PHENOMENON OF BIMODAL EXPRESSION OF WASP IN PATIENTS WITH WISKOTT–ALDRICH SYNDROME ASSESSED BY FLOW CYTOMETRY

Compensatory or revertant somatic mutations (RSM) is a well-known phenomenon in patients with PIs. RSM can lead to the restoration of functional protein expression in some cell populations and thus influence the severity of clinical manifestations in patients with PI. The WAS gene, a mutation that leads to the development of Wiskott–Aldrich syndrome (WAS), is associated with high levels of RSM. In our study, we aimed to describe in detail the RSM phenomenon in patients with WAS, and also to try to study its effect on the severity of the clinical phenotype. Materials and methods of research: a single-center, prospective, open, continuous, non-randomized, comparative study was conducted. The study included 39 male patients with WAS from 2 months and up to 18 years old with mutation in WAS gene, who underwent assessment of WASP expression using flow cytometry. In 2 out of 9 patients, use of magnetic selection made it possible to isolate a population of lymphocytes expressing WASP. Germinal and somatic mutations were identified using Sanger sequencing. To assess severity of clinical manifestations of WAS, the original detailed scoring classification was used. Results: 9 patients had bimodal expression of WASP, which equaled to 23% of all examined. The median age of these patients was 3 years [7 months. – 15 years]. In two patients a presence of RSM was confirmed in WASP-expressing populations. Linear assessment of partially restored WASP expression revealed different patterns of lymphocyte subpopulation involvement in all 9 patients. The effect of RSM on the severity of clinical manifestations of WAS in the studied group of patients was statistically insignificant (p=0,39). Conclusion: according to the data obtained, patients with WAS, demonstrating a bimodal pattern of WASP expression, represent a very heterogeneous group in terms of the severity of clinical manifestations, involvement of cell populations, and the nature of RSM. This work is a methodological prerequisite for further comprehensive study of RSM phenomenon in patients with various PIs.