Year: 2008
Type: article
Study design: Case Report
Abstract: s of the 15th International Symposium on Infections in the Immunocompromised Host S7tions, recurrent upper and lower respiratory tract infections, and neutropenia.The younger sister had repeated oral infections that ultimately resulted in development of oral strictures.A twin sister of the younger child who had a similar presentation died at age 3 years from a septic event.Objective: To characterize the functional responses of patient neutrophils as a way to identify the underlying immunodeficiency.Methods and Results: Neutrophils from both sisters exhibited normal O2-production to phorbol myristate, fMLF, and cytochalasin B + zymosan.Although degranulation and staphylocidal activity were not dramatically altered, a profound chemotactic defect in vitro was detected.Microscopic examination of purified neutrophils from both sisters showed abnormal nuclear morphology in 40-50% of the cells with herniation of nuclear lobes into plasma membrane-enclosed surface blebs.No abnormal morphology was observed in the neutrophils on routine peripheral blood smears.Electron microscopic examination of isolated cells confirmed abnormal morphology in both neutrophils and eosinophils.Moreover, herniation of nuclear lobes coincided with retraction of the granules into the central region of the cells, resulting in an agranular region in the periphery of the cell.Confocal microscopy, using Alexa Fluor 546-phalloidin to identify filamentous actin and DAPI to localize nuclei, showed that cells with herniated nuclear lobes exhibited increased levels of filamentous actin compared to either patient cells with normal nuclear lobes or to normal neutrophils.Conclusion: Abnormal nuclear morphology, profound chemotactic defect, and cytoskeletal anomaly in these two sisters with recurrent infections represents a novel defect of neutrophils that is likely autosomal recessive.
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,900
OpenAlex ID: W2045343755