The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses.

Food allergy has increased dramatically in prevalence over the past decade in westernized countries, and is now a major public health problem. Unfortunately for patients with food allergy, there is no effective therapy beyond food allergen avoidance, and rapid medical treatment for accidental exposures. Recently, oral immunotherapy (OIT) has been investigated as a treatment for this problem. In this review, we will discuss the progress in developing OIT for food allergy, including a novel approach utilizing Xolair (anti-IgE monoclonal antibody, omalizumab) in combination with OIT. This combination may enhance both the safety and efficacy of oral immunotherapy, and could lead to a widely available and safe therapy for food allergy.

Over the last four decades, monumental advances have been made in the understanding, assessment, and management of transfusion-dependent patients, which have translated into significant improvements in patient morbidity and mortality. Important lessons have been learned from extensive clinical experience of iron management in the thalassemias, but greater knowledge of key differences in the sickle-cell disease (SCD) population may impact on our approach to patient assessment and management. The unique pathophysiology of SCD is reflected in a distinct pattern of iron loading with minimal organ-specific injury. An appreciation and understanding of these differences should allow us to develop tailored management approaches that optimize patient outcomes.

A 21-year-old male with sickle cell disease (SCD) presented with severe pallor. He had received a total of 100 red blood cell (RBC) units in his lifetime, had a mean serum ferritin level of 3133 ng/ml, and liver iron concentration (LIC) of 12 mg Fe/g dry weight (dw). He was started on subcutaneous deferoxamine (DFO) infusions at a dose of 56 mg/kg/d, five days a week (equivalent to 40 mg/kg/d, seven days a week) and continued to receive 8-10 RBC units/year as treatment for pain. During the first six months of chelation therapy, his serum ferritin levels fell by around 50% of the pretreatment value, but then started to increase back up to the baseline values. The patient was noncompliant with DFO therapy. He experienced pain at the site of injection, could not sleep and was concerned about carrying a pump and not being accepted by his peers. He dropped out of college and abstained from all social activities. He was referred to a psychologist; however, this failed to improve compliance and he opted to stop DFO therapy altogether.The role of iron chelation therapy has long been acknowledged in the management of iron overload in patients receiving blood transfusion therapy; however, data specific to the treatment of patients with SCD are limited. DFO (Desferal 1 ; Novartis Pharma AG, Basel, Switzerland) was the first iron chelator to be licensed, more than 40 years ago, for chronic iron overload as a result of transfusion-dependent anemia and remains the current reference standard iron chelator. The efficacy and safety of DFO is well established in patients with b-thalassemia major [1-3]; however, clinical evaluation in SCD-specific populations is limited. Early small-scale studies of transfused patients with SCD showed that DFO was able to increase urinary iron excretion [4,5] and intensive chelation regimens in heavily iron-overloaded patients with SCD showed acceptable efficacy and safety [6][7][8]. In these small-scale studies, there were no reported incidences of impaired hearing or visual acuity, toxicities that have been noted in patients with b-thalassemia major and other rare anemias when doses are inappropriately high for the level of iron overload [9]. However, careful regulation of dosage and regular audio-visual monitoring is still advised. Increased zinc excretion demonstrated at very high DFO doses (180 mg/kg) [8] may lead to extreme zinc deficiency in patients with SCD who may already have decreased plasma zinc levels [10]. The verification of possible adverse events specific to patients with SCD most certainly requires further study.The major limitation of DFO is the requirement for frequent, slow parenteral administration, which can be painful and inconvenient. Compliance has a noticeable impact on a patient's response to therapy and can have serious consequences, as described in this case. In patients with b-thalassemia major, the demands of DFO therapy have been shown to have a negative impact on quality of life and mental health [11]. The impact of infusions may be greatest for adolescents and y...