Systemic skewing of peripheral blood leukocyte composition in neurofibromatosis type 1.

Background: The present study aimed to characterize neurofibromatosis type 1 (NF1)-associated alterations in peripheral white blood cell differentials, focusing on overall patterns and sex-related differences. Methods: We analyzed 225 Japanese patients with NF1 (78 males, 147 females) and 87 controls without NF1 (50 males, 37 females). Within each sex, NF1 and control groups were age-matched. Z-scores were calculated to normalize for sex-specific variation. Results: In patients with NF1, Z-scores for the percentages of neutrophils, monocytes, and basophils were increased, whereas those for lymphocytes and eosinophils were decreased. These trends were consistent across both sexes, indicating robust disease-associated alterations. Additional sex-related differences were observed: males showed greater neutrophil increases and more pronounced lymphocyte reductions, whereas females exhibited greater monocyte increases and more marked eosinophil reductions. Conclusion: NF1 is associated with systemic skewing of peripheral immune cell composition, characterized by expansion of the non-type 2/innate component, relative uncoupling of the type 2-associated component, and reduction of the lymphoid component. These findings provide a conceptual basis for understanding NF1 pathobiology, disease heterogeneity, and sex-related differences, including tumor-associated immune environments.