Correlation between flow cytometry and molecular findings in autosomal recessive chronic granulomatous disease: A...

Chronic granulomatous disease (CGD) is an X-linked (XL) or autosomal recessive (AR) primary immunodeficiency disease. Respiratory burst assessment by flow cytometry is a rapid test of granulocyte stimulation, and results predict the underlying genotype. This study aims to describe the immune-phenotypic profile of patients with CGD diagnosed in our center and correlate that with underlying genetic mutations.

Immuno-phenotypic and genetic data on all patients with CGD diagnosed at Sultan Qaboos University Hospital (SQUH) were reviewed.

A total of 32 patients were diagnosed with CGD using molecular studies. Genetically confirmed individuals included 1 patient with XL-CGD (a large deletion involving the CYBB and XK genes resulting in a McLeod phenotype), 27 patients with AR-CGD with a c.579G>A (p.Trp193X) mutation at the NCF1 gene, and 4 patients with AR-CGD with a c.784G>A (p.Gly262Ser) mutation at the NCF1 gene. Flow cytometry and molecular results were available for comparison in 26 patients with AR-CGD. The patients with AR-CGD had a range of flow cytometry-generated fluorescent patterns as follows: reduced neutrophil stimulation with a sharp peak (12/26), reduced neutrophil stimulation with a broad peak (11/26), and a complete lack of neutrophil stimulation (3/26). No consistent flow cytometry-generated fluorescent pattern was observed in either of the 2 AR mutations identified in our patients.

Flow cytometry is a robust test of CGD diagnosis. However, results should be interpreted with caution when predicting the underlying probable genotype, and results need to be complemented with definitive molecular studies.