bims-actimu 2025-04-27 papers

Issue of 2025–04–27
two papers selected by
Elodie Busch, University of Strasbourg

Clin Immunol. 2025 Apr 22. pii: S1521-6616(25)00079-8. [Epub ahead of print] 110504

A novel hemizygous nonsense variant in DOCK11 causes systemic inflammation and immunodeficiency.

Abdulwahab Elsayed, Sandra von Hardenberg, Faranaz Atschekzei, Paul Siek, Torsten Witte, Georgios Sogkas, Felix C Ringshausen.

Hemizygous germline loss-of-function variants in DOCK11, the gene encoding the dedicator of cytokinesis 11 (DOCK11) have been recently identified to cause variable immunodeficiency and immune dysregulation. Features of immune dysregulation have been reported in all so far identified male patients with damaging variants in DOCK11, commonly manifesting with autoimmune cytopenias, inflammatory bowel disease, benign lymphoproliferation and systemic inflammation. In this study, we identified a novel variant in DOCK11 (c.3754C > T, p.(Q1252*)), leading to loss of protein expression, in a patient with a history of recurrent pneumonia, bronchiectasis, infection-triggered hyperinflammation and persistent systemic inflammation. Reevaluation of all previously identified patients and the current case, reveals that variants leading to the complete loss of DOCK11 expression and consequently function rather associate with autoinflammation and recurrent pneumonias, while missense variants, primarily associate with autoantibody-related autoimmune features.

Keywords: Actinopathy; Autoinflammation; Bronchiectasis; DOCK11; DOCK11 deficiency; IgG subclass deficiency; Immunodeficiency; Inborn errors of immunity

DOI: https://doi.org/10.1016/j.clim.2025.110504

BMC Pediatr. 2025 Apr 22. 25(1): 315

Leukocyte adhesion deficiency type III in an infant presenting with intestinal perforation and low percentage of natural killer cells: first case report from Iran.

Zahra Chavoshzadeh, Samin Sharafian, Samin Alavi, Minoo Ahmadinejad, Negar Shams, Fatemeh Malek, Mohammad Saberi.

BACKGROUND: Leukocyte adhesion deficiency III (LAD III) is a very rare autosomal recessive primary immunodeficiency characterized by recurrent infections without pus formation and bleeding syndrome of Glanzmann-type and life-threatening infections. The main etiology of this condition is variations in the FERMT3 gene, which encodes kindlin-3, an integrin-binding protein. We present a toddler with unique symptom of intestinal perforation followed by prolonged bleeding due to Glanzmann-like thrombasthenia who was diagnosed as LAD-III.
CASE PRESENTATION: This report presents a toddler with leukocyte adhesion deficiency type III (LAD III), who was diagnosed because of protracted surgical wound and gastrointestinal bleeding following surgery for small bowel perforation at the age of 16 months. The patient's history was positive for febrile episodes after vaccinations, recurrent pulmonary infections, frequent severe epistaxis and ecchymotic purpuric lesions since early infancy. The presence of severe bleeding symptoms encouraged us to consider LAD III. Accordingly, sanger sequencing was performed which identified that the patient was homozygote for mutation in exon 14 of FERMT3 gene, the gene encoding for kindlin-3. Our patient also showed low percentages of CD16 and CD56 on peripheral blood flow cytometry, an unheard finding in LAD type III.
CONCLUSIONS: LAD III should be considered in differential diagnosis of any child with recurrent infections, persistent leukocytosis, and bleeding disorders. This is the first case of LAD III presenting with intestinal perforation. The present case also showed low percentage of natural killer cells which should be followed in further studies.

Keywords: Case report; FERMT3 gene; Glanzmann-like thrombasthenia; Kindlin-3; LAD type III; Leukocyte adhesion deficiency (LAD); Natural killer cells; Platelet dysfunction

DOI: https://doi.org/10.1186/s12887-025-05674-w