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Human leukocyte antigen (HLA)-G is upregulated on the bronchial epithelium of asthma patients and genetic polymorphism affecting expression of HLA-G has been reported to influence susceptibility to asthma. As the NK cell receptor KIR2DL4 has been reported to induce interferon gamma (IFNγ) secretion when ligated with HLA-G, we postulated that the 9A/10A genetic polymorphism of KIR2DL4 which influences receptor structure may influence susceptibility to asthma. KIR2DL4 genotypes were determined in two cohorts of children (n = 219 and n = 1356) in whom total serum IgE, allergen-specific IgE, atopy, bronchial reactivity and asthma symptoms had been studied between birth and 14 years. No reproducible associations with KIR2DL4 genotype were identified, leading us to conclude that the KIR2DL4 9A/10A polymorphism has no influence on susceptibility to asthma.

The aim of this study was to determine whether a common diabetic haplotype, including human leukocyte antigen (HLA)-B8 and HLA-DR3, in Northern India is the same haplotype as the European HLA-B8-DR3 haplotype. DNA samples from Northern Indian subjects selected on the basis of HLA-B8 and HLA-DR3 were tested for microsatellite and single nucleotide polymorphism alleles throughout the major histocompatibility complex (MHC). It was found that the Indian samples represent a conserved haplotype in which all alleles were shared by Indian subjects with HLA-B8 and HLA-DR3, but were different to those that are characteristic of the European 8.1 ancestral haplotype. The Indian and European haplotypes share HLA-B*0801, HLA-DRB1*0301 and HLA-DQB1*02 but differ for subtypes of HLA-Cw*07 and HLA-DRB3 and all central MHC alleles tested. In contrast, Indian subjects selected on the basis of HLA-B58 ( 1-17) and HLA-DR3 shared the same alleles at other MHC loci as have been described in the common Chinese haplotype with HLA-B58/17 and HLA-DR3. A third haplotype, HLA-B50/21 and HLA-DR3, was also found to be highly conserved but shares little in common with the other two HLA-DR3-containing Indian haplotypes.

Single-stranded conformation polymorphism (SSCP) by capillary electrophoresis was assessed as a screening and typing method for alleles of KIR2DL4. Exon 6 was investigated as this exon was reported to include three polymorphic nucleotides. Exon 6, intron 6 and exon 7 were amplified as a single polymerase chain reaction (PCR) product of 650 bp from genomic DNA. The PCR product was sequenced and analysed by SSCP. Exon 7 was found to be invariant. Only two nucleotides were found to be polymorphic in exon 6 and another three were found in intron 6. Strong linkage disequilibrium was found between the polymorphic nucleotides resulting in the presence of three alleles in a panel of 20 cell lines. Two alleles differed within intron 6 while the third allele differed at two nucleotides in exon 6. All six possible genotypes were distinguishable by SSCP providing information from both the forward and reverse primers was used. Exon 6 of one allele was one nucleotide shorter than that of the other alleles and the resulting frame shift is predicted to produce a truncated cytoplasmic tail due to a premature stop codon four codons into exon 7. SSCP was found to be an efficient method of typing exons 6 and 7 in a panel of 46 bone marrow donors. All three alleles were found to be common and one was in strong linkage disequilibrium with the presence of another KIR sequence KIR3DS1.

The killer cell immunoglobulin-like receptors (KIR) are a family of receptors expressed on natural killer (NK) cells and some T cells. Class I HLA molecules on target cells are the ligands for the KIR receptors. The number of KIR genes has been reported to vary between individuals, resulting in different KIR haplotypes. There is little published data on the frequency of each KIR gene and the linkage disequilibrium between the genes. Because there is evidence that NK cells may be involved in bone marrow transplant rejection, we have determined the KIR gene frequencies and possible haplotypic arrangements by linkage disequilibrium analysis in an Australian population.Controls, patients with leukemia, and unrelated bone marrow donor-recipient pairs were typed for the presence of 11 KIR genes by polymerase chain reaction-sequence specific priming.Ninety percent of the population was found to have a sufficient number and variety of KIR genes to detect any mismatch of HLA-A, -B, and -C alleles on NK target cells. The 11 KIR genes could be divided into two groups based on linkage disequilibrium between pairs of genes. Evidence for a recombination within the KIR gene complex is presented.Typing for the presence of particular KIR genes may be indicated for bone marrow donor-recipient pairs for whom a class I HLA mismatch is unavoidable.

