Severe RAS-Associated Lymphoproliferative Disease Case with Increasing αβ Double-Negative T Cells with Atypical...

Area of Science:

• Immunology
• Hematology
• Genetics

Background:

• Autoimmune lymphoproliferative syndrome (ALPS) involves lymphocyte homeostasis defects and increased TCRαβ+CD4-CD8- double-negative T cells (αβDNTs).
• RAS-associated leukoproliferative disease (RALD) encompasses disorders from KRAS/NRAS variants, presenting similar clinical courses.

Observation:

• A 7-year-old Japanese female with RALD due to an NRAS variant developed juvenile myelomonocytic leukemia (JMML).
• This patient exhibited increased αβDNTs without FAS pathway mutations, distinguishing it from typical ALPS.
• The patient experienced recurrent shock episodes, attributed to the high αβDNT count.

Findings:

• The observed αβDNTs expressed high CCR4, CCR6, and CD45RO, resembling Th17 cells.
• These Th17-like αβDNTs likely induced inflammation and shock through pro-inflammatory cytokine secretion (e.g., IL-17A).
• The patient also had systemic lupus erythematosus (SLE), suggesting a potential link between Th17-like αβDNTs and autoimmune pathogenesis.

Implications:

• This case highlights a potential mechanism for shock in RALD via Th17-like αβDNTs.
• Understanding αβDNT characteristics in RALD, JMML, and ALPS could elucidate disease pathologies.
• Further research into Th17-like αβDNTs may offer insights into inflammatory and autoimmune conditions like SLE.