2 mutations.
- To describe their clinical manifestations, particularly adverse reactions to the MMR vaccine.
- To evaluate treatment strategies for hyperinflammation in STAT2 deficiency.
Main Methods:
- Genetic sequencing to identify STAT2 mutations (K490Qfs*41 and c.941+1G>T).
- Assessment of STAT2 protein expression and function in patient-derived cells.
- Clinical evaluation of patients, including response to vaccinations and treatments.
Main Results:
- Three patients from Portugal and Algeria presented with novel homozygous STAT2 mutations.
- All patients experienced complications after live attenuated MMR vaccination, including hemophagocytic lymphohistiocytosis (HLH) in one case.
- Mutant alleles resulted in non-detectable and non-functional STAT2 proteins, with impaired response to type I IFNs.
- One patient responded to treatment with IVIG, steroids, and ruxolitinib for HLH.
Conclusions:
- STAT2 deficiency should be considered in patients with severe adverse reactions to MMR vaccination.
- Targeted anti-inflammatory drugs like ruxolitinib show promise in managing hyperinflammation.
- Long-term prophylaxis with antibiotics and antifungals, or IVIG, is effective in maintaining patient health.
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