Periodontal attachment loss is mediated by overproduction of tumour necrosis factor (TNF) and interleukin (IL)-1, and appears to have a genetic component. The 8.1 major histocompatibility complex (MHC) ancestral haplotype (HLA-A1,B8,TNFA-308(2),DR3) is associated with elevated TNF production and predisposes carriers to several autoimmune/immunopathological disorders, including rapid progression of HIV disease, but not early onset periodontal disease in healthy individuals. Rather a high proportion of subjects with severe periodontal disease carry allele 2 at IL-1A-889 and IL-1B+3953. We predicted that genetic associations may be different or clearer in HIV patients, as they often show elevated production of TNF and IL-1 and periodontal attachment loss. Hence periodontal parameters and IL-1 polymorphisms were assessed in HIV-positive subjects expressing HLA-B8 with or without other markers of the 8.1 haplotype. Of 16 HLA-B8 subjects, 13 demonstrated elevated probing pocket depth and clinical attachment loss. The difference was statistically significant and did not correlate with smoking, age, CD4 T-cell counts, HIV viral load or levels of dental plaque. As TNFA-308 (allele 2) was present in four non-B8 subjects who had minimal attachment loss, it may not mediate the effect of the 8.1 haplotype. Moreover, polymorphisms at IL-1A-889 and IL-1B+3953 did not significantly affect periodontal parameters. Thus a central MHC gene characteristic of the 8.1 haplotype was the clearest determinant of periodontal attachment loss in HIV-infected individuals.

To determine whether the MHC plays an antigen non-specific role in the development of acute GVHD, the prevalence of acute GVHD in relation to MHC genotype was examined in 51 adult patients undergoing allogeneic BM grafting. The majority of patients received grafts from HLA-identical siblings. HLA-B7 haplotypes were associated with a decreased risk of acute GVHD (2 of 15, p = 0.005) whereas HLA-B44 haplotypes were associated with a higher risk of acute GVHD (11 of 14, p = 0.02). As these alleles have been reported previously as having opposite effects in relation to inflammatory mediators, these findings may have important implications with respect to donor selection and patient management.

The immune response of pneumonia patients and controls to Streptococcus pneumoniae was investigated by enzyme-linked immunosorbent assay (ELISA). Patients less than 6 months of age had significantly lower levels of anti-pneumococcal polysaccharide antibodies than their age-matched controls. Patients and controls 6-14 months of age had lower antibody levels than the children 0-5 months of age. Adult patients and controls did not differ in their antibody status. However, patients and Papua New Guinean controls had depressed cell-mediated immunity and low T-cell numbers. Low levels of antibodies to pneumococcal polysaccharides in children less than 6 months of age appear to be an important risk factor for acute lower respiratory tract infections but other factors may be important in older infants and adults.The immune response of pneumonia patients and controls to Streptococcus pneumoniae was investigated by enzyme-linked immunosorbent assay (ELISA). Patients under 6 months of age had significantly lower levels of anti-pneumococcal polysaccharide antibodies than their age-matched controls. Patients and controls ages 6-14 months had lower antibody levels than children ages 0-5 months. Adult patients and controls did not differ in their antibody status. However, patients and Papua New Guinean controls had depressed cell-mediated immunity and lower T-cell numbers. Low levels of antibodies to pneumococcal polysaccharides in children less than 6 months of age appear to be an important risk factor for acute lower respiratory tract infections but other factors may be important in older infants and adults.

