bims-actimu Biomed News
on Actinopathies in inborn errors of immunity
Issue of 2024‒02‒18
two papers selected by
Elodie Busch, University of Strasbourg
  1. Clinical, immunological, and genetic description of a Mexican cohort of patients with DOCK8 deficiency.
  2. A unique STK4 mutation truncating only the C-terminal SARAH domain results in a mild clinical phenotype despite severe T cell lymphopenia: Case report.
  1. Pediatr Allergy Immunol. 2024 Feb;35(2): e14073
    Clinical, immunological, and genetic description of a Mexican cohort of patients with DOCK8 deficiency.
    Eduardo Liquidano-Perez, Gibert Maza-Ramos, Bethy Alexandra Perez Arias, Saul Oswaldo Lugo Reyes, Tania Barragan Arevalo, Sara Alejandra Solorzano-Morales, Edna Venegas Montoya, Aidé Tamara Staines-Boone, Rogelio Guzmán Cotaya, Satoshi Okada, Capucine Picard, Etienne Patin, Nideshda Ramirez-Uribe, Juan Carlos Bustamante-Ogando, Selma Cecilia Scheffler-Mendoza, Marco Antonio Yamazaki-Nakashimada, Marimar Saez-de-Ocariz, Sara Elva Espinosa Padilla, Maria Edith Gonzalez-Serrano.
      PURPOSE: We aimed to describe the clinical, immunological, and genetic features of patients with DOCK8 deficiency (DOCK8-Def) in a tertiary care center for children.METHODS: Retrospective chart review of patients' clinical, immunological, and genetic characteristics with DOCK8-Def. Genetic analysis was performed with targeted- or whole-exome sequencing; we also assessed DOCK8 protein expression and a lymphoproliferation assay and analyzed survival by the Kaplan-Meier method.
    RESULTS: We described 11 patients from 8 unrelated kindreds. The median age at symptoms' onset was 10 months (range 1-54 months). The median follow-up time was 53.4 months (4.8-118.8). All patients presented eczema and recurrent sinopulmonary and cutaneous infections. Besides those symptoms, the most frequent manifestations were bronchiectases (8/11), food allergies (6/11), and severe infections (6/11). Infrequent characteristics were detection of CMV in bronchial lavage, C. parvum-driven sclerosing cholangitis, Takayasu vasculitis, neurological syndromes, pulmonary tuberculosis, and lymphomatoid granulomatosis.
    CONCLUSION: DOCK8-Def has a broad spectrum of manifestations, including allergy, autoimmunity, inflammation, infection, and cancer. The hallmark of this inborn error of immunity is IEI-associated eczema with eosinophilia and increased IgE. Here, we report six new mutations causing human DOCK8 deficiency and symptoms previously unrecognized to occur in DOCK8-Def. Therefore, an early diagnosis of DOCK8-Def is essential to facilitate an adequate treatment such as HSCT.
    Keywords:  DOCK8 protein; eczema; hyper-IgE syndrome; immunodeficiency-associated eczema; immunologic deficiency syndromes
    DOI:  https://doi.org/10.1111/pai.14073
  2. Front Immunol. 2024 ;15 1329610
    A unique STK4 mutation truncating only the C-terminal SARAH domain results in a mild clinical phenotype despite severe T cell lymphopenia: Case report.
    Bandar Al-Saud, Huda Alajlan, Hibah Alruwaili, Latifa Almoaibed, Amer Al-Mazrou, Hazem Ghebeh, Monther Al-Alwan, Anas M Alazami.
      Mutations in STK4 (MST1) are implicated in a form of autosomal recessive combined immunodeficiency, resulting in recurrent infections (especially Epstein-Barr virus viremia), autoimmunity, and cardiac malformations. Here we report a patient with an atypically mild presentation of this disease, initially presenting with severe T cell lymphopenia (< 500 per mm3) and intermittent neutropenia, but now surviving well on immunoglobulins and prophylactic antibacterial treatment. She harbors a unique STK4 mutation that lies further downstream than all others reported to date. Unlike other published cases, her mRNA transcript is not vulnerable to nonsense mediated decay (NMD) and yields a truncated protein that is expected to lose only the C-terminal SARAH domain. This domain is critical for autodimerization and autophosphorylation. While exhibiting significant differences from controls, this patient's T cell proliferation defects and susceptibility to apoptosis are not as severe as reported elsewhere. Expression of PD-1 is in line with healthy controls. Similarly, the dysregulation seen in immunophenotyping is not as pronounced as in other published cases. The nature of this mutation, enabling its evasion from NMD, provides a rare glimpse into the clinical and cellular features associated with the absence of a "null" phenotype of this protein.
    Keywords:  NGS; SARAH domain; case report; lymphopenia; primary immunodeficiency
    DOI:  https://doi.org/10.3389/fimmu.2024.1329610
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