Increased HbF levels or F-cell (HbF containing erythrocyte) numbers can ameliorate the disease severity of β-thalassemia major and sickle cell anemia. Recent genome wide association studies reported that single nucleotide polymorphisms (SNPs) in BCL11A gene on chromosome 2p16.1 were correlated with F-cells among healthy northern Europeans, and HbF among Sardinians with β-thalassemias. In this study, we showed that SNPs in BCL11A were associated with F-cell numbers in Chinese with β-thalassemia trait, and with HbF levels in Thais with either β-thalassemia or HbE trait and in African Americans with sickle cell anemia. Taken together, the data suggest that the functional motifs responsible for modulating F-cells and HbF levels reside within a 3 kb region in the second intron of BCL11A.

Toxocara canis, Toxocara cati, are roundworms that live in the intestines of dogs and cats, respectively, and are predominantly agents of human toxocariasis. Studies have suggested that Toxocara spp. seroprevalence increases levels of total and aeroallergen-specific IgE (sIgE), asthma prevalence and asthma morbidity. Nevertheless, other work reported a negative association between Toxocara spp. seropositivity with skin hypersensititity and a positive association with sIgE. The objective of the present study was to evaluate risk factors for acquiring Toxocara spp. infection and to investigate possible significant association between its seroprevalence with atopy and asthma. Students from elementary schools, residents in a small town and its surroundings of Northeast Brazil, underwent blood sampling to measure levels of anti-Toxocara spp. IgG, peripheral blood eosinophils, and specific IgE to aeroallergens. We used univariable and multivariable logistic regression analyses to assess possible risk factors for Toxocara spp. seropositivity and its association with atopy, wheeze/asthma with asthma phenotypes, in a sample of 791 elementary school children aged 6-13 years. Toxocara spp. seroprevalence reached 63.6%; 49.9% had sIgE; 7.2% and 3.3% had atopic wheeze/asthma and non-atopic wheeze/asthma respectively. Risk factors associated with Toxocara spp. seropositivity were: contact with dogs (adj. OR 2.33; 95% CI=1.70-3.19) and cats (adj. OR 3.09; 95% CI=2.10-4.55), and male sex (adj. OR 2.21; 95% CI=1.62-3.02). The presence of anti-Toxocara IgG was statistically associated with blood eosinophils >4% and >10% (adj. OR 1.84; 95% CI=1.33-2.55 and adj. OR 2.07; 95% CI=1.45-2.97, respectively), and atopy (adj. OR 2.00; 95% CI=1.49-2.68), but it was not associated with wheeze/asthma. Concluding, the results obtained in this study showing the association of Toxocara spp. seroprevalence with sIgE may suggest a possible immunological cross-reactivity between IgE epitopes from Toxocara spp. and aeroallergens.

Sickle cell anemia (SCA) is a disorder characterized by a heterogeneous clinical outcome. In the present study, we investigated the associations between Tumor Necrosis Factor-alpha (TNF-alpha) -308G>A and Interleukin 8 (IL-8) -251A>T gene polymorphisms, medical history and classical biomarkers in children with steady-state SCA. In total, 210 SCA patients aged 2-21 years and 200 healthy controls were studied. Gene polymorphisms, betaS-globin haplotypes and a 3.7-kb deletion in alpha2-thalassemia (α2-thal3.7 kb) were investigated by PCR/RFLP analysis, and cytokine levels were determined by ELISA. Splenomegaly (p=.032) was more prevalent among children younger than 5 years of age. The A allele of the TNF-alpha -308G>A gene polymorphism and the presence of α2-thal3.7 kb were associated with an increase risk of splenic sequestration events (p=.001; p=.046), while the T allele of the IL-8 -251A>T gene polymorphism was considered to be a protective factor for splenomegaly events (p=.032). Moreover, the A allele of the TNF-alpha -308G>A gene polymorphism was associated with high TNF-alpha levels (p=.021), and the hemoglobin F and hemoglobin S haplotypes were correlated with serum levels of IL-8. The logistic regression analysis showed significant effects of the TNF-alpha and IL-8 gene polymorphisms, beta(S)-globin gene haplotypes and α2-thal3.7 kb on the occurrence of splenic sequestration events. Our study emphasizes that the identification of new genetic and immunological biomarkers and their associations with classical markers is an important strategy to elucidate the underlying causes of different SCA phenotypes and their effects on patient outcome.

Sickle cell anemia (SCA) is a genetically inherited hemolytic disorder characterized by chronic inflammation. Cytokine expression affects the pivotal pathways that contribute to disease pathogenesis, but the mechanisms involved are not well understood. SCA is associated with a proinflammatory state, and an enhanced inflammatory response occurs during vasoocclusive crisis. The immune system thus plays an important role in this inflammatory condition, with several cell types secreting pro-inflammatory cytokines that contribute to the occurrence of common cyclical events in SCA patients, such as hemolysis, vascular occlusion and inflammation. Studies of these cytokines and chemokines in SCA patients have clarified the mechanisms that underlie this disease and highlighted the need for a better understanding of cytokine participation in SCA pathophysiology.

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