bims-actimu 2025-09-14 papers

Issue of 2025–09–14
three papers selected by
Elodie Busch, University of Strasbourg

Nat Rev Immunol. 2025 Sep 10.

Loïc Dupré, Irinka Castanon, Kaan Boztug.

Actin cytoskeleton remodelling drives the migration of immune cells and their engagement in dynamic cell-cell contacts. The importance of actin cytoskeleton dynamics in immune cell function is highlighted by the discovery of inborn errors of immunity (IEIs) that are caused by defects in individual actin-regulatory proteins, resulting in immune-related actinopathies. In addition to susceptibility to infection, these often present with a vast array of autoimmune and autoinflammatory manifestations. Here, we review the role of actin subnetworks in the activation and function of lymphoid and myeloid cells. We focus on the mechanisms by which actin defects result in aberrant lymphocyte function, including dysregulation of T cell- and B cell-mediated tolerance and biased cytokine production, which can result in autoimmunity. We also highlight the relationship between actin defects and inflammasome activation and other pathomechanisms in myeloid cells as the underlying cause of autoinflammation. Finally, we discuss future avenues for research and therapeutic intervention based on a molecular understanding of immune-related actinopathies.

DOI: https://doi.org/10.1038/s41577-025-01214-w

Am J Hematol. 2025 Sep 08.

Comorbidities in Mild WAS/XLT Require Lifelong Follow-Up and Consideration of Definitive Treatment.

Members of the CEREDIH French PID Study Group

Loss of function mutations in the gene encoding WASP (Wiskott-Aldrich syndrome protein) result in Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia-XLT (WAS/XLT). The clinical severity of the disease can be assessed using the WAS clinical severity score. Typically, patients with a score of 3 or less at 2 years of age are considered to have mild WAS/XLT disease. However, patients with a low score in the first 2 years of life can still experience life-threatening complications, and there are no agreed guidelines for the management of these patients with mild WAS/XLT. We analyzed data on WAS/XLT patients from the French National Reference Centre for Primary Immunodeficiencies registry. At 10 December 2021, data were available for 261 patients, 170 of whom had mild WAS/XLT. The median age of these patients at last follow-up was 15.8 years (range 2.0-60.4). Overall survival at 40 years was 73% in mild WAS patients versus 65% in severe WAS patients (p = 0.43). In the mild WAS population, prior to Hematopoietic Stem Cell Transplantation or gene therapy, 38.2% of patients progressed to a WAS severity score of 4-5 after the age of 2. Remarkably, no deaths were reported in 45 HSCTs performed since 2010, regardless of initial severity, type and HLA compatibility of the transplant, and age at diagnosis, with a median follow-up of 3.2 years (0-11.5) after transplant. As complications can occur throughout life, our study supports definitive treatment for all patients when available, including those with mild forms.

Keywords: Wiskott‐Aldrich syndrome (WAS); X‐linked thrombocytopenia; hematopoietic stem cell transplantation; primary immunodeficiency

DOI: https://doi.org/10.1002/ajh.70061

Allergol Immunopathol (Madr). 2025 ;53(5): 138-142

Wiskott-Aldrich syndrome complicated with IgG4-related Sclerosing disease: A case report and literature review.

Seda Altiner, Makbule Seda Bayrak Durmaz.

Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency characterized by eczema, microthrombocytopenia, and recurrent infections. Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder involving various organs. We present a 34-year-old male with WAS who developed cervical lymphadenopathy and parotid gland swelling. Initial biopsies were inconclusive and imaging suggested pleomorphic adenoma. Given the persistent cervical lymphadenopathy and the underlying immunodeficiency, lymphoma was also considered in the differential diagnosis. However, histopathological examination of excised salivary gland and lymph nodes revealed lymphoplasmacytic and eosinophilic infiltrates, numerous IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis, consistent with IgG4-RD. The patient responded well to prednisone therapy. This case emphasizes the importance of considering IgG4-RD in the differential diagnosis of lymphoproliferative lesions in immunodeficient individuals and highlights the diagnostic value of histopathological evaluation in excisional tissue specimens. To our knowledge, this represents a rare coexistence of WAS and IgG4-RD not previously reported in the literature.

Keywords: IgG4-related disease; Wiskott-Aldrich Syndrome; lymphadenomegaly; rare disease

DOI: https://doi.org/10.15586/aei.v53i5.1437