Fcγ receptor IIA genotype and susceptibility to P. aeruginosa infection in patients with cystic fibrosis

Abstract

It has been suggested that genes other than CFTR could modulate the severity of lung disease in cystic fibrosis (CF). Neutrophil Fcc receptor II (FccRII) is involved in host defense against microorganisms and in inflammatory response. We evaluated the association between genetic variability of this gene and both airway infection with Pseudomonas aeruginosa and severity of lung disease in patients with CF. We studied 167 Italian unrelated patients with CF and 50 control subjects. The distribution of FccRIIA genotypes in CF patients was compared with that in control subjects and the different genotypes were related with the presence or absence of P. aeruginosa infection and markers of disease severity in CF patients. The distribution of FccRIIA genotypes was not significantly different between CF patients and controls. We observed that in CF patients with the same CFTR genotype (DF508/DF508), those carrying the R allele of FccRIIA had an increased risk of acquiring chronic P. aeruginosa infection (P ¼ 0.042, R.R.: 4.38; 95% CI: 1.17C22.4). Moreover, the frequency of R/R genotype in patients with chronic P. aeruginosa infection seems to be higher than that of control subjects and patients without chronic infection. The observation that CF patients carrying the R allele of FccRIIA are at higher risk of acquiring chronic P. aeruginosa infection suggests that the FccRII loci genetic variation is contributing to this infection susceptibility.

Identification of Therapeutic Targets for Quiescent, Chemotherapy-Resistant Human Leukemia Stem Cells

“…As expected, CD32- and CD25-null mice showed deficiencies in myeloid and lymphoid development (32–35). In humans, allelic variants of FCGR2A have been associated with susceptibility to systemic lupus erythematosus and to bacterial infections in certain populations (36–38). These findings are attributed to differential function of phagocytes bearing the particular polymorphisms.…”

Update on gene modifiers in cystic fibrosis

“…Published studies have examined mostly immune or inflammatory genes, including ACE [19,20], ADRβ2 [20–23], ATB 0 [24], CAPN10 [25], ClCN2 [26], DEFβ4 [27], ENaC [28], FcβRII [29], GCLC [30], GSTM1 [20,31–35], GSTM3 [34], GSTP1 [20,33–35], GSTT1 [34], HFE [36,37], HLA-I [38], HLA-II [38–41], HLA-III [38], HSP70 [39], IFN-γ [19], IL1-β [39], IL6 [25], IL10 [19,20,42], IL18 [25], KCNJ11 [25], MBL2 [20,43–52,53 •• ], MIF [54], NOS1 [55–57], NOS3 [20,58], MASP-2 [48,51], PPARβ [25], SERPINA1 [20,59–67], SERPINA3 [68], SFTPA1 [50], SFTPA2 [50], TLR4 [69], TGFB1 [19,20,52,53 ββ ,67,70–72 •• ,73 •• ], TNFα [19,20,25,32,52,74–76], TNFα -receptor [28], and TNFβ [39]. …”

“…To date several gene–gene interactions have been reported between CFTR and modifier genes, including GCLC [30], MBL2 [49,50], FCγRII [29], NOS1 [55], and TGFβ1 [19,73 •• ]. Most of these reported gene– CFTR interactions demonstrate the presence of or increased variant polymorphism effects in the context of ΔF508 or other severe mutation homozygosity, excepting the GCLC – CFTR interaction and the TGFB1 – CFTR interaction as reported by Bremer et al Other reported gene–gene interactions in CF include MBL2 – TGFB1 [53 •• ], TNF •-8.1 ancestral MHC genotype [75], and GSTM1 – GSTP1 [35].…”

Parental knowledge and behaviour to prevent environmental P. aeruginosa acquisition in their children with CF

“…Little is known about factors which could protect the CF host against chronic infection. The patient's genetic background may play a role [7][8][9], or the ability to produce opsonophagocytic antibodies against PA [10].…”