No abstract

Air pollution and subsequent increased oxidative stress have long been recognized as contributing factors for asthma phenotypes. Individual susceptibility to oxidative stress is determined by genetic variations of the antioxidant defence system. In this study, we analysed the association between environmental nitrogen dioxide (NO 2 ) exposure and single nucleotide polymorphisms (SNP) in NFE2L2 and KEAP1 genes and their common impact on asthma risk.We genotyped 12 SNPs in a case-control study of 307 patients diagnosed with asthma and 344 controls. NO 2 concentration was collected from the period preceding the development of asthma symptoms. Multiple logistic regression was applied to evaluate the effects of the studied genetic variations on asthma outcomes in interaction with NO 2 exposure. Our data showed that genotypes of rs2588882 and rs6721961 in the regulatory regions of the NFE2L2 gene were inversely associated with infection-induced asthma (odds ratio (OR)00.290, p00.0015, and OR00.437, p0 0.007, respectively). Furthermore, case-only analyses revealed significant differences for these SNPs between asthma patients that lived in modestly or highly polluted environment , p 00.01, and OR 0 0.51, p00.02, respectively, in a dominant model). In conclusion, our results throw some new light upon the impact of NFE2L2 polymorphisms on infection-induced asthma risk and their effect in gene-environment interactions.

SUMMARYWe have examined the effect of two i,v. itnmunoglobulin preparations on the metabolic and funclional activities of neuirophil granulocyles from the peripheral blood. Production of superoxide anion (O;) by granulocytes was measured through superoxide dismutase inhibitable reduction of ferricytochrome C after incubalion of cells for various times together with immunoglobulin (concenlration ranging from 025 lo 50 mg/ml). The results showed dose-dependent response of O; production independent ofthe incubation lime. Granulocytes containing ingested Staphytococcus aureus released a signlfieanlly (f < 0 001) larger amounl of O; and killed a higher number {F < 0 001) of viable bacteria in ihe presence of 5 mg/ml immunoglobulin than did cells incubated in the absence of extracellular i.v. immunoglobulin. These data raise Ihe possibility that immunoglobulin concentrates for i.v. use may enhance the anti-bacterial activities of phagocytic cells through direct stimulation ofthe respiratory burst. Infiammatory reactions observed during i.v. immunoglohulin infusion in hypo-or agammaglobulinaemic patients may also be related to phagocytic cell activation.

Diagnosis of immunoglobulin deficiency with increased IgM (hyper-IgM syndrome) was made in three siblings (two girls and a boy) on the basis of history, physical findings, and laboratory data. The prominent clinical findings were recurrent viral and bacterial infections of the respiratory tract. The most severe infections affected the male patient, who died at the age of 8 years. Family history and the lack of clinical signs in the parents and relatives indicated no immunodeficiency which, together with the occurrence of the disease in both sexes, indicated an autosomal recessive inheritance. The two female patients (18 years old and 3 years old) have been treated with intravenous acid-treated immunoglobulin for 2 years, resulting in significant clinical improvement with respect to the frequency and severity of infections.

SUMMARY Thirteen infants with staphylococcal sepsis and reduced opsonic activity received infusions of acid treated immunoglobulin together with antibiotics. Opsonic activity (using Staphylococcus aureus (type 42D) as the test organism), haemolytic activity of complement, and concentrations of complement C3 and IgG were measured in serum prepared before and after three days of treatment with immunoglobulin at a dose of 250-300 mg/kg/day. There was increased ingestion of S aureus by normal human granulocytes in the presence of fresh serum prepared after infusion of immunoglobulin and significantly increased opsonic activity of heat inactivated serum after treatment with immunoglobulin. The haemolytic activity of complement and concentrations of complement C3 were not influenced, and serum concentrations of IgG increased as the result of receiving a total of 800-900 mg/kg immunoglobulin over a period of three days. This study shows that administration of acid treated IgG to septic infants leads to functionally increased opsonisation.