- Immune thrombocytopenia and systemic lymphoproliferative syndrome as primary clinical manifestations of combined immunodeficiency associated with CTLA-4 deficiency
Immune thrombocytopenia and systemic lymphoproliferative syndrome as primary clinical manifestations of combined immunodeficiency associated with CTLA-4 deficiency
Modern Pediatrics. Ukraine. (2025).5(149): 132-142. doi: 10.15574/SP.2025.5(149).132142
Dorosh O. I.1,2, Kurylekh M. A.1, Tymchyshyn S. M.1, Yavorska O. T.1
1СNE of Lviv Regional Council «Western Ukrainian Specialized Pediatric Medical Centre», Ukraine
2Danylo Halytsky Lviv National Medical University, Ukraine
For citation: Dorosh OI, Kurylekh MA, Tymchyshyn SM, Yavorska OT. (2025). Immune thrombocytopenia and systemic lymphoproliferative syndrome as primary clinical manifestations of combined immunodeficiency associated with CTLA-4 deficiency. Modern Pediatrics. Ukraine. 5(149): 132-142. doi: 10.15574/SP.2025.5(149).132142.
Article received: May 02, 2025. Accepted for publication: Sep 10, 2025.
Severe combined immunodeficiency (SCID) associated with CTLA-4 deficiency is a rare serious genetic immunological disorder caused by mutations in the CTLA-4 gene. A characteristic feature of this immunodeficiency is systemic lymphoproliferative syndrome (LPS), infiltration of internal organs by lymphoid cells and autoimmune cytopenias, among which immune thrombocytopenia (ITP) may be the first or even the sole clinical manifestation in the early stages of the disease, which significantly complicates diagnosis. The disease often presents itself in childhood or adolescence. The wide variability of phenotypic manifestations in patients significantly complicates and delays the diagnostic process.
Aim – to describe a clinical case of SCID associated with CTLA-4 deficiency with a combination of ITP and systemic LPS.
Clinical case. A 1,5-year-old girl with progressive systemic lymphadenopathy, hepatosplenomegaly, thrombocytopenia, frequent infections from an early age was found to have decreased IgA, IgM, IgG, B-memory cells, the presence of ANA antibodies, and a positive direct Coombs test. Genetic testing confirmed the presence of pathogenic variants in the genes: CTLA-4 (with autosomal dominant CTLA-4 deficiency – immune dysregulation, autoimmunity, lymphoproliferation) and CORO1A (autosomal recessive severe combined immunodeficiency).
Conclusions. The initial manifestations of SCID are often nonspecific, which can delay the final diagnosis. The combination of LPS and ITP in childhood should be considered a potential manifestation of primary immunodeficiency. CTLA-4-SCID is a rare clinical case that requires increased oncological and immunological vigilance. Early detection of CTLA-4 deficiency through immunological and molecular genetic diagnosis is critical for timely treatment and prevention of serious complications. Іt is important that physicians of various specialties consider congenital immunodeficiencies among the possible causes during the differential diagnosis diseases.
The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
Keywords: іmmune thrombocytopenia, systemic lymphoproliferative syndrome, heterozygous CTLA-4 gene mutation, severe combined immunodeficiency, children.
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