Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients' and donors' HLA-C allotypes was evaluated in multivariable models. Increasing expression level of the patient's mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient's mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease

Bilateral and unilateral mixed lymphocyte culture (MLC) tests were performed in five families, each containing one sibling in which recombination between the genes determining the antigens of the LA and Four segregant series of IIL-A had occurred. The results confirm the very weak or non-stimulatory effect of antigens of the LA segregant series, bringing t o seven the total number of alleles for which this has been shown so far. Further anomalies in one of the families, however, indicate that the antigens of the Four segregant series are not fully responsible for MLC activation either. Of a group of three HL-A identical siblings, one proved t o be MLC-positive with the other two, but MLC-negative with another group of two HL-A identical siblings, which group displayed a one-allelic difference for HL-A with the former group. Furthermore, the child showing this unexpected MLC reaction pattern proved also t o be MLC-negative with the earlier mentioned sibling who had the serologically demonstrable recombination between the LA and Four series, notwithstanding a difference for three HL-A antigens.These findings are interpreted as strong evidence for the occurrence of a recombination between the HL-A loci and a MLC determining locus, which can thus be localize outside the previously recognized HL-A region close t o the Four locus. The relationships between HL-A, MLC, skin graft rejection and organ transplantation are reexamined in the light of this concept.

Five novel missense mutations, viz., C304 A, T370 G, G484 A, G667 A, and G808 A, in the Lewis gene (FUT3) were detected in African (Xhosa) and Caucasian individuals in South Africa. These single base substitutions may result in changes in amino acid residues from Gln102 to Lys in the 304 mutation, Ser124 to Ala in the 370 mutation, Asp162 to Asn in the 484 mutation, Gly223 to Arg in the 667 mutation, and Val270 to Met in the 808 mutation. Out of the five novel mutations identified in this investigation, four new alleles (le484,667, le484,667,808, Le304, and Le370) were determined in the Xhosa population and two new alleles (le202,314,484 and Le304) in the Caucasian population. The determination of alpha(1,3/1,4)fucosyltransferase activity, after transfection of plasmids containing the new alleles into COS7 cells, suggested that alleles le484,667 and le484,667,808 encoded an inactive enzyme, and that alleles Le304 and Le370 encoded a functional enzyme. In addition, we also examined the incidence of five common alleles, Le59, le59,508 le59,1067, le202,314, and le1067 in two populations by the polymerase chain reaction/restriction fragment length polymorphism method and compared differences in the allele frequencies of FUT3 among three ethnic groups (Orientals, Africans, and Caucasians).

Objective: To determine the nutritional status and household resources of preschool children. Design: A cross-sectional survey. Setting: Two informal settlement areas, Joe Slovo (JS) and JB Mafora (JBM) in Mangaung, near Bloemfontein, South Africa. Subjects: Preschool children (,72 months) of a randomly selected sample of households in JS (experimental) (n = 162) and JBM (control) (n = 186) were included. Standard methods were used to obtain household and care-giver particulars, weight and height measurements, blood and stool samples, and 24-hour dietary recalls. Results: Breast-feeding and dietary intake in the two areas were nearly similar; breastfeeding was continued for 12 months and longer. Although the children's total protein intake was suf®cient, their energy intake was low. A low median intake of micronutrients prevailed, including iron, zinc, calcium, niacin, ribo¯avin, thiamine and vitamins C, B 6 , A and D. The prevalence of being underweight (JS = 19.8%; JBM = 18.8%), stunted (JS = 29%; JBM = 21.5%) and wasted (JS = 6.5%; JBM = 3.7%) were fairly similar in both areas, as well as the prevalence of marginal vitamin A de®ciency, anaemia, iron de®ciency and parasite infestations. No signi®cant associations could be found between household and nutritional status indicators, probably due to the small number of well-nourished children and the generally poor household situation of the participants. Conclusions: The generally poor nutritional status and environmental conditions emphasize the urgency of intervention for these children.

The HLA-A10 crossreacting group consists of the A25, A26, A34, A43 and A66 antigens. Here, we report allelic sequences for A43 and for 2 subtypes of both A26 and A34. Combining these results with previously determined sequences for A25, A26 and A66 enables molecular comparison of all the serologically defined A10 antigens. They form a closely related and well-defined group of alleles which may have originated with A*2601. Patterns of serological crossreactivity are correlated with sequence and a public epitope shared by A33 and members of the A10 family is localized to residues R62 and N63. The A*2501, A*4301 and A*6601 alleles appear to have derived from A*2601 by single gene conversion events with other HLA-A alleles. In the case of A*4301, the donor allele was probably an A29 allele as A*4301 has a small element of sequence in the alpha 1 helix (residues L62 and Q63) uniquely shared with A29. The chimaeric structure of A43 explains the reactivity of A43 molecules with both A10 and A29 alloantisera. The rare Oriental variant of A26 (A26v*) is encoded by an allele (A*2602) that differs from A*2601 by a unique nucleotide substitution which changes aspartate to asparagine at position 116 in the floor of the peptide binding groove. Thus A*2602 is a functionally distinct allele that originated by a point mutation. Alleles encoding A34 and A66 antigens are found to have very similar structures, explaining the difficulty in their serological definition.(ABSTRACT TRUNCATED AT 250 WORDS)