Immune function was studied in Papua New Guinea highland infants with pneumonia, healthy highland controls and expatriate controls under the age of 15 months. Delayed-type hypersensitivity to tuberculin was depressed in highland pneumonia patients and highland controls as were CD4/CD8 T-lymphocyte ratios. The differences between highland and expatriate infants were more pronounced after 6 months of age, suggesting an environmental effect. Serum immunoglobulin and complement concentrations were higher in highland infants than in expatriate controls. Indices of nutritional status were similar in highland and expatriate infants but iron deficiency was more common in the highland infants in the study.17 highland Papua New Guinean infants (PNG) and 19 expatriate infants were matched with 20 0-14 month old infants from the highlands with moderate or severe pneumonia admitted to the Goroka Hospital in the Eastern Highlands Province of Papua New Guinea to evaluate their immune systems to determine the factors that may affect their ability to begin and maintain an effective immune response. Both the PNG controls and patients tended not to respond to a delayed-type hypersensitivity challenge with tuberculin, especially the 6-14 month old infants. Specifically, all of the expatriate 6-14 month old infants responded while only 3 of the 8 PNG controls and 2 of the 10 pneumonia patients did. Moreover the CD4/CD8 lymphocyte ratios for the PNG controls were significantly lower than those of the expatriate controls for both the O-5 and 6-14 month old infant groups (p.02), but especially in the 6-14 month group. In addition, both the PNG controls and patients exhibited more iron deficiency than the expatriates (p.02), again especially among the 6-14 month old infants. Other nutritional status indices were the same in both PNG and expatriate controls. The differences in PNG controls were more extreme in the patients. These findings suggested that cell-mediated immunity is depressed in Papua New Guinea. On the other hand, infants humoral immune systems were very active. The difference in delayed-type hypersensitivity and CD4/CD8 ratios was larger in the 6-14 month old group than in the 0-5 month old group, suggesting than an environmental effect had a gradual influence on cell-mediated immunity. Since cytomegalovirus (CMV) infection occurs early in life in developing countries, increases CD8 lymphocyte numbers, and may induce temporary diminished reactivity to specific antigens, it was hypothesized that CMV may be the environmental effect.

Lymphocyte subsets were enumerated in Papua New Guinean children, adolescents and adults from the Eastern Highlands and comparative groups of age-matched expatriates living in the Goroka area. From the age group under 6 months until adolescence, the numbers and percentages of CD8-positive (suppressor/cytotoxic) T cells were higher in Papua New Guinean highlanders than in expatriates. In highland subjects over 35 years of age, both CD8-positive and CD4-positive (helper/inducer) T-cell numbers were lower than in younger subjects whereas in expatriates their numbers remained the same. Highlanders over the age of 35 years had fewer T cells (including CD8-positive T cells) than expatriates. Helper/suppressor ratios were lower in highlanders than in expatriates from the age group under 6 months to the 20-30 year age group; the lowest ratio was found at 10-15 years of age, when the mean was 0.95.

A serological assay for C. pylori would be more convenient than gastric biopsy tests. A variety of ELISA assays for C. pylori have been reported, the sensitivities and specificities vary considerably [1]. Some groups have satisfactorily used crude antigen extracts of C. pylori while others report a high rate of false positive reactions. We have been impressed by the bimodal serology produced by crude antigen extracts and have undertaken an evaluation of an ELISA based on this extract taking into account the results of microbiological culture, microscopy, urease tests and the degree of inflammation in the the biopsy.

Fractures of the fifth metatarsal are fairly frequent. Articles and texts offer conflicting advice concerning treatment and prognosis of these fractures. By proper classification of these fractures and understanding of the mechanism of injury, a criterion can be established for the prognosis and treatment.

Many authors believe that osteochondritis occurs more frequently in the medial sesamoid than in the lateral. The authors of this paper discuss three cases of fibular sesamoid fracture in adolescents that they believe have progressed secondarily to osteochondritis.