Mannose-binding lectin was identified as an important part of natural human immunity and a basic protein activating the lectin complement pathway. Mutations in the promotor and coding area of MBL2 gene are known to lead to significant decreases in serum MBL concentration which might be connected with immunodeficiency manifestation in young age [24]. Infections have been described as a potential trigger of oedema formation in HAE patients [25]. One could speculate that MBL gene mutations could positively influence the HAE phenotype becasue of lower MBL potential to
complement activation, which could mean a lowered find more disposition to triggering the complement cascade and oedema development after infectious stimulus in patients with C1 Inh deficiency. However, Cedzynski et al. [26] did not find any relationship between the HAE phenotype and MBL levels and ability of MBL to activate complement, respectively. Our study, which considered a number of varied parameters characterizing a course of the disease, also did not find any evidence on MBL involvement in HAE clinical manifestation. In conclusion, examination of particular functional polymorphisms in BDKR1, BDKR2, ACE and MBL2 genes did not support a hypothesis about the potential
disease-modifying role of these genes on the HAE phenotype. It seems likely that other genetic and/or environmental factors are responsible for HAE clinical variability in Caucasians. However, it has to be emphasized that the study was performed on a limited number of heterogenous patients and therefore
with a limited power of performed MK0683 manufacturer MycoClean Mycoplasma Removal Kit analyses. Becasue of a heterogeneous nature of the disease and its rare occurrence, it seems to be difficult to collect sufficiently large amount of homogeneous HAE patients for powerful analysis in a single country. It is noteworthy that comparable numbers of patients were used also in other studies addressing the influence of genetic factors on HAE clinical manifestation [7, 8, 14, 26]. Evidently, only a large international multicentre study could bring powerful results targeting these topics. We thank Lenka Suchankova for the technical help. The study was supported by the grants Nos. NR7921-3 and NR9192-3 of the Internal grant agency of the Ministry of Health, Czech Republic. Table S1 Frequency of BDKR1, BDKR2, ACE, and MBL2 gene polymorphisms and mutations in HAE patients and control individuals. Table S2 Association of HAE clinical score and gene variants in the BDKR1, BDKR2, ACE, and MBL2 genes in all HAE patients. Table S3 Association of HAE disease severity, frequency of attacks and disease onset with analysed gene variants in the BDKR1, BDKR2, ACE, and MBL2 genes in all HAE patients. “
“OTHER ARTICLES PUBLISHED ON ANCA IN THIS ISSUE Animal models of anti-neutrophil cytoplasmic antibody-associated vasculitis. Clinical and Experimental Immunology 2012, 169: 229–37.