bims-actimu Biomed News
on Actinopathies in inborn errors of immunity
Issue of 2025–08–24
two papers selected by
Elodie Busch, University of Strasbourg
  1. New insights into Wiskott-Aldrich syndrome: ten novel WAS mutations and their clinical impact in a Brazilian cohort.
  2. First Report of Hematopoietic Stem Cell Transplantation for Children Diagnosed with Wiskott-Aldrich Syndrome in Vietnam.
  1. Front Immunol. 2025 ;16 1585594
    New insights into Wiskott-Aldrich syndrome: ten novel WAS mutations and their clinical impact in a Brazilian cohort.
    Lucas W Santos, Samuel S Medina, Jéssica O Frade-Guanaes, Lúcia H Siqueira, Luiz Gustavo R de Lima, Bruna Chati, Marcos T Nolasco da Silva, Adriana G L Riccetto, Paula Lyra, Ana Carla A M Falcão, Pedro P A Santos, Regina S W Di Gesu, Bianca Stefanello, Gabriela G Yamaguti-Hayakawa, Carmem M S Bonfim, Maria M S Vilela, Margareth C Ozelo.
       Background: Wiskott-Aldrich Syndrome (WAS) is a rare and severe X-linked immunodeficiency disorder characterized by microthrombocytopenia, eczema, and increased susceptibility to infections, autoimmunity, and malignancies. This study aims to explore molecular changes in the WAS gene in Brazilian patients and assess their correlation with clinical manifestations and disease severity.
    Methods: Thirty-one patients from 27 families with thrombocytopenia suspected to have WAS or X-linked thrombocytopenia (XLT) were analyzed. Clinical evaluation, cell morphology analysis, and flow cytometry (when feasible) were performed. DNA samples underwent direct sequencing to identify WAS gene mutations.
    Results: Genomic sequencing identified 17 WAS gene variants, 10 of which were novel, expanding the genetic diversity of the disorder. The most frequent WAS gene variants were primarily frameshift indels that introduced premature stop codons, with five localized in exon 10. While thrombocytopenia and small platelets were prevalent, atypical presentations, including one patient with normal platelet size, were observed. The correlation between genotype and phenotype was complex, as some patients harboring similar mutations demonstrated varying disease severities. Of the 22 confirmed cases, 12 underwent hematopoietic stem cell transplantation (HSCT), while six succumbed to severe disease complications, including opportunistic infections and malignancies.
    Conclusions: The study underscores the need for early molecular diagnosis and tailored treatments, particularly HSCT, which remains the standard curative therapy. Additionally, the findings emphasize the role of genetic variation in predicting disease severity, underlining the importance of personalized medical approaches for WAS patients.
    Keywords:  WAS; WASp mutation; Wiskott-Aldrich syndrome; inborn errors of immunity; thrombocytopenia
    DOI:  https://doi.org/10.3389/fimmu.2025.1585594
  2. J Blood Med. 2025 ;16 373-383
    First Report of Hematopoietic Stem Cell Transplantation for Children Diagnosed with Wiskott-Aldrich Syndrome in Vietnam.
    Le Nguyen-Ngoc-Quynh, Binh Nguyen-Thanh, Anh Thi Van Nguyen, Ha Dang-Thi, Anh Ha-Phuong, Quynh Bui-Thi-Thuy, Huong Le-Thi-Minh, Ngoc Nguyen-Bao, Minh Le-Duc, Phuong Ha-Thi, Chi Le-Quynh, Mai Nguyen-Thi-Phuong, Tien Ngo-Manh, Lan Bui-Ngoc, Toan Duong-Khanh, Tung Cao-Viet, Dien Tran-Minh.
       Background: Awareness of inborn error immunity, such as Wiskott-Aldrich syndrome (WAS), is still lacking in Vietnam. The shortage of clinical immunologists and transplantation teams lead to poor prognosis for patients.
    Objective: Describe initial data about hematopoietic stem cell transplantation (HSCT) for WAS.
    Methods: Retrospective analyzing 15 procedures on 13 patients at the Vietnam National Children's Hospital from 2020 to 2024.
    Results: The median age at HSCT was 34 months (range: 17-86). Of the patients, 73.3% received myeloablative conditioning based on busulfan, while 26.7% underwent reduced-intensity conditioning. Donor sources included matched sibling donors (MSD, 20.0%), unrelated cord blood (UCB, 33.3%), phenotypically identical family donor (MFD, 6.7%), and mismatched related donors (MMRD, 40.0%). The median stem cell dose was 4.9 × 10^6/kg of the recipient's body weight (range: 0.33 to 10.4 × 10^6/kg). Neutrophil and platelet engraftment occurred at a median of 14 days (range: 10-19) and 48 days (range: 14-143), respectively. By day +30, 73.3% of patients achieved full donor chimerism. One patient experienced graft failure, and another faced graft rejection two months post-transplant, both of whom underwent a second transplant with different donors. The overall survival rate was 92.3% with a median follow-up of 23 months (range: 6-53), with one patient died from chronic graft-versus-host disease (cGVHD). All surviving patients achieved normalization of platelet counts.
    Conclusion: HSCT offers significant benefits to WAS patients, achieving an excellent overall survival rate.
    Keywords:  Wiskott-Aldrich syndrome; hematopoietic stem cell transplantation; inborn error immunity; pediatric; thrombocytopenia
    DOI:  https://doi.org/10.2147/JBM.S528827
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