Coassociations between IL10 polymorphisms, IL-10 production, helminth infection, and asthma/wheeze in an urban tropical population in Brazil.

BACKGROUND: Helminth infections are associated with protection against allergies. It is postulated that IL-10 production after helminth infection suppresses skin hypersensitivity and increases IgG4 production, protecting against allergies. OBJECTIVE: We aimed to determine whether IL10 polymorphisms are associated with helminth infection and the risk of wheeze and allergy. METHODS: Twelve IL10 single nucleotide polymorphisms were genotyped in 1353 children aged 4 to 11 years living in a poor urban area in Salvador, Brazil. Wheezing status, Ascaris lumbricoides and Trichuris trichiura infection, IL-10 production by peripheral blood leukocytes stimulated with A lumbricoides extract, serum total IgE levels, specific IgE levels, skin prick test responses to common aeroallergens, and IgG4 and IgE anti-A lumbricoides antibody levels were measured in all children. Association tests were performed by using logistic or linear regression when appropriate, including sex, age, helminth infection, and principal components for ancestry informative markers as covariates by using PLINK. RESULTS: Allele G of marker rs3024496 was associated with the decreased production of IL-10 by peripheral blood leukocytes in response to A lumbricoides stimulation. Allele C of marker rs3024498 was negatively associated with helminth infection or its markers. Marker rs3024492 was positively associated with the risk of atopic wheeze, total IgE levels, and skin prick test responses to cockroach. CONCLUSIONS: Our findings suggest that IL10 polymorphisms might play a role in the production of IL-10, helminth infection, and allergy. We hypothesize that polymorphisms related to protection against helminths, which would offer an evolutionary advantage to subjects in the past, might be associated with increased risk of allergic diseases.

IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population.

BACKGROUND: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. AIMS: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. METHODS: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. RESULTS: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 × 10(-5) ). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 × 10(-3) ). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 × 10(-3) ), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 × 10(-3) and P = 2.16 × 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 × 10(-3) ); Amerindian and European ancestry genetic contribution were greater in the SVR group. CONCLUSION: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.

Natural killer cell receptor and HLA-C gene polymorphisms among patients with hepatitis C: a comparison between sustained virological responders and non-responders.

BACKGROUND/AIMS: Killer cell immunoglobulin-like receptors (KIR) are involved in the activation/inhibition of NK cells through an interaction with HLA class I molecules on target cells. Our study aimed to evaluate the association between KIR gene polymorphisms and the response of patients with CHC to antiviral therapy. METHODS: We compared the frequency of KIR genes, as well as that of compound KIR/HLA-C genotypes, between groups of patients with CHC who presented a sustained virological response (n=66) and who were non-responders to a combination of pegylated or standard interferon and ribavirin (n=101). KIR and HLA-C genotyping were performed using commercial kits. RESULTS: We detected a greater frequency of the KIR2DL5 gene among non-responders to antiviral therapy compared with sustained virological responders (68.3 vs. 40.9%) (P<0.001). We used multiple logistic regression analysis to determine the association between therapy response and the presence of KIR2DL5, after a control for potentially confounding variables (genotype, alcohol, fibrosis, gender, age, ethnic background and route of HCV infection). The results confirmed the strong association between the presence of KIR2DL5 and the non-response to antiviral treatment (P=0.001). CONCLUSIONS: Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.

The metabolic syndrome in Spanish migrants to Brazil: unexpected results.

A cross-sectional study was performed involving epidemiological and clinical features of the metabolic syndrome (MS) in Spanish migrants to Brazil and their descendants. This included 479 subjects: Group A (Spanish migrants): n=215; Group B (descendants born in Brazil of Spanish parents): n=126, Group C (mixed descendants born in Brazil with either father or mother born in Spain): n=138. MS was defined according to the original NCEP/ATP III criteria and by the revised NCEP/ATP definition (glucose>or=100mg/dl). Overall prevalence of MS according to NCEP/ATP III criteria was 26.3%. Age/sex-adjusted prevalence was 27.4%. When the revised NCEP criteria were considered, overall prevalence was 30.1% (age/sex-adjusted 31.3%). The differences between the two criteria were 3.8% and 3.9% (CI -1.9-9.4%). When stratified by groups the MS was more prevalent in Group A (37.2%) and Group B (20.6%) than in Group C (10.9%). Environmental factors may have influenced the development of MS. Reason for the apparently protective role of genetic features due to admixture between populations in the mixed descendants needs to be explored.

Antibodies to Schistosoma mansoni in human cerebrospinal fluid.

