The accumulation of highly sensitized patients (HSP) on renal transplant waiting lists is a problem faced by all transplant registries. We have studied the HLA class I serological reactivity of 20 random HSP and have related antibody specificity to primary amino acid sequence. In six patients we identified significant correlations (chi 2 test, r > or = 0.93) between panel reactivity and specific amino acid substitutions characteristic of HLA-A, -B, and -C public epitopes. Antibody reactivity was associated with up to three public epitopes in each patient. The 12 separate antibody specificities identified were associated with 10 residues. Seven correlated with HLA-A locus substitutions (Glu-62/Gly-65, Lys-66, Arg-114, His-114/Tyr-116/Lys-127, Thr-142/His-145 [x2], and Thr-149), two with HLA-B locus substitutions (Thr-24, Ser-24) and three with interlocus antibodies associated with either HLA-A and B (Leu-82/Arg-83 [x2]) or with HLA-B and -C substitutions (Leu-163). This information allowed us to predict HLA class I allelic products of known primary sequence that would react negatively with each HSP serum. Windows of acceptable mismatches (WAMMs) can thus be delineated with a view to crossmatch negative transplantation without the need for exhaustive serological analysis. Surprisingly we found that WAMMs for these patients included up to 80% of the 10 commonest HLA class I haplotypes in the British population with four patients being crossmatch compatible with A1,3; B7,8. These observations lead us to propose a more intelligent approach to transplanting HSP based on epitope analysis and definition of WAMMs.

1.1) Analysis of nonreactivity in FRA lymphocytotoxicity assays allows the identification of ‘acceptable mismatches’.2.2) A few amino acid substitutions seem to account for 75% and 90% PRA in the sera from two patients, GH and ML.3.3) When the ‘acceptable mismatches’ of GH and ML were aligned against the ten most common HLA-A, B haplo-types in the UK, half were judged ‘acceptable’.4.4) In view of the ample opportunity for sensitization to two of these antigens (HLA-B7 and -B8) through a previous kidney rejected by GH these data suggest the existence of some form of programmed nonresponsiveness to common phenotypes.5.5) The tendency for recipient selection schemes to siphon off kidneys with common HLA phenotypes for beneficially matched nonsensitized recipients discriminates against HSPs.6.6) The imagined risk of transplanting kidneys with acceptable mismatches should prove groundless if nonreactivity can be clearly shown to be attributed to energy or tolerance.

In a Preliminary study we have shown that optimally collected human umbilical cord [HUC] blood cells grow significantly better in long term cultures [LTC] than normal adult marrow cells [NBM] p=0.0007. The LTC findings are supported by the observation in clonogenic assay that a similar number of GM-CFC colonies can be grown from HUC blood and NBM mononuclear cells [MNC]. Also there is a trend towards a higher proportion of primitive erythroid [BFU-E] and primitive megakaryocyte colonies [MK-CFC containing >20 cells] in HUC blood compared with NBM. We suggest that further work on the feasibility of a HLA typed, cryopreserved HUC blood bank as a source of unrelated haemopoietic 'stem' cells for clinical transplantation is indicated.

On December 6th, 1989, Sir Jack Hibbert opened a discussion meeting at the Royal Statistical Society (RSS) on Public Confidence in the Integrity and Validity of Official Statistics. Several speakers suggested a UK National Statistical Commission could alleviate some of the perceived problems with official statistics. An RSS Working Party (whose membership was announced at the meeting) examined, inter alia, the merits of such a Commission and one of its recommendations in its July 1990 report was that the UK should set up a National Statistical Commission. As a basis for a fuller discussion of the Working Party's recommendation for a UK National Statistical Commission, this short paper outlines the role, construction and operation of similar Commissions in various countries, putting forward a possible model for such a Commission in the UK.