bims-actimu 2025-08-17 papers

Issue of 2025–08–17
three papers selected by
Elodie Busch, University of Strasbourg

J Clin Immunol. 2025 Aug 11. 45(1): 122

The Immunodeficiency Profile of Lymphocytes in the Patient with Moesin Gene Mutation During Different Infection.

Qian Liu, Ai Zhang, Yuxin Bai, Xinpu Yang, Xinglou Liu, Lu Yang, Yanqin Ying, Xiaoping Luo, Feng Fang, Chaohong Liu.

PURPOSE: The Ezrin-Radixin-Moesin (ERM) family member moesin (MSN) plays a crucial role in reversibly linking F-actin to the cell membrane. Patients carrying MSN gene mutations consistently exhibit immunodeficiencies. However, due to the scarce number of reported cases worldwide, the mechanism by which MSN mutation leads to immune function defects remains unclear. This study aims to profile the immunological features in MSN mutant patients elaborately.
METHODS: In this article, we present a case study of a patient with c.511 C > T, p.Arg171Trp (p.R171W) mutation on the MSN gene. We analyzed abnormalities in peripheral immune cell subsets by quantitative analysis, morphological examination, and functional molecule assessment during various infection states. Using total internal reflection fluorescence microscopy (TIRFm), we visualized BCR clusters and F-actin dynamics in B cells, revealing valuable insights into B cell activation and the link between F-actin aggregation and BCR signaling in MSN mutant patients.
RESULTS: The results suggest that the MSN c.511 C > T, p.Arg171Trp (p.R171W) mutation affects the proliferation, differentiation, metabolism, and adhesion functions in peripheral immune cells, as well as the maturation process in bone marrow cells. Additionally, we elucidate the impact of MSN mutation on B cell and T cell metabolism and propose a potential diagnostic indicator for patients with MSN gene mutations.
CONCLUSION: Our findings support the diagnosis of primary immunodeficiency and provide detailed insights into changes occurring in immune cells, especially B cells. Overall, our study adds to the diagnosis and pathogenesis of X-linked moesin-associated immunodeficiency (X-MAID).

Keywords: B Cell; BCR; F-actin; Immunodeficiency; Moesin; X-MAID

DOI: https://doi.org/10.1007/s10875-025-01899-7

Pediatr Allergy Immunol. 2025 Aug;36(8): e70171

Novel compound heterozygous MRTFA gene variants cause multiple dysfunctions of neutrophils and autoinflammation.

Wendao Li, Lu Yang, Lang Yu, Rui Gan, Ge Lv, Wenjing Tang, Lina Zhou, Yunfei An, Zhiyong Zhang, Xuemei Tang, Yanan Li, Xiaodong Zhao.

BACKGROUND: Compound heterozygous mutations in the MRTFA gene have not been reported; the complete clinical phenotypic spectrum associated with MRTFA deficiency remains undefined. Whether such mutations can result in autoinflammatory manifestations is also yet to be determined.
METHODS: Comprehensive analyses were conducted on a patient with novel compound heterozygous MRTFA variants, encompassing clinical data collection, genetic validation, and functional studies. Functional assays included protein stability assessment, SRF transcriptional activity measurement, and neutrophil functional evaluation. Lymphocyte profiling was performed using flow cytometry. Transcriptomic alterations in neutrophils and PBMCs were examined through bulk RNA-sequencing.
RESULTS: The patient presented with early-onset infections, rashes, and bloody stools, accompanied by neutropenia and thrombocytopenia. Whole-exome sequencing identified two novel heterozygous nonsense mutations in MRTFA (Q377X/C684X), which caused the absence of MKL1 protein expression and reduced cytoskeletal protein levels. Both mutants presented protein instability and impaired SRF transcriptional activation. F-actin content was reduced in various cell types from the patient. Neutrophils from the patient showed impaired F-actin polymerization, decreased migration ability, reduced ROS production, increased apoptosis, diminished NETs formation, and decreased MPO levels. Transcriptome profiling revealed neutrophil-specific downregulation of cytoskeletal genes with concomitant upregulation of antimicrobial peptide/inflammatory pathways, while PBMCs presented upregulated adhesion/migration-related genes.
CONCLUSION: This study identifies the first reported case with compound heterozygous mutations in the MRTFA gene. The patient demonstrated a milder infectious phenotype but with marked neutrophil dysfunction and prominent autoinflammatory features. This study expands the disease spectrum of MKL1 deficiency and highlights the broader impacts of MKL1 deficiency on neutrophil function and immune regulation.

Keywords: MKL1 deficiency; cytoskeleton; inborn error of immunity; neutrophil defects

DOI: https://doi.org/10.1111/pai.70171

Indian J Pediatr. 2025 Aug 12.

Screening for Wiskott-Aldrich Syndrome in Chronic Idiopathic Thrombocytopenic Purpura.

Pradeep Deivasigamani, Suprit Basu, Rashmi Rikhi, Kanika Arora, Vibhu Joshi, Richa Jain, Amit Rawat, Surjit Singh, Deepti Suri.

The clinical spectrum of X-linked thrombocytopenia (XLT)/ Wiskott-Aldrich syndrome (WAS) is broad, ranging from mild, intermittent thrombocytopenia to the classical severe phenotype characterized by eczema, infections, and thrombocytopenia. Patients with XLT often lack the complete triad but manifest with thrombocytopenia-associated bleeding and are hence misdiagnosed as chronic immune thrombocytopenia (ITP). Moreover, the clinical picture is further complicated by the development of autoimmune cytopenia. Early identification is critical, as definitive treatment with hematopoietic stem cell transplantation (HSCT) can be offered, and unnecessary immunosuppressive therapies, including corticosteroids, can be avoided. In this study, the authors screened a cohort of boys with chronic ITP using flow cytometry-based WASp protein expression analysis, followed by genetic testing. Among 38 patients evaluated, 5 (13.5%) had pathogenic variants in the WAS gene. Clinical features such as X-linked family history, eczema, low mean platelet volume (MPV), or reduced WASp expression in chronic ITP patients with suboptimal response to immunomodulatory drugs should prompt genetic evaluation for WAS.

Keywords: Chronic idiopathic thrombocytopenic purpura; Eczema; Genetics; Screening; Wiskott-Aldrich syndrome

DOI: https://doi.org/10.1007/s12098-025-05712-6