Cerebrospinal fluid (CSF) and serum samples from patients suspected of having neuroschistosomiasis (NS) were evaluated by an enzyme-linked immunosorbent assay. Monoclonal antibodies of various immunoglobulin isotypes (IgM, IgA, IgE, total IgG, IgG1, IgG2, IgG3, and IgG4) were used to detect antibodies against Schistosoma mansoni soluble egg antigen (SEA) and soluble worm adult preparation (SWAP). Of the 83 CSF samples tested, 55% were reactive to SEA (26% were reactive only to SEA and 29% to both SEA and SWAP), 34% were reactive to SWAP (5% only to SWAP and 29% to both SEA and SWAP), and 40% were not reactive with any antigen. Cases that tested positive for SWAP in CSF and negative in serum were not found. Samples with high specific IgG antibody titers were selected for immunoglobulin isotype profiling. In the CSF samples, the antibodies against SEA and SWAP were mainly IgM, IgG1, and IgG4, although other immunoglobulins were also detected. Interestingly, nine patients had high levels of IgG1 only in the CSF. These results suggest that there is local synthesis of IgG1, and that this isotype could be an important immunologic marker in the diagnosis of NS.

Effect of soy protein supplementation in patients with chronic hepatitis C: a randomized clinical trial.

AIM: To evaluate the effects of soy supplementation on insulin resistance, fatty liver and alanine aminotransferase (ALT) levels in non-diabetic patients with chronic hepatitis C (CHC). METHODS: In a prospective, randomized and single-blinded clinical trial, we compared patients with CHC who had casein as a supplement (n = 80) (control group), with patients who consumed a soy supplement diet (n = 80) [intervention group (IG)]. Both groups received 32 g/d of protein for 12 wk. RESULTS: Patients' baseline features showed that 48.1% were overweight, 43.7% had abdominal fat accumulation, 34.7% had hepatic steatosis and 36.3% had an homeostasis model assessment index of insulin resistance (HOMA-IR) ≥ 3.0. Descriptive analysis showed that protein supplementation diet reduced hepatic steatosis in both groups; however, significant reductions in ALT levels occurred in the soy group. Multiple regression modeling indicated that in the presence of severe fibrosis (F3/F4), γ glutamyl transferase elevation and high density lipoprotein (HDL) reduction, the intervention group had 75% less chance of developing hepatic steatosis (OR= 0.25; 95% CI: 0.06-0.82) and 55% less chance of presenting with an ALT level ≥ 1.5 × the upper limit of normal (ULN) (OR = 0.45, 95% CI: 0.22-0.89). Soy treatment did not have any effect on insulin resistance (OR = 1.92; 95% CI: 0.80-4.83), which might be attributed to the fact that the HOMA-IR values at baseline in most of our patients were in the normal range. Advanced hepatic fibrosis, an ALT level > 1.5 × ULN and visceral fat were predictors of an HOMA-IR ≥ 3. The IG group had a reduced risk of an ALT level > 1.5 × ULN. An HOMA-IR ≥ 3.0 and HDL < 35 mg/dL were also risk factors for increased ALT. CONCLUSION: Soy supplementation decreased ALT levels and thus may improve liver inflammation in hepatitis C virus (HCV) patients; it also reduced hepatic steatosis in a subgroup of patients but did not change insulin resistance. It should be considered in the nutritional care of HCV patients.

HLA class II polymorphism in Brazilian populations

A investigação da distribuição e freqüência dos genes HLA (Human Leukocyte Antigens) em populaçõespresumivelmente saudáveis é importante para avaliar a participação desses genes na susceptibilidadee proteção a doenças, para avaliar a origem genética das populações e para auxiliar na realização detransplantes. Os avanços na biologia molecular têm permitido um melhor entendimento desse sistema. Além disso, informações sobre as moléculas HLA de classe II, tais como seu mecanismo de ação, função e polimorfismo genético têm colocado esse sistema como marcador da composição das populações. Os genes HLA de classe II parecem ser associados a alguns grupos étnico-raciais mais que a outros. Usando essas características genéticas, é possível demonstrar, por exemplo, o grau de mistura de caucasianos, africanos e ameríndios que contribuem, de modo significante, para a origem da população brasileira, bem como esclarecer alguns aspectos da ancestralidade dessas populações, o que ajuda na realização de estudospopulacionais com o objetivo de obter informações sobre a história, formação, migração e composição de grupos populacionais de acordo com suas peculiaridades locais. Esse tema assume relevância em virtude da freqüência dos antígenos, alelos e haplótipos HLA de classe II na população brasileira.