Hereditary angioedema (HAE) is a rare genetic disorder with variable expressivity even in carriers of the same underlying genetic defect, suggesting other genetic and epigenetic factors participate in modifying HAE severity. Recent knowledge indicates the role of immune cells in several aspects of HAE pathogenesis, which makes monocytes and macrophages candidates to mediate these effects. Here we combined a search for HAE phenotype modifying gene variants with the characterization of selected genes' mRNA levels in monocyte and macrophages in a symptom-free period. While no such gene variant was found to be associated with a more severe or milder disease, patients revealed a higher number of dysregulated genes and their expression profile was significantly altered, which was typically manifested by changes in individual gene expression or by strengthened or weakened relations in mutually co-expressed gene groups, depending on HAE severity. SERPING1 showed decreased expression in HAE-C1INH patients, but this effect was significant only in patients carrying mutations supposedly activating nonsense-mediated decay. Pro-inflammatory CXC chemokine superfamily members CXCL8, 10 and 11 were downregulated, while other genes such as FCGR1A, or long non-coding RNA NEAT1 were upregulated in patients. Co-expression within some gene groups (such as an NF-kappaB function related group) was strengthened in patients with a severe and/or mild course compared to controls. All these findings show that transcript levels in myeloid cells achieve different activation or depression levels in HAE-C1INH patients than in healthy controls and/or based on disease severity and could participate in determining the HAE phenotype.

Central European Institute of Technology Masaryk University Brno Czechia

Centre for Cardiovascular Surgery and Transplantation Brno Czechia

Department of Allergology and Clinical Immunology St Anne's University Hospital in Brno Brno Czechia

Department of Experimental Biology Faculty of Science Masaryk University Brno Czechia

Department of Immunology 2nd Medical School Charles University and University Hospital Motol Brno Czechia

Department of Immunology and Allergology Faculty of Medicine in Pilsen Charles University Pilsen Czechia

Department of Immunology and Allergology University Hospital Pilsen Pilsen Czechia

Department of Pulmonology and Phthisiology Jessenius Faculty of Medicine Comenius University in Bratislava University Teaching Hospital in Martin Martin Slovakia

Depatment of Clinical Immunology and Allergology Comenius University in Bratislava Comenius University in Bratislava University Teaching Hospital in Martin Martin Slovakia

Faculty of Medicine Masaryk University Brno Czechia

Institute of Clinical Immunology and Allergy University Hospital Hradec Kralove Charles University Faculty of Medicine in Hradec Kralove Hradec Kralove Czechia

National Centre for Hereditary Angioedema Department of Pediatrics Jessenius Faculty of Medicine Comenius University in Bratislava University Teaching Hospital in Martin Martin Slovakia

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