bims-actimu 2025-02-23 papers

Issue of 2025–02–23
two papers selected by
Elodie Busch, University of Strasbourg

Blood. 2025 Feb 19. pii: blood.2024026763. [Epub ahead of print]

Immunoactinopathies revisited: Understanding clinical manifestations and biological pathways.

Fleur Hiensch, Loic Dupre, Elisabeth Salzer.

Immune cell functionality is highly dependent on the actin cytoskeleton. The actin cytoskeleton is regulated by a complex molecular machinery, involving multiple genes. Mutations in these genes can cause inborn errors of immunity, also termed immunoactinopathies, of which Wiskott Aldrich Syndrome is the best-characterized entity. At present, mutations in 23 genes can be considered causative of immunoactinopathies. Immunoactinopathies are rare disease entities with complex combinations of clinical manifestations, including immunodeficiency, immune dysregulation, malignancies, atopy, thrombocytopenia and bleeding, skin involvement or congenital defects. Prompt diagnosis is of crucial importance, as HSCT in an early phase can offer cure and prevent further complications. This review provides a detailed summary of the clinical experience with immunoactinopathies so far, elaborates on the most distinguishing features among immunoactinopathies by providing a clinical categorization, and links this information to the biological pathways that are involved. This information may be of help for clinicians to diagnose patients and eventually improve patient care.

DOI: https://doi.org/10.1182/blood.2024026763

Front Immunol. 2025 ;16 1495666

Haploidentical stem cell transplantation with posttransplant cyclophosphamide in children with Wiskott-Aldrich syndrome: a case report.

Le Nguyen Ngoc Quynh, Binh Nguyen Thanh, Lien Luong Thi, Thuy Nguyen Thi Dieu, Duong Dang Anh, Pamela P Lee, Tung Cao Viet, Dien Tran Minh.

Wiskott-Aldrich syndrome (WAS) is a condition characterized by a low platelet count, eczema, and a weakened immune system. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option. Haploidentical HSCT with posttransplant cyclophosphamide (PTCy) is an emerging approach for children with noncancerous conditions. This case describes a WAS patient who was early diagnosed and successfully treated with haploidentical HSCT. A 3-month-old boy presented with widespread eczema, a low platelet count, and severe infections in infancy. The diagnosis of WAS was quickly confirmed by genetic test. He received immunoglobulin replacement therapy and antimicrobial prophylaxis and underwent HSCT at 4 years 3 months of age. After failed unrelated cord blood HSCT, second rescue haploidentical HSCT had been performed using the patient's mother as the donor, with stem cells collected from peripheral blood. The conditioning regimen included anti-thymocyte globulin, melphalan, and fludarabine. The stem cell dose was 2.63 × 106 CD34+ cells/kg. GVHD prevention included PTCy, mycophenolat mofetil, and tacrolimus. The patient had no significant complications after the transplant. Neutrophil and platelet engraftment occurred promptly. At 32 months post-HSCT, the patient had complete hematological and immune reconstitution, with full donor chimerism and no GVHD. In conclusion, the PTCy approach to haploidentical HSCT was a safe and effective treatment for this WAS patient.

Keywords: Wiskott–Aldrich syndrome; hematopoietic stem cell transplantation; inborn error immunity; posttransplant cyclophosphamide; thrombocytopenia

DOI: https://doi.org/10.3389/fimmu.2025.1495666