bims-actimu 2024-03-31 papers

Issue of 2024–03–31
two papers selected by
Elodie Busch, University of Strasbourg

Pediatr Blood Cancer. 2024 Mar 24. e30972

Wiskott-Aldrich syndrome protein expression in female WAS carriers: A flow cytometry study from North India.

Suprit Basu, Rashmi Rikhi, Kanika Arora, Vibhu Joshi, Saniya Sharma, Amit Rawat, Surjit Singh, Deepti Suri.

INTRODUCTION: Wiskott-Aldrich syndrome (WAS) is a rare X-linked inborn error of immunity characterized by microthrombocytopenia, infections, eczema, and increased predisposition to develop autoimmunity and malignancy. Flow cytometric assay for determining WAS protein (WASp) is a rapid and cost-effective tool for detecting patients. However, very few studies described WASp expression in female carriers. Most WAS carriers are clinically asymptomatic. Active screening of female family members helps identify female carriers, distinguish de novo mutations, and to select appropriate donor prior to curative stem cell transplantation. This study was undertaken to evaluate the diagnostic capability of flow cytometry-based WASp expression in peripheral blood cells to identify carriers and compare WASp expression in different blood cell lineages.
PATIENTS AND METHODS: Female patients, heterozygous for WAS gene, were enrolled in this study conducted at Pediatric Allergy Immunology Unit, Advanced Pediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Flow cytometric assessment of WASp expression in lymphocytes, monocytes, and neutrophils was carried out and compared with healthy control and affected patients. The results were expressed in delta (Δ) median fluorescence intensity (MFI) as well as stain index (SI), which is the ratio of ΔMFI of patient and ΔMFI of control.
RESULTS: Thirteen mothers and two sisters of genetically confirmed WAS patients were enrolled in the study. All enrolled females were clinically asymptomatic and did not have microthrombocytopenia. Low WASp expression (SI < 1) was seen in lymphocytes and monocytes in 10 (66.6%) carriers. Females with variants in proximal exons (exons 1 and 2) were found to have lesser expression than those with distal (exons 3-12) variants.
CONCLUSION: Flow cytometry is a rapid, easily available, cost-effective tool for WASp estimation. Lymphocytes followed by monocytes are the best cell lineages for WASp estimation in carrier females. However, genetic testing remains the gold standard, as carrier females with variants in distal exons may have normal WASp expression.

Keywords: Wiskott–Aldrich syndrome protein; carrier females; genotype; myeloid cell lineages; stain index

DOI: https://doi.org/10.1002/pbc.30972

J Fungi (Basel). 2024 Mar 05. pii: 198. [Epub ahead of print]10(3):

A Novel CARMIL2 Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with Pneumocystis and Bordetella Pneumonia.

Emily L Coffey, Liang Ma, Ousmane H Cissé, Joseph A Kovacs, Katie M Minor, Antti Sukura, Patrizia Danesi, Steven G Friedenberg, Jonah N Cullen, Christiane Weissenbacher-Lang, Julie C Nadeau, Amber M Graham, Martin N Granick, Natalie K Branson, Kyle C Branson, Barbara Blasi, Casandra M Jacobs, Eva Furrow.

Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to Pneumocystis and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for Pneumocystis pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a CARMIL2 nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory Bordetella pneumonia (n = 1). CARMIL2 encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious CARMIL2 variants have recently been reported in human patients with PCP and other recurrent pneumonias. In addition to opportunistic respiratory infection, the affected dogs also exhibited other clinical manifestations of CARMIL2 deficiencies that have been reported in humans, including early-onset gastrointestinal disease, allergic skin disease, mucocutaneous lesions, abscesses, autoimmune disorders, and gastrointestinal parasitism. This discovery highlights the potential utility of a natural canine model in identifying and studying primary immunodeficiencies in patients affected by PCP.

Keywords: CARMIL2; Pneumocystis; canine; combined immunodeficiency; dog; primary immunodeficiency

DOI: https://doi.org/10.3390/jof10030198