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Efficacy of tocilizumab therapy in a patient with severe pancytopenia associated with a STAT3 gain-of-function mutation
- Source :
- BMC Immunology, Vol 22, Iss 1, Pp 1-9 (2021), BMC Immunology
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Background We aimed to report the clinical characteristics, immunological features, and treatment of one patient with a de novo STAT3 gain-of-function mutation identified by next generation sequencing. We investigated the efficacy of tocilizumab therapy in immune dysregulation diseases caused by STAT3 mutation. Results The patient was a 16-year-old girl. She presented with recurrent respiratory infections and chronic diarrhea after birth. She had life-threatening autoimmune pancytopenia at 14 years old. After receiving glucocorticoid therapy, she developed diabetes. However, her pancytopenia relapsed when the glucocorticoid was tapered. Next-generation sequencing showed a de novo heterozygous mutation in the STAT3 gene, c.1261G > A (p. G421R), which was previously described as a gain-of-function mutation. After tocilizumab therapy, her pancytopenia fully resolved, and insulin and glucocorticoid therapies were gradually discontinued within 12 months. She had lymphopenia and an inverted CD4/CD8 ratio before therapy. Lymphocyte subpopulation analysis indicated an expansion of effector memory CD4+, effector memory CD8+ and central memory CD4+ T cells. The proportions of memory B cells and naive CD4+ T cells were decreased, and the proportion of naïve B cells was increased. None of the abnormal lymphocytic changes improved significantly. STAT3 GOF mutations were identified by next gene sequencing in those with early-onset multi-organ autoimmunity. Including our patient, 13 patients with STAT3 GOF mutations received targeted treatment. Twelve of them were treated with tocilizumab alone or combination tocilizumab with JAK inhibitor, and ten patients improved. Conclusions Gene sequencing should be performed for patients with early-onset refractory or multiorgan immune dysregulation diseases. Targeted drugs can effectively improve the clinical problems associated with STAT3 gain-of-function mutations, while nontargeted immunosuppressive therapy is usually insufficient.
- Subjects :
- lcsh:Immunologic diseases. Allergy
Adolescent
Pancytopenia
T-Lymphocytes
Lymphocyte
Immunology
Naive B cell
Antibodies, Monoclonal, Humanized
medicine.disease_cause
Autoimmunity
STAT3 GOF
chemistry.chemical_compound
Tocilizumab
medicine
Humans
STAT3 transcription factor
B-Lymphocytes
Interleukin-6
business.industry
Immune dysregulation
medicine.disease
Lymphocyte Subsets
Immune Dysregulation
Treatment Outcome
medicine.anatomical_structure
chemistry
Gain-of-function mutations
Gain of Function Mutation
Female
business
lcsh:RC581-607
Glucocorticoid
Research Article
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 14712172
- Volume :
- 22
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Immunology
- Accession number :
- edsair.doi.dedup.....3959372abb40d21e8665e845983a0fc5