| Summary: | Kostmann syndrome or severe congenital neutropenia (SCN) is a rare disease, usually diagnosed during the first months of life, characterized by extremely low levels of neutrophils in the peripheral blood, a maturational arrest of the myelopoiesis in the bone marrow and severe bacterial infections. The purpose of this project was to improve the understanding of the clinical course and the pathophysiology of autosomal recessive SCN. Rolf Kostmann presented six patients with autosomal recessive inherited congenital agranulocytosis in a kindred from Överkalix, Norrbotten, Sweden in his thesis 1956 and another ten patients in a review 1975. Today, four patients from this kindred are alive. Initially we described the survivors from a clinical perspective along with a review of the literature regarding the syndrome (I). This review of patients and literature resulted in a number of questions for further investigation. One such question was why the patients still have recurrent infections, particularly periodontal infections, despite normal absolute neutrophil counts (ANC). Functional studies of neutrophils in granulocyte colony-stimulating factor (G-CSF) treated patients with SCN had so far not revealed any major abnormalities. In Paper II we analyzed antibacterial peptides in the patients' neutrophils and found a deficiency of the peptide LL-37 and decreased levels of alpha defensins. No LL-37 could be detected in the saliva of the patients. One of the patients, who had undergone a bone marrow transplantation, had almost normal concentrations of LL-37 and normal dental status, indicating that the degree of peptide deficiency correlated with the severity of the periodontitis. The in vitro efficiency of antibacterial peptides is well documented and we therefore propose an in vivo role of antibacterial peptides in the prevention of bacterial infections in man generally and in patients with SCN in particular. To further elucidate the underlying mechanisms we wanted to see if the maturation block of the myclopoiesis is due ...
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