Clinical immunology
Predilection to sepsis, acute tissue infections and delayed infected wound healing may depend on genetic polymorphisms

Most published studies on infections and patients’ genetic polymorphisms are dealing with sepsis. Only few analyze the genetic predilection to less fulminant inflammatory processes as acute circumscribed organ or tissue infections and infections causing delayed healing of large wounds. There is only a quantitative difference between these three conditions in the host immune reaction regulated by the same mechanism, thus, the genetic basis should be common. We decided to study the polymorphisms of selected allele of cytokines and TLRs at 9 polymorphic sites in randomly selected groups of patients displaying symptoms of sepsis, acute tissue infections and prolonged wound suppuration. Our study provided the following observations: 1) in the entire group of patients presenting systemic and local infections, we found higher frequency of tumour necrosis factor  (TNF-) G308A GG, TNF- G525A mutated homozygote AA, and CCR2 G190A mutated homozygote AA than in controls (all p < 0.0001). At the TGF- G25C site there was a low expression of GG compared with the controls (p < 0.001). 2) comparison of subgroups of sepsis, acute tissue infections and delayed infected wound revealed more of CD14 C-159T CT, TLR1.2 C2259A GA and C2029T CT in sepsis than other infections but the differences were not significant. There was lack of differences in the subgroups in expression of TNF- G308A GG , TNF- G525A heterozygote GA, CCR2 G190A AA, TLR4.1 A1036G AA and TLR4.2 C1336T CC. 3) TNF- serum levels were higher in all patients compared to controls. The highest values of TNF- were seen in G308A GA genotypes. They were high in cases with sepsis and acute infections. The TGF- serum level was not higher in the whole group of patients with infection than in controls, however, in subgroups of sepsis and acute infections increased values were found in T941C CC genotype. Taken together, polymorphism of TNF- and TNF-, CD14, TLR2.1, CCR2 and TGF- genes at certain mutation points may be predisposing to surgical type of infections. No significant differences in investigated polymorphisms were found between sepsis, acute local tissue infections and delayed infected wound healing.