No abstract

Kawasaki disease is an acute multisystem vasculitic syndrome of unknown etiology occurring mostly in infants and children younger than 5 years of age. In developed countries, Kawasaki disease is currently the leading cause of acquired heart diseases in children. However, it is still a mysterious disease. In this article, we reviewed and summarized from the aspects based on infection agents, host immune dysregulation and genetic background intended to establish a feasible infection-immunogenetic pathogenesis for this mysterious disease and also provided the rational strategy to explore optimal treatment of this disease.

Rationale: Little is known about effects of paternal tobacco smoke (PTS) on the offspring’s asthma and its prenatal epigenetic programming. Objective: To investigate whether PTS exposure was associated with the offspring’s asthma and correlated to epigenetic CG methylation of potential tobacco-related immune genes: LMO2, GSTM1 or/and IL-10 genes. Measurements and Main Results: In a birth cohort of 1,629 newborns, we measured exposure rates of PTS (23%) and maternal tobacco smoke (MTS, 0.2%), cord blood DNA methylation, infant respiratory tract infection, childhood DNA methylation, and childhood allergic diseases. Infants with prenatal PTS exposure had a significantly higher risk of asthma by the age of 6 than those without ( p = 0.026). The PTS exposure doses at 0, <20, and ≧20 cigarettes per day were significantly associated with the trend of childhood asthma and the increase of LMO2-E148 ( p = 0.006), and IL10_P325 ( p = 0.008) CG methylation. The combination of higher CG methylation levels of LMO2_E148, IL10_P325 , and GSTM1_P266 corresponded to the highest risk of asthma by 43.48%, compared to other combinations (16.67–23.08%) in the 3-way multi-factor dimensionality reduction (MDR) analysis. The LMO2_P794 and GSTM1_P266 CG methylation levels at age 0 were significantly correlated to those at age of 6. Conclusions: Prenatal PTS exposure increases CG methylation contents of immune genes, such as LMO2 and IL-10 , which significantly retained from newborn stage to 6 years of age and correlated to development of childhood asthma. Modulation of the LMO2 and IL-10 CG methylation and/or their gene expression may provide a regimen for early prevention of PTS-associated childhood asthma. Descriptor number: 1.10 Asthma Mediators. Scientific Knowledge on the Subject : It has been better known that maternal tobacco smoke (MTS) has an impact on the offspring’s asthma via epigenetic modification. Little is known about effects of paternal tobacco smoke (PTS) on the offspring’s asthma and its prenatal epigenetic programming. What This Study Adds to the Field : Prenatal tobacco smoke (PTS) can program epigenetic modifications in certain genes, such as LMO2 and IL-10 , and that these modifications are correlated to childhood asthma development. The higher the PTS exposure dose the higher the CG methylation levels are found. The combination of higher CG methylation levels of LMO2_E148, IL10_P325 and GSTM1...

Allergic mechanism has long been attributed to IgE‐mediated reaction. The relationship between gene polymorphism and cord blood IgE (CB IgE) is unclear. We investigated whether elevation of CB IgE levels was associated with polymorphisms of cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) at (−318) CT and (+49) AG positions in a gender‐limited fashion. CB IgE levels were determined by Pharmacia CAP system and the CTLA‐4 polymorphisms at (−318) and (+49) were determined by restriction fragment length polymorphism (RFLP). A total of 644 consecutive umbilical cord bloods were collected for this study. 32.9% of newborn infants had detectable IgE levels (≥0.35 kU/l). 25.6% of the male newborns had elevated CB IgE levels (≥0.5 kU/l) similar to those of the female newborns (22.7%). The CTLA‐4 polymorphism at (+49) but not (−318) was significantly associated with elevated CB IgE levels (p = 0.004). The association of CTLA‐4 (+49) A allele with elevated CB IgE levels was found only in females. Both male and female infants with different CTLA‐4 (−318) genotypes had no difference in the rates of elevated CB IgE levels. A linkage disequilibrium between CTLA‐4 (+49) G and (−318) C allele was found in this Chinese population. Subjects with the (+49, GG and −318, CC) genotype had a significantly lower rate of elevated CB IgE levels. Association of the CTLA‐4 (+49) polymorphism with elevated CB IgE levels was found only in female infants. Newborn infants with the (+49, GG and −318, CC) genotype tended to have a low rate of elevated CB IgE.

Background: Allergic diseases are thought to be inherited. Prevalence of allergic diseases has, however, increased dramatically in last decades, suggesting environmental causes for the development of allergic diseases.Objective: We studied risk factors associated with the development of atopic dermatitis (AD), allergic rhinitis (AR) and asthma (AS) in children of non-atopic parents in a subtropical country.Methods: In a birth cohort of 1,497 newborns, parents were prenatally enrolled and validated for allergic diseases by questionnaire, physician-verified and total or specific Immunoglobulin E (IgE) levels; 1,236 and 756 children, respectively, completed their 3-year and 6-year follow-up. Clinical examination, questionnaire, and blood samples for total and specific IgE of the children were collected at each follow-up visit.Results: Prevalence of AD, AR and AS was, respectively, 8.2%, 30.8% and 12.4% in children of non-atopic parents. Prevalence of AR (p<.001) and AS (p=.018) was significantly higher in children of parents who were both atopic. A combination of Cesarean section (C/S) and breastfeeding for more than 1 month showed the highest risk for AD (OR=3.111, p=.006). Infants living in homes with curtains and no air filters had the highest risk for AR (OR=2.647, p<.001), and male infants of non-atopic parents living in homes without air filters had the highest risk for AS (OR=1.930, p=.039).Conclusions: Breastfeeding and C/S affect development of AD. Gender, use of curtains and/or air filters affect AR and AS, suggesting that control of the perinatal environment is necessary for the prevention of atopic diseases in children of non-atopic parents.