Chronic Granulomatous Disease-Like Presentation of a Child with Autosomal Recessive PKCδ Deficiency.

Autor: Neehus AL; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse, INSERM U1163, Paris, France.; Paris Cité University, Imagine Institute, Paris, France., Tuano K; Department of Pediatrics, Allergy and Immunology Division, The David Clinic, Baylor College of Medicine and Texas Children's Hospital, The Woodlands, TX, USA., Le Voyer T; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse, INSERM U1163, Paris, France.; Paris Cité University, Imagine Institute, Paris, France., Nandiwada SL; Department of Pediatrics, Allergy and Immunology Division, The David Clinic, Baylor College of Medicine and Texas Children's Hospital, The Woodlands, TX, USA., Murthy K; Department of Pediatrics, Allergy and Immunology Division, The David Clinic, Baylor College of Medicine and Texas Children's Hospital, The Woodlands, TX, USA., Puel A; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse, INSERM U1163, Paris, France.; Paris Cité University, Imagine Institute, Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Howard Hughes Medical Institute, New York, NY, USA., Casanova JL; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse, INSERM U1163, Paris, France.; Paris Cité University, Imagine Institute, Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Howard Hughes Medical Institute, New York, NY, USA.; Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France., Chinen J; Department of Pediatrics, Allergy and Immunology Division, The David Clinic, Baylor College of Medicine and Texas Children's Hospital, The Woodlands, TX, USA., Bustamante J; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse, INSERM U1163, Paris, France. jacinta.bustamante@inserm.fr.; Paris Cité University, Imagine Institute, Paris, France. jacinta.bustamante@inserm.fr.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. jacinta.bustamante@inserm.fr.; Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, Paris, France. jacinta.bustamante@inserm.fr.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2022 Aug; Vol. 42 (6), pp. 1244-1253. Date of Electronic Publication: 2022 May 18.
DOI: 10.1007/s10875-022-01268-8
Abstrakt: Background: Autosomal recessive (AR) PKCδ deficiency is a rare inborn error of immunity (IEI) characterized by autoimmunity and susceptibility to bacterial, fungal, and viral infections. PKCδ is involved in the intracellular production of reactive oxidative species (ROS).
Material and Methods: We studied a 5-year old girl presenting with a history of Burkholderia cepacia infection. She had no history of autoimmunity, lymphocyte counts were normal, and no auto-antibodies were detected in her plasma. We performed a targeted panel analysis of 407 immunity-related genes and immunological investigations of the underlying genetic condition in this patient.
Results: Consistent with a history suggestive of chronic granulomatous disease (CGD), oxidative burst impairment was observed in the patient's circulating phagocytes in a dihydrorhodamine 123 (DHR) assay. However, targeted genetic panel analysis identified no candidate variants of known CGD-causing genes. Two heterozygous candidate variants were detected in PRKCD: c.285C > A (p.C95*) and c.376G > T (p.D126Y). The missense variant was also predicted to cause abnormal splicing, as it is located at the splice donor site of exon 5. TOPO-TA cloning confirmed that exon 5 was completely skipped, resulting in a truncated protein. No PKCδ protein was detected in the patient's neutrophils and monocyte-derived macrophages. The monocyte-derived macrophages of the patient produced abnormally low levels of ROS, as shown in an Amplex Red assay.
Conclusion: PKCδ deficiency should be considered in young patients with CGD-like clinical manifestations and abnormal DHR assay results, even in the absence of clinical and biological manifestations of autoimmunity.
(© 2022. The Author(s).)
Databáze: MEDLINE
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