Fix Neutropenia (FIXNET): focusing on neutrophil proteases defects which serve as novel diagnostic and therapeutic options.
Childhood neutropenia is a heterogeneous group of immunodeficiency and is characterized by a significantly reduced count of neutrophilic granulocyte. Neutrophils as the most abundant type of white blood cells are an essential part of the innate immune system, they ingest, kill, and digest microbial pathogens.
The current neutropenia diagnosis is based on serial blood morphology test and clinical features such as recurrent infections and mucositis. Distinguishing the molecular basis of the diseases it is not possible at the diagnosis, thus doctors don’t know whether the patient suffers from congenital neutropenia or transient form, resulted from immunological reason e.g. after a viral infection. In that case, the pediatrician ought to postpone protective vaccinations, which leads to over 3,000 cases of unvaccinated children annually in Poland. In congenital neutropenia with genetic defects, there is a need to develop a faster and cheaper method of comprehensive diagnosis and treatment. Nowadays, the mutation of the gene responsible for this disease is unknown in about 30-40% of congenital neutropenia patients.
The main cause of neutrophils deficiency are inhibition of granulocytes maturation, arrest in bone marrow, or molecular defects inducing apoptosis. Neutrophils contain specialized granules that possess many proteins, including specific neutrophilic serine proteases. These proteases are necessary for the maturation and functioning of the entire cell, thus mutations in proteases encoding genes lead to neutrophil defects.
The project involves combining the clinical and genetic data with the biology of neutrophilic serine proteases. The main goals are the search for defects in new genes that cause neutropenia, identification of the protease role in neutrophil disorders, designing a unique diagnostic test, and an effective and safe targeted therapy method based on gene editing.