Clinical and immunological Characteristics of 10 X-linked Chronic Granulomatous Disease Female Carriers

Background and Aims Chronic granulomatous disease (CGD) is a rare inherited disorder with affected neutrophil “respiratory burst” due to defective NADPH-oxidase function. The most common form, X-linked CGD, is associated with disease manifestations also in female carriers. Increased susceptibility to infections is observed in females with skewed X-chromosome inactivation. Additionally, carriers have increased risk of autoimmunity. Methods We analyzed clinical manifestations, evaluated respiratory burst on neutrophils (%burst), and performed lymphocytes immunophenotyping in a cohort of 10 CGD carriers (aged 26-46 years, median = 41 years). Results Autoimmune disorders and infections observed in 3/10 and 2/10 females, correspondently. Discoid lupus, rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome were described. 6/10 were asymptomatic; 1 female has both infections and autoimmune complications. %Burst varies from 16% to 90% (median = 38.5%): 18-72% in females with autoimmunity, 18-22 with infections, and 16-90% asymptomatic. Thus, all carriers with infections have decreased %burst, but %burst decrease does not necessarily lead to infectious manifestations. %Burst correlates with the number of switched (CD19+CD27+IgD-) and non-switched (CD19+CD27+IgD+) memory B cells (r = 0.75 and 0.68, p = 0.0001 and 0.0009), DN B cells (CD19+CD27-IgD-), and CD21 low CD38 low B cells (r = -0.76, p = 0.0001). Carriers with autoimmunity have decreased NKT cells (p = 0.04) and have a tendency to increase naïve CD4 (CD4+CD45RA+CCR7+) and CD8 (CD8+CD45RA+CCR7+) T cells and RTE (CD4+CD45RA+CD31+) (statistical significance was not reached due to small sample size). However, lymphocyte subsets usually associated with autoimmune disorders in PID (Tregs, activated/memory T cells, and CD21 low B cells) did not differ in carriers with autoimmunity from those in asymptomatic careers. Conclusions Increased susceptibility to infections and B-memory cells differentiation in X-CGD female carriers are concerned with a % of neutrophils with normal NADPH-oxidase function.