CpG-oligodeoxynucleotides inhibit RSV-enhanced allergic sensitisation in guinea pigs.

Experimental respiratory syncytial virus (RSV) infection of guinea pigs is associated with enhanced allergic sensitisation to inhaled ovalbumin (OA) and low-level viral persistence in the lungs. Based on the T-helper (Th)1/Th2 paradigm, in which a Th2 shift is characteristic of an allergic response and less effective anti-viral immunity, the effects of immunotherapy with synthetic cytosine phosphate-guanine-oligodeoxynucleotides (CpG-ODN), which are potent Th1 stimuli, on OA sensitisation with and without RSV infection were evaluated. Measurements included quantitative histology for airway inflammation by T-cells and eosinophils, semiquantitative RT-PCR for lung Th1/Th2 balance (interferon (IFN)-gamma/interleukin (IL)-5 mRNA ratios), and serology for circulating titres of OA-specific immunoglobulin (Ig)G1 antibodies. RSV antigens were identified in lung tissue sections by immunohistochemistry. CpG-ODN immunotherapy did not prevent OA sensitisation of guinea pigs; however, in RSV-infected, OA-sensitised animals, CpG-ODN administration was associated with significant reductions of airway T-cells and eosinophils, increased lung IFN-gamma/IL-5 ratios, and decreased OA-specific IgG1 antibody titres to levels observed in uninfected, OA-sensitised animals. Viral antigens were identified in a similar proportion of the lungs of RSV-infected animals, irrespective of CpG-ODN immunisation status. In conclusion, cytosine phosphate-guanine-oligodeoxynucleotides immunotherapy protects guinea pigs against respiratory syncytial virus-enhanced ovalbumin sensitisation and might be a relevant intervention in the context of post-bronchiolitis allergic sensitisation in children.

Hb Lulu Island (alpha 2 beta 2 107[G9]Gly-->Asp)-beta zero- thalassemia (codon 15; TGG-->TAG), a form of thalassemia intermedia.

Hb Lulu Island [beta 107(G9)Gly-->Asp] was discovered in an East Indian female who carried a common beta zero-thalassemia allele, i.e., codon 15, TGG-->TAG (is a stop codon) in trans. Both abnormalities were detected through sequencing of the amplified beta-globin genes and were confirmed by hybridization with 32P-labeled probes. Hb Lulu Island is mildly unstable with a borderline decrease in oxygen affinity; its instability is less severe than that of Hb Burke or beta 107(G9)Gly-->Arg. The compound heterozygosity expresses as a thalassemia intermedia with moderate anemia, a variable need for blood transfusions, Heinz body formation, and a red cell morphology which is typical for such a condition. The level of HbA2 was greatly increased (6.5-7.0%) as was the delta chain level (12% of total non-alpha) probably because of the instability of Hb Lulu Island and the decreased ability of the beta x chain to form dimers with the normal alpha chain.