The present study is a contribution to the definition of the linkage disequilibrium relationship of MICA and MICB with adjacent loci and to the characterization of extended HLA haplotypes. These issues are of importance for the identification of disease associations and for a better definition of donor-recipient compatibility in bone-marrow grafts through the typing of haplospecific markers. The distribution of the five alleles of MICA and the 13 alleles of MICB microsatellites, located, respectively, in MICA transmembrane exon 5 and in MICB intron 1, was examined in 133 healthy Italian individuals previously typed for HLA class I, class II and complement loci and for the TNFa microsatellite. The MICB microsatellite was also analysed in 49 HTCLs for which MICA typing was already available. Very strong linkage disequilibria with HLA-B and TNFa were detected in the Italian population for both MICA and MICB microsatellite alleles, in spite of the high mutability rate of the larger MICB alleles. Some strong associations were also detected between MICB and DRB1. The strongest associations (P < 0.001, D' > 0.7) were those of MICA-A4 with HLA-B18, B27 and TNFa1, MICA-A5 with HLA-B35, B61 and B62, MICA-A5.1 with HLA-B7, B8, B13, B63 and MICB-CA24, MICA-A6 with HLA-B51, MICA-A9 with HLA-B39, B57 and TNFa2, MICB-CA14 with HLA-B14, B27 and TNFa1, MICB-CA15 with HLA-B52, TNFa4 and TNFa13, MICB-CA17 with HLA-B7 and TNFa11, MICB-CA18 with HLA-B13 and TNFa7, MICB-CA22 with HLA-B57, and MICB-CA24 with HLA-B8 and TNFa2. From pairwise associations in the random panel and results for the homozygous cell lines it was possible to deduce the MICA and MICB microsatellite alleles present in many of the well-known Caucasoid extended haplotypes.

The aim of the present study was to compare different techniques of HLA antibody detection in patients waiting for a transplant. Two methods of HLA antibody screening were compared: the complement-dependent cytotoxicity (CDC) test and the enzyme-linked immunosorbent solubility assay (ELISA). Three different commercial kits for the latter assay were tested: the kits were produced by One Lambda (O.L.) and SANG STAT for prescreening and specificity determination, and GTI only for prescreening. Of the two techniques, only CDC can detect IgM. The study included 207 serum samples selected from 192 patients waiting for a first kidney transplant. The conclusions are that O.L. is more sensitive than CDC and the other ELISA kits and is much faster for analysing a serum (taking only a few hours), but costs about 16 times more than CDC and does not detect IgM antibodies, so can be used only in support of CDC.

We observed that a match for class I and class II HLA antigens apparently does not favor the long-term survival of transplanted kidneys. In fact, matched grafts are lost before 10 years in the same proportion as the mismatched grafts. We also demonstrated (1) that patients who are homozygous for GG at the SNP -1082IL10 (high IL-10 producers) and HLA class I mismatched (but matched for class II) are protected from chronic rejection, and (2) that patients who are homozygous for CC at the SNP -33IL4 (low IL-4 producers) and HLA class I mismatched (regardless of matching for class II) are protected from chronic rejection.

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Ninety patients on dialysis, 241 cadaveric kidney donors and 27 cadaveric kidney recipients with a follow-up of 2 years, have been investigated as for anti-HCV positivity by means of 3 tests. As for patients on dialysis and cadaveric donors, the prevalence was 32 and 4%, respectively. As for transplanted patients, it must be noted that 4 negative recipients from positive donors seroconverted, but without any change in hepatic enzymes, while in 2 or 9 anti-HCV-positive recipients, hepatic enzymes increased after transplantation. Seroconversion in patients transplanted from a negative donor was not significantly different. We conclude that, according to their experience, anti-HCV positivity in the donors is not associated with a significant risk of infection in recipients of cadaveric grafts.