bims-actimu 2024-12-01 papers

Issue of 2024–12–01
two papers selected by
Elodie Busch, University of Strasbourg

Front Med. 2024 Nov 29.

Recurrent eosinophilia with a novel homozygous ARPC1B mutation.

Gamze Sonmez, Baris Ulum, Ates Kutay Tenekeci, Canan Caka, Ali Şahin, Alp Kazancıoğlu, Begum Ozbek, İsmail Yaz, Saliha Esenboğa, Deniz Çağdaş.

Cytoskeletal network dysregulation is a pivotal determinant in various immunodeficiencies and autoinflammatory conditions. This report reviews the significance of actin remodeling in disease pathogenesis, focusing on the Arp2/3 complex and its regulatory subunit actin related protein 2/3 complex subunit 1B (ARPC1B). A spectrum of cellular dysfunctions associated with ARPC1B deficiency, impacting diverse immune cell types, is elucidated. The study presents a patient featuring recurrent and persistent eosinophilia attributed to homozygous ARPC1B mutation alongside concomitant compound heterozygous cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. We used ARPC1B antibody to stain the patient's peripheral blood lymphocytes and those of the control. The defect in the ARPC1B gene in the present patient caused absent/low expression by immunofluorescence microscopy. The intricate interplay between cytoskeletal defects and immunological manifestations underscores the complexity of disease phenotypes, warranting further exploration for targeted therapeutic strategies.

Keywords: ARPC1B deficiency; actin cytoskeleton defects; cystic fibrosis; hypereosinophilia; primary immunodeficiency

DOI: https://doi.org/10.1007/s11684-024-1106-2

J Clin Immunol. 2024 Nov 25. 45(1): 49

Inborn Error of WAS Presenting with SARS-CoV-2-Related Multisystem Inflammatory Syndrome in Children.

Enrico Drago, Francesca Fioredda, Federica Penco, Ignazia Prigione, Arinna Bertoni, Genny Del Zotto, Paola Bocca, Erika Massaccesi, Marina Lanciotti, Daniele Moratto, Lorenz Thurner, Roberta Caorsi, Marco Gattorno, Stefano Volpi.

Multisystem inflammatory syndrome in children (MIS-C) has been reported in patients with inborn errors of immunity (IEI), providing insights into disease pathogenesis. Here, we present the first case of MIS-C in a child affected by Wiskott-Aldrich syndrome (WAS) gene mutation, elucidating underlying predisposing factors and the involved inflammatory pathways. Genetic analysis revealed a frameshift truncating variant in the WAS gene, resulting in WAS protein expression between mild and severe forms, despite a clinical phenotype resembling X-linked thrombocytopenia (XLT). IL-1β secretion by LPS-stimulated peripheral blood mononuclear cells from patient during MIS-C was lower compared to healthy subjects but increased during follow-up. Conversely, the percentage of ASC (apoptosis-associated speck-like protein containing a CARD) specks in the patient's circulating monocytes during the acute phase was higher than in healthy subjects. The type I interferon (IFN) signature during MIS-C was normal, in contrast to the raised IFN signature measured far from the acute event. This case supports the association of IEI with MIS-C, potentially linked to delayed immune responses to SARS-CoV-2. The XLT phenotype underlies a subclinical immunodysregulation involving the NLRP3 inflammasome and the type-I IFN response.

Keywords: IEI; Inflammasome; Interferon; MIS-C; NLRP3; SARS-CoV-2; WAS; XLT

DOI: https://doi.org/10.1007/s10875-024-01840-4